Modulation of Cerebral Function by Muscle Afferent Activity, with Reference to Intravenous Succinylcholine.

Cerebral Function and Muscle Afferent Activity Following Intravenous Succinylcholine in Dogs Anesthetized with Halothane: The Effects of Pretreatment with a Defasciculating Dose of Pancuronium. By WL Lanier, PA Iaizzo, and JH Milde. Anesthesiology 1989; 71:87-95. Reprinted with permission. By the mid-1980s, it was widely assumed that if the depolarizing muscle relaxant, succinylcholine, given IV, produced increases in intracranial pressure, it did so because fasciculations produced increases in intrathoracic and central venous pressures that were transferred to the brain; however, there was no direct evidence that this was true. In contrast, we explored the possibility that the succinylcholine effect on the brain was explained by the afferentation theory of cerebral arousal, which predicts that agents or maneuvers that stimulate muscle stretch receptors will tend to stimulate the brain. Our research in tracheally intubated, lightly anesthetized dogs discovered that IV succinylcholine (which does not cross the blood-brain barrier) produced a doubling of cerebral blood flow that lasted for 30 min and corresponded to activation of the electroencephalogram and increases in intracranial pressure. Later, in our Classic Paper, we were able to assess simultaneously cerebral physiology and afferent nerve traffic emanating from muscle stretch receptors (primarily muscle spindles). We affirmed that the cerebral arousal response to succinylcholine was indeed driven by muscle afferent traffic and was independent of fasciculations or increases in intrathoracic or central venous pressures. Later research in complementary models demonstrated that endogenous movement (e.g., coughing, hiccups) produced a cerebral response very similar to IV succinylcholine, apparently as a result of the same muscle afferent mechanisms, independent of intrathoracic and central venous pressures. Thus, the importance of afferentation theory as a driver of the cerebral state of arousal and cerebral physiology during anesthesia was affirmed.

Ultrasound-Guided Botulinum Toxin Injection for the Treatment of Teres Major Fasciculations.

ABSTRACT: This case study presents a 31-yr-old male weightlifter without known neuromuscular disease who presented with 5 wks of atraumatic, constant fasciculations of his right teres major muscle without recent injury. Electromyography identified fasciculation potentials within the teres major and pronator teres, suggesting an acute C6 radiculopathy, although a cervical magnetic resonance imaging demonstrated no significant neuroforaminal stenosis. Trigger point injections and multiple medications failed to stop the fasciculations. Under electromyography and ultrasound guidance, he was focally injected with botulinum toxin to the teres major 10 wks from initial onset with subsequent complete resolution of the symptoms and no side effects.

[Case of anti VGKC-complex antibody associated disorder presenting with severe pain and fasciculations predominant in unilateral upper extremity].

A 21-year-old man complained of severe pain and muscle twitching localized in his right arm. Neurological examination showed muscle fasciculations in his right forearm but no myokymia or myotonia. Needle electromyography revealed fibrillation potentials in his biceps brachii muscle and extensor carpi radialis muscle at rest but no myokymic discharges. His serum anti-voltage-gated potassium channel (VGKC)-complex antibody level was significantly high (194.2pM; controls <100pM). Although anticonvulsant therapy relieved his pain, he was readmitted to our hospital because of severe pain in his left arm and both thighs three months later. A high-dose intravenous immunoglobulin (IVIG) therapy followed by steroid pulse therapy relieved his pain. This case with neither muscle cramp nor myokymia expands the phenotype of anti VGKC-complex antibody associated disorder.

Defining normal duration for afterdischarges with repetitive nerve stimulation: a pilot study.

The presence of afterdischarges on repetitive nerve stimulation may be useful to diagnose cramp fasciculation syndrome, however, the presence and normal duration of afterdischarges has not been well-defined in the normal population and individuals with other neuromuscular diseases. The aim of this pilot study was to describe the distribution of afterdischarge durations in normal controls and patients with peripheral neuropathy. The estimated seventy-fifth percentiles of the afterdischarge durations following tibial nerve repetitive nerve stimulation at 2, 5, 10, and 20 Hz were 315, 688, 745, and 928 milliseconds for 18 normal patients, and 143, 31, 323, and 542 milliseconds for 18 peripheral neuropathy patients respectively. Afterdischarge durations were similar in peripheral neuropathy patients and controls. These findings suggest that afterdischarge durations of more than 500 milliseconds are common in normal controls without subjective cramps and patients with peripheral neuropathy, with some durations beyond 1,000 milliseconds. Therefore, the presence of afterdischarges on repetitive nerve stimulation should be interpreted with caution when evaluating patients for hyperexcitable nerve syndromes.

