Background Management of acute respiratory failure by noninvasive ventilation is often associated with asynchronies, like autotriggering or delayed cycling, incurred by leaks from the interface. These events are likely to impair patient’s tolerance and to compromise noninvasive ventilation. The development of methods for easy detection and monitoring of asynchronies is therefore necessary. The authors describe two new methods to detect patient–ventilator asynchronies, based on ultrasound analysis of diaphragm excursion or thickening combined with airway pressure. The authors tested these methods in a diagnostic accuracy study. Methods Fifteen healthy subjects were placed under noninvasive ventilation and subjected to artificially induced leaks in order to generate the main asynchronies (autotriggering or delayed cycling) at event-appropriate times of the respiratory cycle. Asynchronies were identified and characterized by conjoint assessment of ultrasound records and airway pressure waveforms; both were visualized on the ultrasound screen. The performance and accuracy of diaphragm excursion and thickening to detect each asynchrony were compared with a “control method” of flow/pressure tracings alone, and a “working standard method” combining flow, airway pressure, and diaphragm electromyography signals analyses. Results Ultrasound recordings were performed for the 15 volunteers, unlike electromyography recordings which could be collected in only 9 of 15 patients (60%). Autotriggering was correctly identified by continuous recording of electromyography, excursion, thickening, and flow/pressure tracings with sensitivity of 93% (95% CI, 89–97%), 94% (95% CI, 91–98%), 91% (95% CI, 87–96%), and 79% (95% CI, 75–84%), respectively. Delayed cycling was detected by electromyography, excursion, thickening, and flow/pressure tracings with sensitivity of 84% (95% CI, 77–90%), 86% (95% CI, 80–93%), 89% (95% CI, 83–94%), and 67% (95% CI, 61–73%), respectively. Conclusions Ultrasound is a simple, bedside adjustable, clinical tool to detect the majority of patient–ventilator asynchronies associated with noninvasive ventilation leaks, provided that it is possible to visualize the airway pressure curve on the ultrasound machine screen. Ultrasound detection of autotriggering and delayed cycling is more accurate than isolated observation of pressure and flow tracings, and more feasible than electromyogram. Editor’s Perspective What We Already Know about This Topic Use of noninvasive ventilation in patients with acute respiratory failure is often associated with asynchronies like autotriggering or delayed cycling. These asynchronies are likely to impair efficacy of noninvasive patient ventilation. Surface diaphragm electromyography is the current reference for detecting synchronies in noninvasive ventilation. However this detection technique is not always effective and cannot be used routinely at the bedside. Therefore there is a clinical need for other techniques for monitoring for asynchronies in noninvasive ventilation. What This Article Tells Us That Is New In 15 healthy volunteers, ultrasound assessment of diaphragm excursion and thickening detected noninvasive ventilator asynchronies with high sensitivity and specificity when compared with assessment of respiratory flow/pressure tracings. Surface diaphragm electromyography also had significantly higher sensitivity and specificity for detecting noninvasive ventilator asynchronies, but was only able to be successfully implemented in 60% of the study patients, suggesting that ultrasound assessment of diaphragm excursion and thickening is a more feasible technique for detecting ventilator asynchrony.

Background: Inhalational anesthetic effects on upper airway muscle activity in children are largely unknown. The authors tested the hypothesis that phasic inspiratory genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner in children. Methods: Sixteen children, aged 2.0 to 6.9 yr, scheduled for elective urological surgery were studied. Electromyogram recordings were acquired using intramuscular needle electrodes during spontaneous ventilation. After a 15-min period of equilibration, electromyogram activity was recorded over 30 s at each of three end-tidal concentrations, 1.5, 1.0, and 0.5 minimum alveolar concentration (MAC), administered in sequence. Results: Phasic genioglossus activity was noted in four children at 1.5 MAC, five at 1.0 MAC, and six children at 0.5 MAC sevoflurane. Phasic palatoglossus activity was noted in 4 children at 1.5 MAC, 6 at 1.0 MAC, and 10 children at 0.5 MAC sevoflurane. Both the proportion of children exhibiting phasic activity, and the magnitude of phasic activity increased during recovery from anesthesia. For the genioglossus, decreasing the depth of sevoflurane anesthesia from 1.5 to 1.0 MAC increased phasic activity by approximately 35% and a further decrease to 0.5 MAC more than doubled activity (median [range] at 1.5 and 0.5 MAC: 2.7 μV [0 to 4.0 μV] and 8.6 μV [3.2 to 17.6], respectively; P = 0.029). A similar dose-related increase was recorded at the palatoglossus ( P = 0.0002). Conclusions: Genioglossus and palatoglossus activity increases during recovery from sevoflurane anesthesia in a dose-dependent manner over the clinical range of sevoflurane concentrations in children.

