The Incidence and Mechanisms of Pharyngeal and Upper Esophageal Dysfunction in Partially Paralyzed Humans: Pharyngeal Videoradiography and Simultaneous Manometry after Atracurium

Background: Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection. The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block. The secondary objective was to evaluate the effect of atracurium on pharyngeal function.

Methods: Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy. The initiation of the swallowing process, the pharyngeal coordination, and the bolus transit time were evaluated. Simultaneous manometry was used to document pressure changes at the tongue base, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, an intravenous infusion of atracurium was administered to obtain train-of-four ratios (T4/T1) of 0.60, 0.70, and 0.80, followed by recovery to a train-of-four ratio of more than 0.90.

Results: The incidence of pharyngeal dysfunction was 6% during the control recordings and increased (P < 0.05) to 28%, 17%, and 20% at train-of-four ratios 0.60, 0.70, and 0.80, respectively. After recovery to a train-of-four ratio of more than 0.90, the incidence was 13%. Pharyngeal dysfunction occurred in 74 of 444 swallows, the majority (80%) resulting in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis (P = 0.0081). The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 (P < 0.01). A marked reduction in the upper esophageal sphincter resting tone was found, as well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly.     

The incidence and mechanisms of pharyngeal and upper esophageal dysfunction in partially paralyzed humans: pharyngeal videoradiography and simultaneous manometry after atracurium

BACKGROUND: Residual neuromuscular block caused by vecuronium alters pharyngeal function and impairs airway protection. The primary objectives of this investigation were to radiographically evaluate the swallowing act and to record the incidence of and the mechanism behind pharyngeal dysfunction during partial neuromuscular block. The secondary objective was to evaluate the effect of atracurium on pharyngeal function. METHODS: Twenty healthy volunteers were studied while awake during liquid-contrast bolus swallowing. The incidence of pharyngeal dysfunction was studied by fluoroscopy. The initiation of the swallowing process, the pharyngeal coordination, and the bolus transit time were evaluated. Simultaneous manometry was used to document pressure changes at the tongue base, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, an intravenous infusion of atracurium was administered to obtain train-of-four ratios (T4/T1) of 0.60, 0.70, and 0.80, followed by recovery to a train-of-four ratio of more than 0.90. RESULTS: The incidence of pharyngeal dysfunction was 6% during the control recordings and increased (P < 0.05) to 28%, 17%, and 20% at train-of-four ratios 0.60, 0.70, and 0.80, respectively. After recovery to a train-of-four ratio of more than 0.90, the incidence was 13%. Pharyngeal dysfunction occurred in 74 of 444 swallows, the majority (80%) resulting in laryngeal penetration. The initiation of the swallowing reflex was impaired during partial paralysis (P = 0.0081). The pharyngeal coordination was impaired at train-of-four ratios of 0.60 and 0.70 (P < 0.01). A marked reduction in the upper esophageal sphincter resting tone was found, as well as a reduced contraction force in the pharyngeal constrictor muscles. The bolus transit time did not change significantly. CONCLUSION: Partial neuromuscular paralysis caused by atracurium is associated with a four- to fivefold increase in the incidence of misdirected swallowing. The mechanism behind the pharyngeal dysfunction is a delayed initiation of the swallowing reflex, impaired pharyngeal muscle function, and impaired coordination. The majority of misdirected swallows resulted in penetration of bolus to the larynx.     

Pharyngeal Function and Airway Protection During Subhypnotic Concentrations of Propofol, Isoflurane, and Sevoflurane: Volunteers Examined by Pharyngeal Videoradiography and Simultaneous Manometry

Background : Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect.

Methods : Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50asleep) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)awake for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery.

Results : All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50asleep had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 +/- 36 to 39 +/- 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 +/- 16 to 45 +/- 18 mmHg at 0.50 MACawake (P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002).     

Pharyngeal function and airway protection during subhypnotic concentrations of propofol, isoflurane, and sevoflurane: volunteers examined by pharyngeal videoradiography and simultaneous manometry.