Topographical mapping and mechanical pain sensitivity of myofascial trigger points in the infraspinatus muscle.

OBJECTIVES: To screen for the presence of latent and active myofascial trigger points (MTrPs) in patients with unilateral shoulder and arm pain and perform topographical mapping of mechanical pain sensitivity bilaterally in the infraspinatus muscles. METHODS: Nineteen patients with unilateral musculoskeletal shoulder pain participated in the study. The area overlying the infraspinatus on each side was divided into 10 adjacent sub-areas of 1cm(2), corresponding to the area of a pressure algometer probe. Pressure pain threshold (PPT) was measured in each sub-area bilaterally in the infraspinatus muscles. Following PPT measurement, an acupuncture needle was inserted into each sub-area five times in different directions in order to induce local twitch response and/or referred pain. RESULTS: A significantly lower PPT level in the infraspinatus muscle was detected on the painful side compared with the non-painful side (P=0.001). PPT at midfiber region of the infraspinatus muscles was lower than that at other muscle parts (P<0.05). Multiple, but not single, active MTrPs were found in the infraspinatus muscle on the painful side and there were also multiple latent MTrPs bilaterally in the infraspinatus muscles. PPT at active MTrPs was much lower than the latent MTrPs and again lower than the non-MTrPs. CONCLUSIONS: There exists bilateral mechanical hyperalgesia in patients with unilateral shoulder pain. Further, the association of multiple active MTrPs with unilateral shoulder pain and the heterogeneity of mechanical pain sensitivity distribution suggest a crucial role of peripheral sensitization in chronic myofascial pain conditions. Additionally, the locations of MTrPs identified with dry needling correspond well to PPT topographical mapping, suggesting that dry needling and PPT topographical mapping are sensitive techniques in the identification of MTrPs.

Selective stimulation of the canine hypoglossal nerve using a multi-contact cuff electrode.

Electrical activation of the tongue protrusor muscle has been demonstrated as an effective technique for alleviating upper airway (UAW) obstructions and is considered a potential treatment for obstructive sleep apnea (OSA). Recent studies, however, have shown marked improvements in UAW patency by coactivating the tongue protrudor and retractor muscles. As such, selective stimulation of the hypoglossal nerve (XII) using a single implantable device presents an attractive approach for treating OSA. In order to demonstrate the feasibility of such a device, the maximum achievable stimulation selectivity of the Flat Interface Nerve Electrode (FINE) was investigated. The XII nerve of beagles was stimulated with an acutely implanted FINE, while the corresponding neural and muscular responses were recorded and analyzed. The overall performance of the FINE, as depicted by the average of the maximum target-specific selectivity values, S(i), confirmed that high degrees of selectivity can be achieved at both the fascicular and muscular levels: 0.93 +/- 0.03 (n = 5) and 0.88 +/- 0.03 (n = 4), respectively. The results of this study demonstrate the feasibility of the FINE for selective stimulation of the XII nerve branches and the innervated tongue muscles.

Effects of high-dose propofol on succinylcholine-induced fasciculations and myalgia.

BACKGROUND: The purpose of this prospective study was to determine the effects of high-dose propofol on the incidence of fasciculations and myalgia, and to evaluate changes in creatine kinase levels following the administration of succinylcholine in 90 women who underwent laparoscopy. METHODS: Patients were randomly assigned to one of three groups. Induction of anesthesia was performed with thiopentone 5 mg kg(-1) in Group I (n = 30), propofol 2 mg kg(-1) in Group II (n = 30), and propofol 3.5 mg kg(-1) in Group III (n = 30). Then succinylcholine 1 mg kg(-1) was administered to the patients for intubation. RESULTS: Fasciculation was absent in 20% of Group III patients, and no vigorous fasciculation occurred in this group. Furthermore, the severity of fasciculation in Group III was significantly lower than in the other two groups (P = 0.01). Seventy per cent of patients had no myalgia in Group III, 39.2% in Group II and 37% in Group I (P = 0.007). Severity of myalgia was also significantly lower in Group III compared with the other two groups (P = 0.011). Post-operative creatine kinase levels were significantly higher than their baseline values in Groups I and II (P < 0.0001). CONCLUSION: Administration of propofol 3.5 mg kg-1 is effective in reducing fasciculations and myalgia after succinylcholine.