Background The permutation entropy, the approximate entropy, and the index of consciousness are some of the most recently studied electroencephalogram-derived indexes. In this work, a thorough comparison of these indexes was performed using propofol anesthesia in a rabbit model. Methods Six rabbits were anesthetized with three propofol infusion rates: 70, 100, and 130 mg · kg⁻¹ · h⁻¹, each maintained for 30 min, in a random order for each animal. Data recording was performed in the awake animals 20, 25, and 30 min after each infusion rate was begun in the recovered animals and consisted of electroencephalogram recordings, evaluation of depth of anesthesia according to a clinical scale, and arterial blood samples for plasma propofol determination. Median and spectral edge frequencies were analyzed for single-scale permutation entropy and composite multiscale permutation entropy, approximate entropy, index of consciousness, and the spectral parameters. The spectral parameters and single-scale and multiscale permutation entropies were corrected for the presence of burst suppression. Performance of the indexes was compared by prediction probability and pharmacodynamic analysis. Results The single-scale and composite multiscale permutation entropies with a burst suppression correction showed better prediction probabilities than did the other electroencephalogram-derived parameters but not better than the electromyographic activity. Conclusion Single-scale and multiscale permutation entropies may be promising measures of propofol anesthetic depth when corrected for burst suppression. Additional studies should investigate the information measured by electromyography algorithms from commercial monitors of anesthetic depth. The rabbit may be a promising animal model for electroencephalographic studies because it provides a good-quality signal.

Background Anesthetics depress both ventilatory and upper airway dilator muscle activity and thus put the upper airway at risk for collapse. However, these effects are agent-dependent and may involve upper airway and diaphragm muscles to varying degrees. The authors assessed the effects of pentobarbital on upper airway dilator and respiratory pump muscle function in rats and compared these results with the effects of normal sleep. Methods Tracheostomized rats were given increasing doses of pentobarbital to produce deep sedation then light and deep anesthesia, and negative pressure airway stimuli were applied (n = 11). To compare the effects of pentobarbital with those of natural sleep, the authors chronically instrumented rats (n = 10) with genioglossus and neck electromyogram and electroencephalogram electrodes and compared genioglossus activity during wakefulness, sleep (rapid eye movement and non-rapid eye movement), and pentobarbital anesthesia. Results Pentobarbital caused a dose-dependent decrease in ventilation and in phasic diaphragmatic electromyogram by 11 +/- 0.1%, but it increased phasic genioglossus electromyogram by 23 +/- 0.2%. Natural non-rapid eye movement sleep and pentobarbital anesthesia (10 mg/kg intraperitoneally) decreased respiratory genioglossus electromyogram by 61 +/- 29% and 45 +/- 35%, respectively, and natural rapid eye movement sleep caused the greatest decrease in phasic genioglossus electromyogram (95 +/- 0.3%). Conclusions Pentobarbital in rats impairs respiratory genioglossus activity compared to the awake state, but the decrease is no greater than seen during natural sleep. During anesthesia, in the absence of pharyngeal airflow, phasic genioglossus activity is increased in a dose-dependent fashion.

This systematic review describes the evidence on the use of acceleromyography for perioperative neuromuscular monitoring in clinical practice and research. The review documents that although acceleromyography is widely used in research, it cannot be used interchangeably with mechanomyography and electromyography for construction of dose-response curves or for recording different pharmacodynamic variables after injection of a neuromuscular blocking agent. Some studies indicate that it may be beneficial to use a preload to increase the precision of acceleromyography, and to "normalize" the train-of-four ratio to decrease the bias in relation to mechanomyography and electromyography. However, currently the evidence is insufficient to support the routine clinical use of preload and "normalization." In contrast, there is good evidence that acceleromyography improves detection of postoperative residual paralysis. A train-of-four ratio of 1.0 predicts with a high predictive value recovery of pulmonary and upper airway function from neuromuscular blockade.