BACKGROUND: Anesthetic agents alter pharyngeal function with risk of impaired airway protection and aspiration. This study was performed to evaluate pharyngeal function during subhypnotic concentrations of propofol, isoflurane, and sevoflurane and to compare the drugs for possible differences in this respect. METHODS: Forty-five healthy volunteers were randomized to receive propofol, isoflurane, or sevoflurane. During series of liquid contrast bolus swallowing, fluoroscopy and simultaneous solid state videomanometry was used to study the incidence of pharyngeal dysfunction, the initiation of swallowing, and the bolus transit time. Pressure changes were recorded at the back of the tongue, the pharyngeal constrictor muscles, and the upper esophageal sphincter. After control recordings, the anesthetic was delivered, and measurements were made at 0.50 and 0.25 predicted blood propotol concentration (Cp50(asleep)) for propofol and 0.50 and 0.25 minimum alveolar concentration (MAC)(awake) for the inhalational agents. Final recordings were made 20 min after the end of anesthetic delivery. RESULTS: All anesthetics caused an increased incidence of pharyngeal dysfunction with laryngeal bolus penetration. Propofol increased the incidence from 8 to 58%, isoflurane from 4 to 36%, and sevoflurane from 6 to 35%. Propofol in 0.50 and 0.25 Cp50(asleep) had the most extensive effect on the pharyngeal contraction patterns (P < 0.05). The upper esophageal sphincter resting tone was markedly reduced from 83 +/- 36 to 39 +/- 19 mmHg by propofol (P < 0.001), which differed from isoflurane (P = 0.03). Sevoflurane also reduced the upper esophageal sphincter resting tone from 65 +/- 16 to 45 +/- 18 mmHg at 0.50 MAC(awake)(P = 0.008). All agents caused a reduced upper esophageal sphincter peak contraction amplitude (P < 0.05), and the reduction was greatest in the propofol group (P = 0.002). CONCLUSION: Subhypnotic concentrations of propofol, isoflurane, and sevoflurane cause an increased incidence of pharyngeal dysfunction with penetration of bolus to the larynx. The effect on the pharyngeal contraction pattern was most pronounced in the propofol group, with markedly reduced contraction forces.     

Ventilation and neuromuscular blocking drugs

Ventilatory failure after administration of neuromuscular blocking agents is an important factor in anaesthesia-related perioperative morbidity and mortality. Improved knowledge and new monitoring methods may avoid ventilatory failure caused by incomplete recovery of neuromuscular function in the postoperative period. Central respiratory muscles are less sensitive than, and their time course of neuromuscular block is different from those of, pharyngeal muscles and those of the upper airway. Differences in potency and time course of neuromuscular block may lead to incorrect assessment of ventilatory function during onset and recovery. Even if recovery of the mechanical adductor pollicis train-of-four (TOF) response to a ratio of 0.70 has previously been associated with adequate ventilatory capacity, it is now shown that hypoxic ventilatory responses may be markedly reduced despite adequate respiratory force at a TOF ratio of 0.70. Hence, partial paralysis may interfere with ventilatory regulation in hypoxaemia. Consequently, monitoring neuromuscular function by peripheral nerve stimulation in one muscle yields limited information about total ventilatory capacity, especially the function of the upper airway and ventilatory regulation. Therefore, neuromuscular monitoring should be used with caution during recovery and should always be combined with bedside clinical tests if possible.     