Succinylcholine-induced fasciculations in denervated rat muscles as measured using 31P-NMR spectroscopy: the effect of pretreatment with dantrolene or vecuronium.

BACKGROUND: We have previously demonstrated by 31P nuclear magnetic resonance (NMR) that succinylcholine (SCh) induces metabolic changes in denervated muscle. To specify those changes, we attempted to inhibit them using two different kinds of drugs, dantrolene and vecuronium. METHODS: Three weeks after unilateral sciatic nerve section, 75 male Wistar rats were randomly assigned to one of the following 5 groups: (1) non-pretreated normal muscle group; (2) non-pretreated denervated muscle group; (3) denervated muscle group pretreated with a low dose of vecuronium (0.02 mg.kg(-1)); (4) denervated muscle group pretreated with a high dose of vecuronium (0.2 mg.kg(-1)); (5) denervated muscle group pretreated with dantrolene (2 mg.kg(-1)). The change of the inorganic phosphate/phosphocreatine (Pi/PCr) ratio of each muscle was measured by 31P-NMR before and after SCh (1 mg.kg(-1)) administration and the corresponding peak amplitude of the electromyograms (EMG) was determined. RESULTS: The high dose of vecuronium totally inhibited SCh-induced fasciculation on EMG (100%-->2%). In this group, though the Pi/PCr ratio significantly increased 10 min after SCh, the peak after 5 min disappeared. The inhibition with dantrolene was about the same order of magnitude as with the low dose of vecuronium (35%:21%). However, the increase in the Pi/PCr only lasted about 10 min, in contrast to the other drugs. CONCLUSION: Our findings indicate that the Pi/PCr increases 5 and 10 min after SCh, respectively, as a result of two different processes. The first peak is caused by an excessive energy consumption in response to excessive muscle contraction. This in turn triggers the second peak, caused by breakdown of glycogen, initiated by an increased Ca2+ concentration.

Autoantibodies detected to expressed K+ channels are implicated in neuromyotonia.

Antibody-mediated autoimmunity underlies a diverse range of disorders, particularly in the nervous system where the extracellular domains of ion channels and receptors are especially vulnerable targets. We present here a novel means of detecting autoantibodies where the genes of the suspected target proteins are known, and use it to detect specific autoantibodies in acquired neuromyotonia (Isaacs' syndrome), a disorder characterized by hyperexcitable motor nerves and sometimes by central abnormalities. We expressed different human brain voltage-gated potassium channels in Xenopus oocytes by injecting the relevant alpha-subunit complementary RNA, and detected antibody binding by immunohistochemistry on frozen sections. Antibodies were detected to one or more human brain voltage-gated potassium channel in 12 of 12 neuromyotonia patients and none of 18 control subjects. The results establish neuromyotonia as a new antibody-mediated channelopathy and indicate the investigative potential of this molecular immunohistochemical assay.

The Effect of Diazepam and Midazolam Pretreatment on Succinylcholine Induced Fasciculation , Muscle Relaxation and Serum Potassium and Creatine Phosphokinase Changes / 대한마취과학회지