Background Electromyographic activity has previously been reported to elevate the Bispectral Index (BIS) in patients not receiving neuromuscular blockade while under sedation in the intensive care unit. This study aimed to investigate the magnitude of the decrease of BIS following administration of muscle relaxant in sedated intensive care unit patients. Methods The authors prospectively investigated 45 patients who were continuously sedated with midazolam and sufentanil to achieve a Sedation-Agitation Scale value equal to 1 and who required administration of muscle relaxant. BIS (BIS version 2.10), electromyography, and acceleromyography at the adductor pollicis muscle were recorded simultaneously before and after neuromuscular blockade. Sixteen of these 45 patients were also studied simultaneously with the new BIS XP. Results After administration of a muscle relaxant, BIS (67 +/- 19 vs. 43 +/- 10, P < 0.001) and electromyographic activity (37 +/- 9 vs. 27 +/- 3 dB, P < 0.001) significantly decreased. Multiple regression analysis showed that the decrease of BIS following administration of myorelaxant was significantly correlated to BIS and electromyographic baseline values. Using standard BIS range guidelines, the number of patients under light or deep sedation versus general anesthesia or deep hypnotic state was markedly overestimated before administration of myorelaxant (53 vs. 2%, P < 0.001). Conclusions The BIS in sedated intensive care unit patients may be lower with paralysis for an equivalent degree of sedation because of high muscular activity. The magnitude of BIS overestimation is significantly correlated to both BIS and electromyographic activity before neuromuscular blockade. The authors conclude that clinicians who determine the amount of sedation in intensive care unit patients only from BIS monitoring may expose them to unnecessary oversedation.

Background Reflex abdominal muscle contraction elicited by colorectal distension in male rats is inhibited by mu- and kappa-opioid receptor agonists and sites of action and receptor subtypes have been probed. The authors examined the pharmacology of opioid agonist inhibition in visceral pain related to the uterine cervix, the source of labor pain. Methods Ovariectomized female rats were anesthetized with halothane, and metal rods inserted in the uterine cervix through a small midline laparotomy. After a period of stabilization the cervix was distended by manual separation of the rods, using stimuli of 25-100 g, and reflex rectus abdominis electromyographic activity was recorded. After determining the stimulus response relationship, we tested inhibition of reflex activity by -U50,488 and morphine and their reversal with norbinaltorphimine, or with naltrexone and methyl-naltrexone, respectively. Results Cervical distension produced a stimulus-dependent increase in electromyographic activity, with a threshold of 25 g. Morphine and -U50,488 produced dose-dependent inhibition of the reflex activity. Log linear regression analysis demonstrated an ID50 of 0.03 for morphine, and of 0.05 mg/kg for -U50,488. These effects were reversed by naltrexone, but not by methylnaltrexone or norbinaltorphimine. Conclusions These data suggest that mu- and kappa-opioid receptor agonists effectively inhibit responses to acute uterine cervical stimulation. Lack of reversal by norbinaltorphimine further supports evidence of a novel kappa-opioid receptor by visceral afferents. Lack of morphine reversal by methylnaltrexone suggests central (spinal or supraspinal) sites of action for inhibition of this visceral noxious stimulus.