The effect of bolus consistency on dysphagia in unilateral vocal cord paralysis

OBJECTIVE: To examine the risk of aspiration for liquid versus paste bolus consistencies in patients with unilateral vocal cord paralysis (UVCP). METHODS: The swallowing function of adult patients with UVCP was prospectively studied videofluorographically to examine the incidence of laryngeal penetration and aspiration for both liquid and paste boluses. The degree of penetration or aspiration was quantified using the penetration-aspiration scale (PAS). The presence and location of pharyngeal bolus residue were also documented for each consistency. Results were compared between liquid and paste bolus consistencies. RESULTS: Fifty-five patients with UVCP were studied with a mean age of 60.2 years. Intrathoracic surgery or malignancy accounted for 38 (69.1%) of cases. The mean PAS scores for liquid and paste bolus consistency were 3.1 vs. 1.5, respectively (P < 0.001). The liquid bolus penetrated in 19 (34.5%) patients and was aspirated in 11 (20%) patients. In contrast, the paste bolus penetrated in 12 (21.8%) cases and was aspirated in 0 cases (P < 0.001). Pharyngeal residue was more likely to occur at the base of the tongue or vallecula for the paste bolus consistency versus the liquid bolus. CONCLUSIONS: A significant percentage of patients with UVCP will aspirate thin liquids. Paste bolus consistencies are safer for patients with UVCP as they are much less likely to lead to penetration or aspiration despite a higher prevalence of pharyngeal residue.     

Acetylcholine receptor density in human cricopharyngeal muscle and pharyngeal constrictor muscle

BACKGROUND: Upper esophageal sphincter resting tone is reduced during partial neuromuscular block, whereas contraction of the pharyngeal constrictor muscle is only slightly affected. We hypothesized that this difference may arise from differential nicotinic acetylcholine receptor (nAChR) density, the density supposedly being lower in the more sensitive cricopharyngeal muscle than in the resistant pharyngeal constrictor muscle. The aim of this study was to determine the density of nAChR in the main component of the upper esophageal sphincter, the cricopharyngeal muscle, and in the pharyngeal constrictor muscle. METHOD: After approval by the institutional ethics committee and informed consent, muscle specimens were obtained from five patients undergoing surgery with laryngectomy for malignancies of the larynx or thyroid gland. None had received radiation therapy to the affected area. The nAChR from these tissue specimens were solubilized and incubated with 125I-alpha-bungarotoxin. The quantity of radioligand-receptor complex was measured by radioactive decay in a liquid scintillation counter. The receptor density was expressed as femtomoles per milligram of protein (fmol/mg protein). RESULTS: The nAChR density was determined to 6.8 (3.5) fmol/mg protein (mean (SD)) in the cricopharyngeal muscle and 5.6 (2.1) fmol/mg protein in the pharyngeal constrictor muscle (P = 0.22). Although we could not find any difference in mean nAChR density, contrary to our hypothesis, the density in four of the five patients was higher in the cricopharyngeal muscle than in the pharyngeal constrictor muscle. CONCLUSION: Our results indicate that the density of nicotinic acetylcholine receptors is similar in the cricopharyngeal muscle and in the pharyngeal constrictor muscle. Nicotinic acetylcholine receptor density, as determined by 125I-alpha-bungarotoxin assay, cannot explain the difference in response to neuromuscular blocking drugs between the investigated muscles.     

Fiber-type composition and fiber size of the human cricopharyngeal muscle and the pharyngeal constrictor muscle

Background:  Despite a similar density of nicotinic acetylcholine receptors, the upper esophageal sphincter is sensitive to partial neuromuscular block, whereas the pharyngeal constrictor muscle is more resistant. In order to postulate possible mechanisms behind this difference in pharmacological response, basic knowledge of morphological and physiological features of these muscles is needed. The aim of this study was to compare the muscle fiber-type composition, the size and the morphology of the muscle fibers of the cricopharyngeal muscle, the main component of the upper esophageal sphincter, with that of the pharyngeal constrictor muscle.
Methods:  Muscle specimens were obtained from five patients undergoing surgery with laryngectomy. Muscle fiber type was determined by myosin heavy chain immunohistochemistry and the muscle fiber cross-sectional area was measured for each fiber type by planimetry. Morphology of muscle fibers was evaluated by histochemistry.
Results:  The muscle fiber cross-sectional area was generally smaller in the cricopharyngeal muscle compared with the pharyngeal constrictor muscle ( P <  0.001). The composition of fiber types showed a large interindividual variability with no distinct difference between the studied muscles. Aberrant histological features were common in both the cricopharyngeal muscle and the pharyngeal constrictor muscle.
Conclusion:  The main morphological difference between the neuromuscular blocking agents sensitive cricopharyngeal muscle and the more resistant pharyngeal constrictor muscle is a uniformly smaller size of contributing fiber types in the cricopharyngeal muscle than in the pharyngeal constrictor muscle. The muscle fiber-type composition does not differ between the two studied muscles.     