It has been already reported that diazepam pretreatment attenuated succinylcholine(Sch)-induced myalgia, fasciculation and potassium elevation. The effect of midazolam, a benzodiazepine derivative like diazepam, on Sch has not been investigated. So Midazolam, d-Tubocurarine and diazepam pretreatment were studied to determine the effect on subsequently administered Sch in 36 female patients. The patients were divided into 4 groups. Group 1 received no pretreatment, only Sch 1mg/kg(control). While Group 2 received d-Tubocurarine 0.05mg/kg, Group 3 received diazepam 0.05 mg/kg, and Group 4 received midazolam 0.025 mg/kg. After the pretreatment 4 minutes before Sch administration, the time to abolition and recovery of twitch height, the degree of fasciculation, the adequacy of relaxation for intubation, the changes in serum potassium and creatine pliosphokinase(CPK) were measured. The results are as follows: I) Group 2 showed increased time to abolition of twitch and decreased time to recovery of twitch. Group 3 showed increased time to recovery of twitch. 2) The incidence of fasciculation was decreased in Groups 2, 3 and 4. 3) Serum potassium was increased in Groups 1 and 2 but not in Groups 3 and 4. 4) Serum creatine phosphokinase was in- creased in all groups at post-Sch. 24 hours. It is concluded that diazepam and midazolam pretreatment attenuate Sch-inducedifasciculation and potassium increase.

What`s the optimal timing of pretreatment with pancuronium before succinylcholine to prevent muscle fasciculation? / 대한마취과학회지

Succinylcholine(SCh)-induced muscle fasciculations may be prevented by pretreatment with small doses of nondepolarizing muscle relaxants. The optimal timing of pretreatment to abolish fasciculation varies according to the drug used and dose. In this study, we determined the optimal timing of pretreatment of pancuronium to prevent muscular fasciculation in 100 patients. Each group (n=20) was received pancuronium 0.015 mg/kg at 1, 2, 3, 4, 5 minutes before SCh 3 mg/kg administration, respectively. The degree of fasciculations after SCh administration was observed and classified into one of 4 grade. There were significant differences between each groups (Ridit scores=10.078, p<0.01) To compare observed fasciculations of one grpup with those of the others, the degree of fasciculations was summed according to an arbitrary scale. The summation of grade in 4 minute group was lowest in this scale. It was concluded that the optimal timing of pretreatment, pancuronium 0.015 mg/kg, was 4 minutes before SCh 3 mg/kg injection.

The Effect of Small Dose of Nondepolarizing Muscle Relaxant Administered Prior to Succinylcholine on Intubating Condition / 대한마취과학회지

Subparalyzing dose of nodepolarizing relaxants prior to injection of succinylcholine has been used to prevent various adverse effects induced after succinylcholine. For investigating interactions between succinylcholine and small doses of four non-depolar-izing agents, the 112 subjects that were ASA class 1-2 and no existing neuromuscular conduction system disorder were divided into 5 groups that were control group(only succinylcholine 1 mg/kg) and pretreated group d-tubocurarine 0.5 mg/kg, atracurium 0.08 mg/kg, vecuronium 0.01 mg/kg and pancuronium 0.01 mg/kg. In each group, the plasma concentration of K+ and PChE before and after use of succinylcholine, fasciculation, onset and recovery time of succinylcholine block and intubating conditon were observed. The results are as follows; In the pretreated group, there were no significant changes of plasma concentration of K+ and plasma cholinesterase(Table 3) but diminished the incidence of fascieulation, delayed the onset time and shorted the recovery time of succinylcholine block(Table 4), and worse in intubating condition(Table 5) except pancuronium treated group. It was concluded that these seem to make worse condition of intubation, while small doses of nondepolarizing muscle relaxants except pancuronium antagonize depolarizing muscle relaxant.

The Effect of Small Dose of Nondepolarizing Muscle Relaxant Administered Prior to Succinylcholine on Intubating Condition / 대한마취과학회지

Subparalyzing dose of nodepolarizing relaxants prior to injection of succinylcholine has been used to prevent various adverse effects induced after succinylcholine. For investigating interactions between succinylcholine and small doses of four non-depolar-izing agents, the 112 subjects that were ASA class 1-2 and no existing neuromuscular conduction system disorder were divided into 5 groups that were control group(only succinylcholine 1 mg/kg) and pretreated group d-tubocurarine 0.5 mg/kg, atracurium 0.08 mg/kg, vecuronium 0.01 mg/kg and pancuronium 0.01 mg/kg. In each group, the plasma concentration of K+ and PChE before and after use of succinylcholine, fasciculation, onset and recovery time of succinylcholine block and intubating conditon were observed. The results are as follows; In the pretreated group, there were no significant changes of plasma concentration of K+ and plasma cholinesterase(Table 3) but diminished the incidence of fascieulation, delayed the onset time and shorted the recovery time of succinylcholine block(Table 4), and worse in intubating condition(Table 5) except pancuronium treated group. It was concluded that these seem to make worse condition of intubation, while small doses of nondepolarizing muscle relaxants except pancuronium antagonize depolarizing muscle relaxant.

