Claude Meistelman

Vecuronium neuromuscular blockade at the diaphragm, the orbicularis oculi, and adductor pollicis muscles

To determine the relationship among diaphragm, orbicularis oculi, and adductor pollicis blockade, train-of-four stimulation was applied to the phrenic, facial, and ulnar nerves in 16 adult patients anesthetized with alfentanil-propofol-oxygen. Vecuronium 0.04 or 0.07 mg/kg was given. The response of the adductor pollicis was measured with a force transducer, and that of the other muscles by electromyography (EMG). No statistically significant differences were detected with either dose in the intensity of maximum blockade measured at the three muscles. With 0.04 mg/kg, the first response (T1) in the train-of-four was decreased (mean +/- SEM) 78 +/- 8, 62 +/- 11, and 84 +/- 3% for the diaphragm, orbicularis oculi, and adductor pollicis, respectively. Corresponding values after 0.07 mg/kg were 95 +/- 3, 82 +/- 11, and 95 +/- 2%, respectively. However, onset time was longer at the adductor pollicis than at the diaphragm, and the orbicularis oculi onset time approached that of the diaphragm. With 0.04 mg/kg, time to maximum diaphragmatic blockade was 2.9 +/- 0.3 min, compared with 3.7 +/- 0.6 min at the orbicularis oculi (no significant difference [NS]) and 6.6 +/- 0.4 min at the adductor pollicis (P less than 0.001). With vecuronium 0.07 mg/kg the values were 2.2 +/- 0.3, 3.4 +/- 0.5 (P = 0.024), and 6.3 +/- 0.6 (P less than 0.001), respectively. Time to 75% T1 recovery was similar at the diaphragm and the orbicularis oculi, but significantly longer at the adductor pollicis.(ABSTRACT TRUNCATED AT 250 WORDS)

Vecuronium neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis

The differences between neuromuscular blockade of the adductor muscles of the vocal cords and the adductor pollicis were examined in 20 adult women anesthetized with fentanyl and propofol. Vecuronium 0.04 or 0.07 mg/kg was given as a single bolus by random allocation. The force of contraction of the adductor pollicis was recorded. Laryngeal response was measured as pressure changes in the cuff of the tracheal tube positioned between the vocal cords. Train-of-four stimulation was applied to the recurrent laryngeal nerve at the notch of the thyroid cartilage and to the ulnar nerve at the wrist. Neuromuscular blockade had a faster onset, was less intense, and recovered more rapidly at the vocal cords. With 0.04 mg/kg, maximum blockade of first twitch (T1) was 55 +/- 8 (mean +/- standard error of the mean [SEM]) and 88 +/- 4% at the vocal cords and the adductor pollicis, respectively (P = 0.006). Onset time was 3.3 +/- 0.1 and 5.7 +/- 0.2 min, respectively (P = 0.000001), and time to 90% T1 recovery was 11.3 +/- 1.6 and 26.1 +/- 1.8 min, respectively (P = 0.001). With 0.07 mg/kg, onset time was unchanged; maximum blockade was more intense, being 88 +/- 4 and 98 +/- 1%, respectively (P = 0.04 between muscles); and time to 90% T1 recovery was 23.3 +/- 1.8 min at the vocal cords versus 40.3 +/- 2.9 min at the adductor pollicis (P = 0.001). Approximately 1.73 times as much vecuronium was required at the larynx compared with the dose required at the adductor pollicis for the same intensity of blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Rocuronium (ORG 9426) neuromuscular blockade at the adductor muscles of the larynx and adductor pollicis in humans.