Relationship of the Train-of-four Fade Ratio to Clinical Signs and Symptoms of Residual Paralysis in Awake Volunteers

Background: Recovery of the train-of-four (TOF) ratio to a value > 0.70 is synonymous with adequate return of neuromuscular function, but there is little information available concerning the subjective experience that accompanies residual neuromuscular block wherein the TOF ratio is in the range of 0.70 to 0.90.

Methods: Ten American Society of Anesthesiologists' (ASA) physical status 1 volunteers were studied. Control measurements included grip strength in kilograms and ability to perform a 5-s head- and leg-lift. In addition, a standard wooden tongue depressor was placed between each subject's incisor teeth, and he or she was told not to let the investigator remove it. All subjects were easily able to retain the device despite vigorous attempts to dislodge it. Neuromuscular function was monitored with a Datex(TM) (Datex Medical Instrumentation, Inc., Tewksbury, MA) 221 electromyographic (EMG) monitor. TOF stimulation was given every 20 s, and the measured TOF fade ratio was continuously recorded. A 5 mg/kg bolus of mivacurium was then administered, and an infusion at 2 mg [center dot] kg sup -1 [center dot] min sup -1 was begun. The infusion was continued until the TOF ratio decreased to < 0.70 and was adjusted to keep it in the range of 0.65 to 0.75. Signs and symptoms of weakness were recorded when the TOF ratio had been stable +/- 0.03 for at least 10 min during an interval when there were no adjustments in the infusion. All tests noted previously were repeated at this time. The TOF ratio was then allowed to recover to 0.85-0.90. When stable at this level, all tests were repeated, and the infusion was discontinued. TOF measurements were continued until a ratio of 1.0 was attained and until a final set of observations was recorded.

Results: The TOF ratio in all subjects was reduced to < 0.70. No volunteers required intervention to maintain a patent airway, and the hemoglobin oxygen saturation while breathing air was greater or equal to 96% at all times. TOF ratios less or equal to 0.90 were accompanied by diplopia and difficulty in tracking moving objects in all subjects. The ability to strongly appose the incisor teeth did not return until the TOF ratio (on average) exceeded 0.85. A sustained 5-s head-lift was not achieved until the TOF ratio averaged 0.60 (range, 0.45-0.75). At a TOF ratio of 0.70, grip strength averaged 59% of control (range, 50-75%). With certain exceptions (vision, ability to clench the teeth tightly), there was wide variation in symptomatology between patients for any given TOF ratio. It is impossible to give reliable TOF break-points at which symptoms and signs will be present or absent.     

Evaluation of residual neuromuscular blockade using modified double burst stimulation