The Effect of Succinylcholine on the Duration of Action of Pancuronium / 대한마취과학회지

For the assessment of the effect of succinylcholine(SCh) on pancuronium, 62 adult patients undergoing elective surgery under gerieral anesthesia were subjected tc this study in which the EMG response(twitch hight) of the hand to TOF stimulation(0.2 Hz) of ulnar nerve was monitored and recorded with Datex Relaxograph. According to the amount and mode of the drugs administered, the patients were divided into four experimental groups: 1) Group I, a bolus intravenous injection of pancuronium in dose of 0.05 mg/kg. 2) Group II, intravenous injection of pancuronium 0.1 mg/kg, a double dose of group I. 3) Group III, intravenous injection of pancuronium(0.05 mg/kg) after 25 to 50 recovery of initial twitch height from twitch height depression induced by SCh(1 mg/kg). 4) Group IV, mixed intravenous injection of SCh(1 mg/kg) and pancuronium(0.05 mg/kg). Followings were the results. 1) Mean onset time of the effect of pancuronium, was 15.6+/-1.1 minutes in group I and 13.8+/-1.5 minutes in group II, to 2,9+/-0.4 and 1.3+/-0.1 minutes in group III and IV respectively, and decreased(p< 0.001). 2) Duration of action of pancuronium was 47.1+/-4.5 minutes in group I and 87.7+/-7.4 minutes in group II, the prolongation of the latter being significantg<0.001). It was, however 48.3+/-5.2 minutes in group III, indicating that SCh showed a little effect, while it was 21.2+/-1.9 minutes in group IV, being significantly shorter than those of group I and III(p<0.001), 3) Potency of pancuronium expressed by the percentage changes of initial twich height was 34.3+/-6.0% in group I and it was noted to decrease significantly to 4.0+/-1.0% in group II and 0% in group IV(p<0.001). This pattern of decrease was almost similar to group II. 4) Presence of pancuronium(0.05 mg/kg) in group IV did not have any effect on the intensity of fasciculation induced by SCh. These results indicate that succinylcholine could potentiate the onset time and action potency of pancuronium by facilitating quick action on the receptor, but it have an antagonistic effect on the duration of action of pancuronium.

Neuromuscular pharmacology in rat neonates: development of responsiveness to prototypic blocking and reversal drugs.

The neonatal pharmacology of neuromuscular drugs was studied in vivo in newborn rats and in vitro in neonatal phrenic nerve-hemidiaphragm preparations. Drugs used to probe neuromuscular development in rat neonates were physostigmine, edrophonium, neostigmine, 4-aminopyridine, d-tubocurarine (dTc), and succinylcholine. The prejunctional actions of these drugs were monitored in relation to neonatal age by the appearance of stimulus-evoked repetitive discharge initiated by motor nerve endings and the occurrence and magnitude of the resulting enhancement of twitch tension. The occurrence and incidence of drug-induced fasciculations also served to track the development of functional motor nerve endings. Each of these prejunctional actions was inoperative until the third neonatal week, indicative of incomplete motor nerve development. In contrast, 4-aminopyridine, a nonanticholinesterase, evoked these prejunctional actions in 1-wk-old rat neonates. Neostigmine and edrophonium antagonized dTc as early as the first week; presumably, postsynaptic maturation had reached a functional level. 4-Aminopyridine also antagonized dTc at week 1. Rat neonates showed resistance to dTc blockade when tested by neonatal phrenic nerve-hemidiaphragm preparations in vitro. Relationships between age and 85%-95% transmission block declined to the adult level by week 5. This result indicates that in rat neonates, pharmacodynamic rather than pharmacokinetic mechanisms predominate in the development of responsiveness to dTc.