Background Ketamine is analgesic in experimental and clinical studies of inflammatory, neuropathic, and postoperative pain. Its role in the treatment of visceral pain is less known. The authors investigated the effect and site of action of ketamine on reflex responses evoked by urinary bladder distension (UBD). The effects of other clinically available N-methyl-d-aspartate (NMDA) receptor antagonists on these responses were also studied. Methods The effect of intravenous ketamine (1, 3, and 10 mg/kg), dextromethorphan (5 mg/kg), and memantine (16 mg/kg) on mean arterial pressure changes (Delta MAP) and abdominal electromyographic activity (EMG) evoked by UBD was measured in anesthetized rats. Ketamine was also administered intravesically and intrathecally and its effect on Delta MAP and EMG responses to UBD recorded. The effect of pretreatment with intravenous ketamine on these responses was also assessed. Results The Delta MAP and EMG responses to UBD were reduced in a dose-dependent fashion by ketamine. Memantine and dextromethorphan also inhibited these responses. Ketamine administered intrathecally produced marked inhibition of Delta MAP and EMG responses to UBD. Pretreatment with ketamine only transiently reduced the vigor of responses to UBD. Conclusions Ketamine inhibited, in a dose-dependent fashion, the Delta MAP and EMG responses to UBD, an effect likely caused by actions within the spinal cord. Similar inhibition observed with systemic dextromethorphan and memantine treatments suggests that the analgesic effect of ketamine is caused by antagonism of the NMDA receptor. Pretreatment with ketamine did not have a preventive effect in this model of bladder nociception.

Background During offset of nondepolarizing neuromuscular block, a train-of-four (TOF) fade ratio of 0.70 or greater is considered to reliably indicate the return of single twitch height (T1) to its control value. Studies using mechanomyography or electromyography confirm this observation. The authors' impressions when using the acceleromyograph as a neuromuscular monitor did not support these results. Therefore, the authors studied the relation between T1 and the TOF ratio (when measured by acceleromyography) during recovery from neuromuscular block. Methods Sixteen adult patients were studied. Anesthesia was induced with intravenous opioid plus 2.0-2.5 mg/kg propofol. Laryngeal mask placement or tracheal intubation was accomplished without the use of muscle relaxants. Anesthesia was maintained with nitrous oxide, desflurane (2.0-3.0%, end-tidal), and fentanyl. The response of the thumb to ulnar nerve stimulation was recorded with the TOF-Guard acceleromyograph (Organon Teknika BV, Boxtel, The Netherlands). TOFs were administered every 15 s. After final calibration, 0.15 mg/kg mivacurium was administered. No further relaxants were administered. T1 and the TOF ratio were then recorded until the TOF ratio had returned to its initial value (+/- 5%). Results At a TOF ratio of 0.70 (during recovery of neuromuscular function), T1 averaged only 69 +/- 8% of control. At a TOF ratio of 0.90, T1 averaged 86 +/- 5% of control. To achieve 90% recovery of T1, a TOF ratio of 0.93 +/- 0.08 was required. Conclusion Assumptions regarding the relation between T1 and the TOF ratio derived from studies using mechanomyography and electromyography do not necessarily apply to observations obtained using acceleromyography.

Background Although the uterine cervix is a common source of acute and chronic visceral pain in women, there is practically no neurobiological investigation of nociception from this visceral organ. With use of a novel model of uterine cervical distension nociception in rats, the estrogen dependency of opioid agonist-induced inhibition was investigated. Methods Sprague Dawley rats were anesthetized with halothane and bilateral ovariectomy was performed, after which placebo or estrogen treatment was administered for 1 week. Animals were reanesthetized and fine metal rods were inserted into the uterine cervix for manual distension. Reflex contraction of the rectus abdominis in response to distension was recorded before and after cumulative dosing with the mu-opioid agonist morphine and the kappa-opioid agonist (-)U50488. Results Uterine cervical distension increased reflex abdominal muscle contraction with a threshold of 75 g, regardless of estrogen treatment. Morphine and (-)U50488 reduced the reflex response to cervical distension in a dose-dependent manner. Estrogen reduced the inhibitory effect of morphine but not that of (-)U50488. Conclusions It has been suggested that mu-opioid agonists are less potent in females than males, whereas kappa-opioid agonists are more potent in females than males. These data suggest that estrogen may influence the action of opioids, at least against visceral pain, which may explain this sex difference. In addition, these data suggest that kappa-opioid agonists may be effective in the treatment of pain originating from the uterine cervix, regardless of estrogen status.