Background: To assess the degree of residual neuromuscular blockade, double burst stimulation (DBS) is commonly applied in the clinical setting. However, fades in response to DBS_3,3 can rarely be identified manually when train-of-four (TOF) ratios are ≧0.70, and, in contrast, fades in response to DBS_3,2 are felt manually in an undesirably high proportion of cases, even at TOF ratios greater than 0.7. We investigated whether a new monitoring method, modified DBS, would be useful to determine an adequate degree of recovery from neuromuscular blockade. For modified DBS, two burst stimuli were applied at an interval of 750 ms. The first stimulation in the modified DBS consisted of two stimuli of 0.3 ms duration at 50 Hz and the second of two stimuli of 0.2 ms duration at 50 Hz. Methods: Forty-five adult patients undergoing elective nitrous oxide-oxygen-isoflurane anesthesia were randomly divided into one of three groups: DBS_3,3 group (n=15), DBS_3,2 group (n=15), or modified DBS group (n=15). During recovery from vecuroni-um-induced neuromuscular blockade, on both forearms, DBS_{3, 3}, DBS_{3, 2}, and modified DBS were delivered in the DBS_{3, 3} group, DBS_{3, 2} group, and modified DBS group, respectively. One hand and forearm (fixed arm) were immobilized to quantify the degree of neuromuscular blockade mechanically, and the contralateral arm (free arm) was unrestrained. An observer deter-mined tactilely on the free arm the presence or absence of fade in response to the three DBS patterns. Results: Probabilities of detection of fade in response to the DBS_{3, 3} were 67% (TOF ratio of 0.51–0.60), 40% (0.61–0.70), 19% (0.71–4).80), 5% (0.81–0.90), and 0% (0.91–1.00). Those to the DBS₃, ₂ were 95% (0.51–0.60), 93% (0.61–0.70), 83% (0.71–0.80), 65% (0.81–0.90), and 38% (0.91–1.00). Those to modified DBS were 90% (0.51–0.60), 86% (0.61–0.70), 65% (0.71–0.80), 25% (0.81–0.90), and 3% (0.91–1.00). The modified DBS was more sensitive in diagnosing residual neuromuscular blockade than DBS_{3, 3} at the TOF ratio of 0.51–0.90, but was less sensitive than DBS_{3, 2} at the TOF ratio of 0.81–1.00 (P < 0.05). Conclusion: Our results indicate that the modified DBS may be a useful stimulation pattern to diagnose the adequacy of recovery from neuromuscular blockade.     

Double burst stimulation2,3: a new stimulating pattern for residual neuromuscular block

Purpose

We present a new stimulating pattern: double burst stimulation_2,3 (DBS_2,3) for evaluating residual neuromuscular block.

Methods

Forty adult patients were studied. For DBS_2,3, two burst stimuli were applied every 750 msec. The first consisted of two tetanic stimuli of 0.2 msec duration and the second of three tetanic stimuli of 0.2 msec duration. At varying degrees of neuromuscular block induced by vecuronium, the presence or absence of fade, or the presence or absence of waxing (i.e., the feeling that the muscular contraction in response to the second burst was stronger than that to the first) was determined by an observer blinded to the depth of neuromuscular block. In addition, the relationship between the train-of-four (TOF) ratio and DBS_2,3 ratio was established at varying depths of neuromuscular block (TOF ratio 0.04–1.00).

Results

The probabilities of tactile detection of fade in response to DBS_2,3 were 100, 76, 15, 9, 3, 0, and 0% at a TOF ratio of 0–0.40, 0.41–0.50, 0.51–0.60, 0.61–0.70, 0.71–0.80, 0.81–0.90, and 0.91–1.00, respectively. Waxing in response to the DBS_2,3 was identified in 0, 6, 32, 84, and 98% of cases when the TOF ratios were 0.00–0.60, 0.61–0.70, 0.71–0.80, 0.81–0.90, and 0.91–1.00, respectively. A close linear relationship existed between the TOF ratio and DBS_2,3 ratio (r = 0.96, P < 0.000001).

Conclusion

DBS_2,3 is of clinical use because when residual neuromuscular block is clinically important, fade can be identified, but once neuromuscular function returns to a sufficient level, waxing can be detected.     