Rapid-sequence intubation of head trauma patients: prevention of fasciculations with pancuronium versus minidose succinylcholine.

INTRODUCTION: Fasciculations during rapid-sequence intubation may lead to increased intracranial pressure and emesis with aspiration. Standard rapid-sequence intubation requires a nondepolarizing blocking agent before succinylcholine administration. HYPOTHESIS: Prevention of fasciculations during rapid-sequence intubation of head trauma patients can be accomplished as safely and effectively with minidose succinylcholine as with a defasciculating dose of pancuronium. DESIGN: A prospective, randomized, double-blind study. SETTING: An inner-city county trauma center with 70,000 patient visits per year. PARTICIPANTS: Sequential adult head trauma patients requiring rapid-sequence intubation who had no contraindications to succinylcholine or pancuronium. INTERVENTIONS: Each head trauma patient requiring rapid-sequence intubation who met the inclusion criteria received standard rapid-sequence intubation maneuvers and lidocaine (1 mg/kg) IV. Patients were randomized to receive either minidose succinylcholine (0.1 mg/kg) or pancuronium (0.03 mg/kg) IV one minute prior to the full paralytic dose of succinylcholine (1.5 mg/kg) IV. Fasciculations were recorded using a graded visual scale. RESULTS: Of 46 patients, eight of 19 (42%) in the pancuronium group and six of 27 (22%) in the succinylcholine group experienced fasciculations. No statistically significant difference in fasciculations was detected between the two groups using chi 2 analysis. Complete relaxation of the cords was present in all but two patients, one in each group. No patient in either group experienced emesis or significant dysrhythmias. CONCLUSION: Pretreatment with minidose succinylcholine causes no greater incidence of fasciculations than pancuronium in rapid-sequence intubation of head trauma patients in an ED setting. Thus succinylcholine may be used as the sole paralytic agent in rapid-sequence intubation of head trauma patients.

The Effects of Non - depolarizing Neuromuscular Blockers on the Succinylcholine Induced Muscle Fasciculation , Postoperative Musle Pain and Relaxation / 대한마취과학회지

To study the effects of small amounts of non-depolarizing neuromuscular blockers on the muscle fasciculation, postoperative muscle pains and relaxation time by succinylcholine, three groups of patients were pretreated with vecuronium (0.01 mg/kg), pancuronium (0.015 mg/kg) and gallamine (0, 2 mg/kg) 3 minutes before succinylcholine injection, respectively and compared their results with control group-saline pretreated group. The results are as follows; 1) Intensity of muscle fasciculation deereased significantly in all groups with non-depolarizing neuromuscular blockers, and frequency had the fewest in pancuronium pretreated group than the others. 2) Intensity of postoperative muscle pains decreased significantly in groups pretreated with pancuronium and gallamine, and frequency had the fewest in gallamine pretreated group than the others. 3) Pretreatment with non-depolarzing neuromuscular blocker had no effects on the onset time of muscle relaxation of succinylcholine but recovery of muscle relaxation by succinylchoine was more rapidly occured than control group. Above results, it will be suggest that gallamine and pancuronium can be used more effectively to prevent muscle fasciculation and postoperative muscle pain without influence on succinylcholine-induced muscle relaxation.

The Effects of the Small Doses of Nondepolarzing Muscle Relaxants Administered Just Prior to Succinylcholine on Intragastric and Intraocular Pressures / 대한마취과학회지

Succinylcho1ine(Sch) may provoke regurgitation of gastric contents by producing fasciculations of abdominal musculatrue, which in turn may increase intragastric pressure. And it has been also believed that Sch increases intraocular pressure in part by contracture of the extraocular muscles. The purpose of this study was to determine whether these increases and the degree of fasciculation could be reduced by prior administration of a nondepolarizing muscle relaxant. Simultaneous administration of pancuronium or vecuronium with Sch significantly reduced the degree of fasciculation and also decreased the elevation of the intragastric pressure, but did not show any remarkable effect on the intraocular pressure, We might say that wed better use the small amount of nondepolarizing muscle relaxant with Sch to prevent the increase of intragastric pressure, thereby decrease the chance of regurgitation and aspiration during induction period.