Background Respiratory muscles are considered to be more resistant to muscle relaxants as compared with peripheral muscles. However, the relative sensitivity of respiratory muscles participating to the pump function has not been compared. We used electromyography to compare pharmacodynamic parameters of the diaphragm and abdominal muscles after mivacurium. Methods Forty adults undergoing elective surgery were randomly allocated in five dosing groups of mivacurium (50, 100, 150, 200, and 250 microg/kg). Patients anesthetized with propofol and fentanyl underwent intubation without relaxants. Anesthesia was maintained with nitrous oxide and propofol. The right phrenic nerve, the left 10th intercostal nerve, and the ulnar nerve were stimulated. Electromyography of the diaphragm and abdominal muscles was recorded from surface electrodes. Mechanomyography was used to measure adductor pollicis evoked contraction. After a 5-min stable recording period, patients received a single intravenous bolus (20 s) dose of mivacurium. By using log dose-probit effect regression analysis, dose-response curves were constructed. Effective doses and 95% confidence intervals were derived for the diaphragm and abdominal muscles and were compared. Results The dose-response regression line of abdominal muscles differed from that of the diaphragm. Calculated ED50 and ED90 were higher for the diaphragm than for the abdominal muscles (104 [82-127] and 196 [177-213] microg/kg, and 67 [51-82] and 161 [143-181] microg/kg, respectively). The onset of block was faster and recovery of control responses were shorter at the diaphragm than at the abdominal muscles. Conclusion Diaphragm and abdominal muscles have differential sensitivity to mivacurium. The diaphragm is more resistant to mivacurium than abdominal muscles are.

Background A decrease of 1 or 2 degrees C in core temperature may provide protection against cerebral ischemia. However, during corporeal cooling of unanesthetized patients, the initiation of involuntary motor activity (shiver) prevents the reduction of core temperature. The authors' laboratory previously showed that focal facial warming suppressed whole-body shiver. The aim of the current study was to determine whether the use of hand warming alone could suppress shiver in unanesthetized subjects and hence potentiate core cooling. Methods Subjects (n = 8; healthy men) were positioned supine on a circulating water mattress (8-15 degrees C) with a convective-air coverlet (14 degrees C) extending from their necks to their feet. A dynamic protocol was used in which focal hand warming was used to suppress involuntary motor activity, enabling noninvasive cooling to decrease core temperatures. The following parameters were monitored: (1) heart rate; (2) blood pressure; (3) core temperature (rectal, tympanic); (4) cutaneous temperature and heat flux; (5) subjective shiver level (SSL scale 0-10) and thermal comfort index (scale 0-10); (6) metabolic data (n = 6); and (7) electromyograms. Results During cooling without hand warming, involuntary motor activity increased until it was widespread. After subjects reported whole-body shiver (SSL > or = 7), applied hand warming, in all cases, reduced shiver levels (SSL < o r= 3), decreased electromyographic root mean square amplitudes, and allowed core temperature to decrease from 37.0 +/- 0.2 to 35.9 +/- 0.5 degrees C (measured rectally). Conclusions Focal hand warming seems to be valuable in minimizing or eliminating the need to suppress involuntary motor activity pharmacologically when it is desired to induce or maintain mild hypothermia; it may be used in conjunction with facial warming or in cases in which facial warming is contraindicated.

Background Laparoscopic cholecystectomy is presumed to induce a reduction in diaphragmatic activity. Indirect indices of diaphragmatic function based on tidal changes in pressures and cross-section area measurements can be unreliable in the postoperative phase. The present study evaluates diaphragmatic activity by directly recording diaphragmatic EMG (EMGdia) data, along with indirect indices. Methods Thirteen adult patients (American Society of Anesthesiologists physical status I or II) undergoing laparoscopic cholecystectomy were examined preoperatively for inspiratory tidal changes in gastric (Pgas-insp) and esophageal (Peso-insp) pressures, and tidal changes in ribcage (Vthor) and abdominal (Vabd) cross-section areas and then again at 1, 6, and 24 h postoperatively combined with EMGdia recordings. Variations in inspiratory gastric (deltaPgas-insp) and inspiratory transdiaphragmatic (deltaPdi-insp) pressures were derived from the above. Results Laparoscopic cholecystectomy induced a significant reduction in mean deltaPgas-insp, mean deltaPdi-insp, and mean Vabd indicating a reduction of diaphragmatic activity postoperatively. DeltaPdi-insp decreased from 11.8+/-4.0 cm H2O preoperatively to 5.7+/-5.7 cm H2O at 1 h and 6.6+/-5.1 cm H2O at 6 h postoperatively (mean +/- SD; P < 0.05). Vabd decreased from 327.0+/-113.0 ml preoperatively to 174.0+/-65.0 ml at 1 h and 175.0+/-98.0 ml at 6 h postoperatively (mean +/- SD; P < 0.05). These values had partially recovered at 24 h. Conclusion The direct and indirect indices of diaphragmatic activity taken together confirm the presence of reduction in diaphragmatic activity after laparoscopic cholecystectomy followed by its partial recovery at 24 h.