Attenuated ventilatory response to hypoxaemia at vecuronium-induced partial neuromuscular block

The effect of a partial neuromuscular block on the ventilatory response to hypercarbia and to hypoxaemia was studied in 11 non-anaesthetized male subjects. Respiratory frequency, tidal volume, minute volume, respiratory timing and drive were measured during air breathing and during stimulation by hypercarbia and hypoxaemia. The ventilatory response was defined as the ratio between, respectively, tidal volume and minute volume during ventilation stimulated by hypercarbia and hypoxaemia compared to measurements during air breathing. The ventilatory measurements were repeated on three separate occasions: before neuromuscular block was established, during an infusion of vecuronium aiming at a mechanical adductor pollicis train-of-four (TOF) ratio of 0.70, and after the infusion had been stopped and the neuromuscular block had spontaneously recovered to a TOF ratio of > 0.90. Resting ventilation during air breathing remained with minor variations throughout the experiment. The ventilatory response to hypercarbia was not affected at a TOF ratio of 0.70 as compared to measurements before vecuronium and at a TOF ratio of > 0.90. In contrast, the ventilatory response to hypoxaemia was markedly reduced at a TOF ratio of 0.70. We conclude that a mechanical TOF ratio of 0.70 following vecuronium may be associated with an inadequate ventilatory response to hypoxaemia.     

Gastric reflux and pulmonary aspiration in anaesthesia

Although aspiration is a relatively rare event during anaesthesia, it represent an important cause of anaesthesia related mortality and also of ventilator associated pneumonia in intensive care unit. The incidence of aspiration is markedly increased after trauma owing to the risk of recent ingestion of food, depression of consciousness and airways reflexes, and gastric stasis induced by raised sympathoadrenal tone. The factors which contribute to the likelihood of aspiration include the urgency of surgery, airways problems, inadequate depth of anaesthetic, use of the lithotomy position, gastrointestinal problems, depressed consciousness, increased severity of illness and obesity. Factors that predispose to aspiration pneumonia are: a gastric content with a pH less than 2.5 and a gastric volume of 0.4 ml kg-1; a reduction in lower oesophageal sphincter tone; a reduction of upper oesophageal sphincter tone and a not coordination between the pharyngeal muscle and the upper oesophageal sphincter tone during swallowing; and a depression of protective airway reflexes. Methods to minimize regurgitation and aspiration involve control of gastric contents (preoperative starvation is the method universal accepted), application of cricoid pressure and control of the airways.     

Antagonism of profound cisatracurium and rocuronium block: the role of objective assessment of neuromuscular function

STUDY OBJECTIVE: The purpose of this study is to determine the incidence of significant (train-of-four [TOF] ratio <0.70), but clinically undetectable (TOF ratio >0.40), residual neuromuscular block after neostigmine antagonism of profound cisatracurium (CIS) or rocuronium (ROC) block. DESIGN: Prospective, randomized, open-label study. SETTING: University hospital. PATIENTS: Forty ASA physical status I and II undergoing elective surgical procedures. INTERVENTIONS: Anesthesia was induced with propofol 1.5 to 2.5 mg/kg IV plus fentanyl 2 to 4 mug/kg and maintained with N(2)O/desflurane plus narcotic supplementation. The electromyographic response of the adductor pollicis was recorded. Train-of-four stimulation was given every 20 seconds. Twitch height (T1) and TOF fade ratio were continuously recorded. In group 1 (n = 20), neuromuscular block was induced with CIS 0.10 mg/kg, and T1 was maintained at 5% of control by a constant infusion of CIS until the end of surgery. One minute after the termination of the infusion, neostigmine 0.05 mg/kg was administered. T1 and TOF values were monitored continuously for the next 20 minutes. Group 2 (n = 20) is identical to group 1 except that the initial drug was ROC 0.60 mg/kg, and paralysis was maintained with an infusion of ROC. MEASUREMENTS AND MAIN RESULTS: There were no significant differences in the recovery patterns of CIS vs ROC. The duration (bolus to end of infusion) in both groups averaged 2.7 hours, and the mean cumulative dose of relaxant approximated 4 x the ED(95). T1 at the time of reversal was 6% (4%-10%) of control. Mean TOF ratios at 10, 15, and 20 minutes were 0.55, 0.71, and 0.0.81, respectively. Return to a TOF ratio >0.40 was always achieved in 15 minutes or less. However, at 20 minutes postreversal, 5 of 40 subjects had TOF ratios <0.70 and only 11 individuals had recovered to a TOF ratio of 0.90 or greater. CONCLUSIONS: Most clinicians cannot detect tactile fade once the TOF ratio exceeds 0.40. When reversing profound block, an objective monitor of neuromuscular function is required if the extent of residual block is to be assessed with any confidence.     