The effects of rocuronium, 0.25 or 0.5 mg · kg, were measured simultaneously on the adductor muscles of the larynx and adductor pollicis in 14 adult patients. Anaesthesia was induced and maintained with propofol and fentanyl. Tracheal intubation was performed without muscle relaxants. The recurrent laryngeal and ulnar nerves were both stimulated supramaximally, at the notch of the thyroid cartilage and at the wrist respectively, using train-of-four stimulation. The laryngeal response was evaluated by measuring the pressure change in the cuff of a tracheal tube positioned between the vocal cords. Onset time, intensity of blockade and duration of action were less at the larynx than at the adductor pollicis. After rocuronium, 0.25 mg · kg−1, the onset time (interval between injection and maximal TI blockade) was 1.6 ± 0.1 min and 3.0 ± 0.3 min (mean ± SEM) at the laryngeal muscles and adductor pollicis, respectively (P < 0.01 between muscles). Maximum blockade was 37 ± 8% and 69 ± 8%, respectively (P < 0.05), and time to 90% TI recovery was 7 ± 1 min and 20 ± 4 min, respectively (P < 0.05). With 0.5 mg· kg−1, the onset time was also more rapid at the vocal cords (1.4 ± 0.1 min) than at the adductor pollicis (2.4 ± 0.2 min, P < 0.001). Maximum blockade was 77 ± 5% and 98 ± 1 %, respectively (P < 0.01), and time to 90% TI recovery was 22 ± 3 min and 37 ± 4 min, respectively (P < 0.01). It is concluded that with rocuronium onset and recovery are faster at the laryngeal adductor muscles, but blockade is less intense than at the adductor pollicis. These findings are similar to the observations made previously with vecuronium, except that rocuronium had a faster onset at both muscles.RésuméLe but de cette étude était de mesurer chez 14 sujets adultes l’effet du rocuronium, 0.25 ou 0.5 mg · kg−1, à la fois sur les muscles adducteurs du larynx et sur l’adducteur du pouce. L’induction et l’entretien de l’anesthésie se sont effectés à l’aide de propofol et de fentanyl. On n’a pas utilisé de curare pour l’intubation trachéale. On a appliqué une stimulation supramaximale en train-de-quatre à l’échancrure du cartilage thyroïde, pour le nerf récurrent laryngé, et au poignet, pour le nerf cubital. La contraction des muscles laryngés produisait un changement de pression dans le ballonnet de la sonde trachéale, placé entre les cordes vocales. Le temps d’installation, le bloc maximum et la durée d’action étaient moindres au niveau du larynx qu’à l’adducteur du pouce. Après injection de 0.25 mg · kg−1 de rocuronium, le temps d’installation (intervalle entre l’injection et bloc maximum de TI) etait de 1.6 ± 0.1 et de 3.0 ± 0.3 min (moyenne ± écart type de la moyenne) pour les muscles laryngés et l’adducteur du pouce, respectivement (P<0,01 entre les muscles). Le bloc maximum se situait à 37 ± 8 et 69 ± 8%, respectivement (P < 0,05), et on comptait 7 ± 1 et 20 ± 4 min respectivement (P < 0,05) jusqu’ à un retour de TI à 90%. Avec une dose de 0.5 mg · kg−1, le temps d’installation était aussi plus court pour les cordes vocales (1.4 ± 0.1 min) que pour l’adducteur du pouce (2.4 ± 0.2 min, P < 0.001). On retrouvrait un bloc maximum de 77 ± 5 et 98 ± 1%, respectivement, et une durée d’action jusqu’á une récupération de TI à 90% de 22 ± 3 et 37 ± 4 min respectivement (P < 0,01). On en conclut que le rocuronium agit plus rapidement au niveau des muscles adducteurs du larynx, mais que le bloc neuromusculaire est moins intense qu’au niveau de l’adducteur de pouce. Ces résultats sont comparables à ceux obtenus avec le vècuronium, sauf que le rocuronium agit plus rapidement au niveau des deux muscles.

Can acceleromyography detect low levels of residual paralysis? A probability approach to detect a mechanomyographic train-of-four ratio of 0.9