Background Paralysis of the vocal cords is one objective of using relaxants to facilitate tracheal intubation. This study compares the neuromuscular blocking effect of succinylcholine and rocuronium on the larynx, the diaphragm, and the adductor pollicis muscle. Methods Electromyographic response was used to compare the neuromuscular blocking effect of succinylcholine and rocuronium on the laryngeal adductor muscles, the diaphragm, and the adductor pollicis muscle. Sixteen patients undergoing elective surgery were anesthetized with propofol and fentanyl, and their tracheas were intubated without neuromuscular blocking agents. The recurrent laryngeal and phrenic nerves were stimulated at the neck. The electromyographic response was recorded from electrodes placed on the endotracheal tube and intercostally before and after administration of 1 mg/kg succinylcholine or 0.6 mg/kg rocuronium. Results The maximum effect was greater at the adductor pollicis (100 and 99%) than at the larynx (96 and 97%) and the diaphragm (94 and 96%) after administration of succinylcholine and rocuronium, respectively (P < or = 0.05). Onset time was not different between the larynx (58+/-10 s), the diaphragm (57+/-8 s), and the adductor pollicis (54+/-13 s), after succinylcholine (all mean +/- SD). After rocuronium, onset time was 124+/-39 s at the larynx, 130+/-44 s at the diaphragm, and 115+/-21 s at the adductor pollicis. After succinylcholine administration, time to 90% recovery was 8.3+/-3.2, 7.2+/-3.5, and 9.1+/-3.0 min at the larynx, the diaphragm, and the adductor pollicis, respectively. Time to 90% recovery after rocuronium administration was 34.9+/-7.6, 30.4+/-4.2, and 49.1+/-11.4 min at the larynx, the diaphragm, and the adductor pollicis, respectively. Conclusion Neuromuscular blocking effect of muscle relaxants on the larynx can be measured noninvasively by electromyography. Although the larynx appears to be resistant to muscle relaxants, we could not demonstrate that its onset time differed from that of peripheral muscles.

Background Investigators in the authors' laboratory previously established the critical participation of the cerulospinal noradrenergic pathway in muscular rigidity elicited by fentanyl. The identification of colocalization of glutamate with tyrosine hydroxylase in most locus ceruleus neurons suggests a role for cerulospinal glutamatergic neurotransmission in fentanyl-induced muscular rigidity. This suggestion and the subtype(s) of glutamate receptors involved were investigated here. Methods Electromyographic signals activated by bilateral microinjection of 2.5 microg fentanyl into the locus ceruleus were recorded differentially from the left sacrococcygeus dorsi lateralis muscle of adult male Sprague-Dawley rats. The effect of intrathecal administration at the lower lumbar spinal cord of various N-methyl-D-aspartate (NMDA) and non-NMDA receptor antagonists or agonists on this index of muscular rigidity was studied. Rats were under mechanical ventilation, and intravenous infusion of ketamine (30 mg x kg(-1) x h(-1)) was maintained until 10 min before fentanyl was administered. Results Microinjection of fentanyl bilaterally into the locus ceruleus increased the root mean square and decreased the mean power frequency values of electromyographic signals. The efficacy of fentanyl to elicit muscular rigidity in this manner was significantly reduced by previous intrathecal administration of either 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801), D-(-)-2-amino-5-phosphonovaleric acid (AP5), or (+/-)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). Intrathecal administration of kainic acid or NMDA also resulted in significant electromyographic activation. Conclusions In addition to the cerulospinal noradrenergic mechanism, the cerulospinal glutamatergic pathway and both NMDA and non-NMDA receptors in the spinal cord may mediate fentanyl-induced muscular rigidity in the rat.