Antagonism of cisatracurium and rocuronium block at a tactile train-of-four count of 2: should quantitative assessment of neuromuscular function be mandatory?

With a train-of-four (TOF) ratio >0.70 as the standard of acceptable recovery, postoperative residual paralysis is a frequent occurrence in postanesthesia care units (PACUs). However, detailed information regarding prior anesthetic management is rarely provided. We examined the incidence of postoperative weakness after the administration of cisatracurium and rocuronium when using a rigid protocol for muscle relaxant and subsequent neostigmine administration. Under desflurane, N(2)O, and opioid anesthesia, tracheal intubation was accomplished after either cisatracurium 0.15 mg/kg or rocuronium 0.60 mg/kg. The response of the thumb to ulnar nerve stimulation was estimated by palpation. Additional increments of muscle relaxant were given as needed to maintain the TOF count at 1 or 2. At the conclusion of surgery, at a TOF count of 2, neostigmine 0.05 mg/kg plus glycopyrrolate 10 micro g/kg was administered. The mechanical TOF response was then measured with a force transducer starting 5 min postreversal. Patients were observed until a TOF ratio of 0.90 was achieved. There were no significant differences in the recovery profiles of cisatracurium versus rocuronium. TOF ratios at 10 min postreversal were 0.72 +/- 0.10 and 0.76 +/- 0.11, respectively. At 15 min postreversal, only one subject in each group had a TOF ratio of <0.70. No patient in either group arrived in the PACU with a TOF ratio <0.70. Our results suggest that if cisatracurium or rocuronium is administered by using the TOF count as a guide, critical episodes of postoperative weakness in the PACU should be an infrequent occurrence. IMPLICATIONS: After the administration of cisatracurium or rocuronium, train-of-four (TOF) ratios <0.70 should rarely be observed in the postanesthesia care unit if neostigmine-assisted antagonism of residual block is delayed until the tactile TOF count at the thumb is 2 or more.     

Accelerometry of adductor pollicis muscle predicts recovery of respiratory function from neuromuscular blockade

BACKGROUND: Residual paralysis increases the risk of pulmonary complications but is difficult to detect. To test the hypothesis that accelerometry predicts effects of residual paralysis on pulmonary and upper airway function, the authors related tests of pulmonary and pharyngeal function to accelerometry of adductor pollicis muscle in 12 partially paralyzed volunteers. METHODS: Rocuronium (0.01 mg/kg + 2-10 microg x kg-1 x min-1) was administered to maintain train-of-four (TOF) ratios (assessed every 15 s) of approximately 0.5 and 0.8 over a period of more than 5 min. The authors evaluated pharyngeal and facial muscle functions during steady state relaxation and performed spirometric measurements every 5 min until recovery. Upper airway obstruction was defined as a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of greater than 1. The TOF ratio associated with "acceptable" pulmonary recovery (forced vital capacity and forced inspiratory volume in 1 s of > or =90% of baseline) was calculated using a linear regression model. RESULTS: At peak blockade (TOF ratio 0.5 +/- 0.16), forced inspiratory flow was impaired (53 +/- 19%) to a greater degree than forced expiratory flow (75 +/- 20%) with a mean ratio of expiratory and inspiratory flow at 50% of vital capacity of 1.18 +/- 0.6. Upper airway obstruction, observed in 8 of 12 volunteers, paralleled an impaired ability to swallow reported by 10 of 12 volunteers. In contrast, all volunteers except one could sustain a head lift for more than 5 s. The authors calculated that a mean TOF ratio of 0.56 (95% confidence interval, 0.22-0.71) predicts "acceptable" recovery of forced vital capacity, whereas forced inspiratory volume in 1 s was impaired until a TOF ratio of 0.95 (0.82-1.18) was reached. A 100% recovery of TOF ratio predicts an acceptable recovery of forced vital capacity, forced inspiratory volume in 1 s, and mean ratio of expiratory and inspiratory flow at 50% of vital capacity in 93%, 73%, and 88% of measurements (calculated negative predictive values), respectively. CONCLUSION: Impaired inspiratory flow and upper airway obstruction frequently occur during minimal neuromuscular blockade (TOF ratio 0.8), and extubation may put the patient at risk. Although a TOF ratio of unity predicts a high probability of adequate recovery from neuromuscular blockade, respiratory function can still be impaired.     