Background: The incidence of residual paralysis, i.e., a mechanomyographic train-of-four (TOF) ratio (T4/T1) less than 0.9, remains frequent. Routine acceleromyography has been proposed to detect residual paralysis in clinical practice. Although acceleromyographic data are easy to obtain, they differ from mechanomyographic data, with which they are not interchangeable. The current study aimed to determine (1) the acceleromyographic TOF ratio that detects residual paralysis with a 95% probability, and (2) the impact of calibration and normalization on this predictive acceleromyographic value. Methods: In 60 patients, recovery from neuromuscular block was assessed simultaneously with mechanomyography and acceleromyography. To obtain calibrated acceleromyographic TOF ratios in group A, the implemented calibration modus 2 was activated in the TOF-Watch S®; to obtain uncalibrated acceleromyographic TOF ratios in group B, the current was manually set at 50 mA (n = 30 for each). In addition, data in group B were normalized (i.e., dividing the final TOF ratio by the baseline value). The agreement between mechanomyography and acceleromyography was assessed by calculating the intraclass correlation coefficient. Negative predictive values were calculated for detecting residual paralysis from acceleromyographic TOFs of 0.9, 0.95, and 1.0. Results: Group A: For a mechanomyographic TOF of 0.9 or greater, the corresponding acceleromyographic TOF was 0.95 (range, 0.86–1.0), and the negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 37% (95% CI, 20–56%), 70% (95% CI, 51–85%), and 97% (95% CI, 83–100%), respectively. Group B: Without normalization, an acceleromyographic TOF of 0.97 (range, 0.68–1.18) corresponded to a mechanomyographic TOF of 0.9 or greater, with negative predictive values for acceleromyographic TOFs of 0.9, 0.95, and 1.0 being 40% (95% CI, 23–59%), 60% (95% CI, 41–77%), and 77% (95% CI, 58–90%), respectively. After normalization, an acceleromyographic TOF of 0.89 (range, 0.63–1.06) corresponded to a mechanomyographic TOF of 0.9 or greater, and the negative predictive values of acceleromyographic TOFs of 0.9, 0.95, and 1.0 were 89% (95% CI, 70–98%), 92% (95% CI, 75–99%), and 96% (95% CI, 80–100%), respectively. Conclusion: To exclude residual paralysis reliably when using acceleromyography, TOF recovery to 1.0 is mandatory.

Monitoring the onset of neuromuscular block at the orbicularis oculi can predict good intubating conditions during atracurium-induced neuromuscular block.

This study was designed to assess whether monitoring the orbicularis oculi (OO) can predict good tracheal intubating conditions.Fifty patients, ASA grade I or II were studied. Anesthesia was induced with thiopental (5 mg/kg) and fentanyl (3 micro gram/kg). The ulnar and facial nerves were simultaneously stimulated using train-of-four (TOF) stimulations every 10 s. The responses of the adductor pollicis (AP) and the OO were estimated visually. Patients were randomly allocated to receive either atracurium 0.5 mg/kg (n = 30) or 0.3 mg/kg (n = 20). In each group, endotracheal intubation was performed randomly when the OO or the AP was completely blocked. If complete block was not obtained, intubation was performed 300 s after administration of atracurium. Intubating conditions were scored on a 1 to 4 scale. All intubations were performed by the same physician unaware of the dose and the muscular responses. After 0.5 mg/kg, both muscles were completely blocked in all patients. The average onset time (time from the injection of atracurium to the disappearance of all muscular responses after TOF) was shorter at the OO (2.35 +/- 0.12 min) than at the AP (3.59 +/- 0.15 min) (P < 0.001) (mean +/- SD). Endotracheal intubating conditions were comparable in both groups: good or excellent after 0.5 mg/kg. After 0.3 mg/kg, complete block was achieved only 2/20 at the OO and 12/20 at the AP. Intubating conditions were comparable in both groups: poor or inadequate, except in the two patients with complete OO block, for whom conditions were good. It is concluded that OO monitoring can predict good intubating conditions earlier than AP monitoring when using 0.5 mg/kg but not 0.3 mg/kg atracurium. (Anesth Analg 1995;80:360-3)

Antagonism of low degrees of atracurium-induced neuromuscular blockade: dose-effect relationship for neostigmine.

Background:Low degrees of residual paralysis (i.e., a train-of-four [TOF] ratio > 0.4) are relatively frequent, difficult to detect, and still potentially harmful. Unfortunately, the appropriate dose of anticholinesterase for this situation has not been determined. This may be of clinical interest because a high dose of neostigmine given at a shallow level of neuromuscular block may produce neuromuscular weakness. The purpose of this study was to investigate the dose–effect relationship of neostigmine to antagonize residual paralysis corresponding to a TOF ratio of 0.4 and 0.6. Methods:Recovery after 10, 20, 30 &mgr;g/kg neostigmine or placebo given at either 0.4 or 0.6 TOF ratio was assessed by acceleromyography in 120 patients undergoing intravenous anesthesia. Time to a 0.9 and 1.0 TOF ratio was measured, and the probability of successful reversal within 10 min after the respective neostigmine doses was calculated. In addition, the dose of neostigmine needed to achieve the recovery targets in 5 or 10 min was also determined. Results:When given at a TOF ratio of either 0.4 or 0.6, time to 0.9 and 1.0 TOF ratio was significantly shorter with any dose of neostigmine than without. The probability of successful reversal after 20 &mgr;g/kg neostigmine was 100% when a TOF ratio of 0.9 was the target; for a TOF ratio of 1.0, the probability was 93% and 67%, dependent on whether the dose of neostigmine was given at TOF ratio of 0.6 or 0.4, respectively. With a dose of 30 &mgr;g/kg, a TOF ratio of 1.0 is expected to be reached within approximately 5 min. Low doses of neostigmine are required to reach a TOF ratio of 0.9 or to accept an interval of 10 min. Conclusion:Reduced doses (10–30 &mgr;g/kg) of neostigmine are effective in antagonizing shallow atracurium block. For successful reversal within 10 min, as little as 20 &mgr;g/kg neostigmine may be sufficient. These dose recommendations are specific for atracurium and an intravenous anesthetic background.

Neuromuscular effects of succinylcholine on the vocal cords and adductor pollicis muscles.

To quantify the effects of succinylcholine at the laryngeal adductor muscles and the adductor pollicis, 17 adult patients were studied during propofol-fentanyl anesthesia. Train-of-four stimulation was applied to the ulnar nerve at the wrist and the recurrent laryngeal nerve at the notch of the thyroid cartilage. Laryngeal response was measured as pressure changes in the cuff of the tracheal tube positioned between the vocal cords. The force of contraction of the laryngeal adductor muscles and of the adductor pollicis were compared after administration of 0.25 or 0.5 mg/kg of succinylcholine. With 0.25 mg/kg, maximum blockade of first twitch (T1) was 66% ± 10% (mean ± SEM) and 45% ± 13% at the vocal cords and the adductor pollicis, respectively (P < 0.01). After 0.5 mg/kg, maximum blockade at the vocal cords (93% ± 2%) and the adductor pollicis (84% ± 6%) did not differ significantly. For both doses, time to maximal blockade was shorter for the vocal cords (0.9 ± 0.1 min) than for the adductor pollicis (1.7 ± 0.2 min; P < 0.01). Time to 90% recovery of T1 after a bolus of 0.5 mg/kg was similar at the vocal cords (4.3 ± 0.5 min) and the adductor pollicis (5.2 ± 0.8 min) (NS). The ED50 was less at the laryngeal adductors (0.170 mg/kg) than at the adductor pollicis (0.278 mg/kg). It is concluded that, in adults, succinylcholine-induced blockade is more rapid and more intense at the laryngeal muscles than at the adductor pollicis.

Lipopolysaccharide-Induced Increase of Prostaglandin E2 Is Mediated by Inducible Nitric Oxide Synthase Activation of the Constitutive Cyclooxygenase and Induction of Membrane-Associated Prostaglandin E Synthase

NO produced by the inducible NO synthase (NOS2) and prostanoids generated by the cyclooxygenase (COX) isoforms and terminal prostanoid synthases are major components of the host innate immune and inflammatory response. Evidence exists that pharmacological manipulation of one pathway could result in cross-modulation of the other, but the sense, amplitude, and relevance of these interactions are controversial, especially in vivo. Administration of 6 mg/kg LPS to rats i.p. resulted 6 h later in induction of NOS2 and the membrane-associated PGE synthase (mPGES) expression, and decreased constitutive COX (COX-1) expression. Low level inducible COX (COX-2) mRNA with absent COX-2 protein expression was observed. The NOS2 inhibitor aminoguanidine (50 and 100 mg/kg i.p.) dose dependently decreased both NO and prostanoid production. The LPS-induced increase in PGE2 concentration was mediated by NOS2-derived NO-dependent activation of COX-1 pathway and by induction of mPGES. Despite absent COX-2 protein, SC-236, a putative COX-2-specific inhibitor, decreased mPGES RNA expression and PGE2 concentration. Ketoprofen, a nonspecific COX inhibitor, and SC-236 had no effect on the NOS2 pathway. Our results suggest that in a model of systemic inflammation characterized by the absence of COX-2 protein expression, NOS2-derived NO activates COX-1 pathway, and inhibitors of COX isoforms have no effect on NOS2 or NOS3 (endothelial NOS) pathways. These results could explain, at least in part, the deleterious effects of NOS2 inhibitors in some experimental and clinical settings, and could imply that there is a major conceptual limitation to the use of NOS2 inhibitors during systemic inflammation.