Reduced hypoxic chemosensitivity in partially paralysed man. A new property of muscle relaxants?

Background: It was hypothesized that non-depolarizing neuromuscular blocking agents impair hypoxic chemosensitivity in man.
Methods: In thirty randomly allocated male volunteers the hypoxic and hypercarbic ventilatory responses were measured during partial paralysis (TOF ratio 0.70) due to either atracurium (n=10), pancuronium (n=10) or vecuronium (n=10).
Results: Hypoxic ventilatory responses were depressed by 306, 287 and 296% (mean SD) at steady-state infusion of atracurium, pancuronium and vecuronium, respectively. At a TOF ratio of >0.90, the HVR was not different from control measurements.
Conclusion: It is concluded that non-depolarizing neuromuscular blocking agents impair hypoxic ventilatory regulation. Further experimental studies are warranted to fully describe the mechanism(s) responsible for this interaction.     

Residual neuromuscular blockade: incidence, assessment, and relevance in the postoperative period

The residual effects of neuromuscular blocking agents may persist into the early postoperative recovery period, even when neuromuscular blockade is carefully monitored and reversed in the operating room. Recent data suggest that mild degrees of residual paresis (train-of-four TOF ratios of 0.7-0.9) may be associated with significant impairment of respiratory and pharyngeal muscle function. Therefore, the new gold standard reflecting acceptable neuromuscular recovery is a TOF ratio > or =0.9. Several investigations have demonstrated that many patients continue to arrive in the postanesthesia care unit with TOF ratios <0.7-0.9. Several techniques may be used to reduce the risk of postoperative residual paresis, which include avoidance of long-acting muscle relaxants, use of neuromuscular monitoring in the operating room, routine reversal of neuromuscular blockade at a TOF count of 2-3, and early administration of reversal agents. Careful management of neuromuscular blockade may limit the occurrence of adverse events associated with residual postoperative paralysis. Large-scale outcome studies are needed to clearly define the impact of residual neuromuscular block on major morbidity and mortality in surgical patients.     

The Relationship between Acceleromyographic Train-of-four Fade and Single Twitch Depression

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(R) 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.     

Priming principle with atracurium

In order to substantiate the "priming principle" discussion, 44 patients admitted for elective gynecological surgery under modified neurolept anesthesia were randomized into two groups. In group I, atracurium was administered by a priming technique in which 0.1 mg/kg was given i.v. and, after 6 min, 0.5 mg/kg. In group II was given an atracurium bolus injection of 0.6 mg/kg. In group I onset time (median 61 sec, range 44-160 sec) was significantly more rapid than in group II (median 83 sec, range 60-128 sec). The median train-of-four ratio in group I was 0.80 (range 0.43-1.00, n = 23), 6 min after the priming dose, in 30% of these patients the TOF ratio was above 0.90 and in 22% below 0.70. It is impossible to determine a fixed pretreatment dose per kg body weight owing to the large individual variation in neuromuscular depression. Modification of the priming principle using incremental small doses of non-depolarizing neuromuscular blocking agents, with anesthetic induction, when the train-of-four ratio is between 0.90 and 0.70 or when there is clinical signs of neuromuscular block, might be an alternative in situations where rapid induction is required and where the use of suxamethonium is contraindicated.