Comparison of twitch depression of the adductor pollicis and the respiratory muscles : pharmacodynamic modeling without plasma concentrations

BackgroundAlthough the respiratory muscles (the diaphragm and the laryngeal adductors) recover from paralysis more rapidly than does the adductor pollicis, patients can develop complete paralysis of the respiratory muscles, but not of the adductor pollicis, after bolus administration of vecuronium. The authors used a pharmacodynamic model not requiring muscle relaxant plasma concentrations to reconcile these findings. MethodsThe pharmacodynamic model is based on the traditional model, in which: (1) vecuronium concentration at the neuromuscular junction (Ceffect) is a function of the plasma concentration versus time curve and a rate constant for equilibration between plasma and the neuromuscular junction (kco); and (2) effect is a function of Ceffect, the steady-state plasma concentration that produces 50% effect (C50), and a factor to explain the sigmoid relationship between concentration and effect. In the absence of vecuronium plasma concentrations, an empiric model (rather than the usual effect compartment model) can be used to mimic the time delay (proportional, but not identical, to 1/kco) between dose and effect. The model can be used to estimate the steady-state infusion rate that produces 50% effect (IR50), equal to the product of C50 and vecuronium plasma clearance; IR50 for different muscle groups then can be compared to assess relative sensitivity. The authors applied this model to published effect data for subjects given 40–70 μg/kg vecuronium in whom paralysis of three muscle groups was measured during opioid/propofol anesthesia. ResultsFor IR50, the ratio of values for the larynx:diaphragm:adductor pollicis was 1.4:1.2:1; for the equilibration constant (inversely proportional to the time delay), the ratio for the respiratory muscles to the adductor pollicis was 2.5:1. ConclusionsVecuronium concentrations peak earlier at the respiratory muscles than at the adductor pollicis, possibly the result of greater perfusion to these organs, leading to earlier onset of paralysis. The observation that bolus injection of vecuronium produces greater paralysis of the respiratory muscles than of the adductor pollicis, despite greater resistance of the respiratory muscles, can be explained by differential rates of equilibration between plasma and various muscles.

A Method to Measure Elicited Contraction of Laryngeal Adductor Muscles during Anesthesia

The recurrent laryngeal nerve was stimulated with surface electrodes to produce vocal cord adduction, and the response was measured as pressure changes in the inflatable cuff of a tracheal tube positioned between the vocal cords. To test the linearity of the system, a model of the larynx consisting of a syringe barrel was constructed, and weights were applied to two bands of tissue simulating the vocal cords. Tests on Mallinckrodt size-7.5 tubes showed that the pressure increase produced by a given force was independent of baseline pressure in the range 10-30 mmHg. In addition, the pressure inside the inflatable cuff was linear with increasing weight (or force) for a baseline pressure of 10 mmHg. Thirty ASA physical status 1 or 2 adults were anesthetized with propofol and fentanyl. Tracheal intubation was performed in the absence of muscle relaxants, and the inflatable cuff of the tracheal tube was positioned between the vocal cords. Pressure inside the cuff was measured with an air-filled transducer. Stimulation was produced at different sites along the course of the recurrent laryngeal nerve. A surface electrode placed over the notch of the thyroid cartilage produced consistent adduction of the cords, measured as an increase of 8.9 +/- 5.1 mmHg (mean +/- standard deviation [SD]) in the cuff pressure. Neuromuscular blocking drugs produced train-of-four fade, and large doses abolished the response completely, ruling out direct muscle stimulation. It is concluded that this assembly can provide useful information on intrinsic laryngeal muscle function.