Pholcodine consumption and immunoglobulin E-sensitization in atopics from Australia, Korea, and Japan

BACKGROUND: Accumulating data indicates that pholcodine (PHO)-consuming countries have higher sero-prevalences of immunoglobulin E (IgE)-antibodies to PHO and suxamethonium (SUX) and increased frequencies of IgE-mediated anaphylaxis to neuromuscular blocking agents (NMBAs) than nonconsuming. Withdrawing PHO-containing cough syrups resulted in a significant decrease of cases with anaphylaxis in Scandinavia. Nevertheless, the European Medicines Agency in 2011 advised to continue the unrestricted use throughout the European Union. OBJECTIVE: To extend studies on PHO consumption and prevalence of IgE-sensitization to morphine (MOR), PHO, and SUX to countries representing high (Australia), and low (Korea and Japan), consumers, respectively. METHODS: IgE-antibodies to SUX, MOR, and PHO in atopic subjects were determined by immunoassay and compared with official figures for PHO consumption and reported anaphylaxis to NMBA. RESULTS: The prevalences of IgE-antibodies to PHO, MOR, and SUX were 10%, 8.6%, and 4.3%, respectively, in Australia. The corresponding figures for Japan were 0.8%, 0.8%, and 1.5%, and for Korea 1.0% to PHO and 0.5% to MOR and SUX. Of the SUX-positive sera, 100% were positive to PHO or MOR in Australia and 0% in Japan and Korea. CONCLUSION: The study supports previous findings; exposure to PHO may induce IgE-antibodies to the substituted ammonium ion epitope of NMBAs, thus increasing risk of NMBA-induced anaphylaxis considerably. However, other, still unknown factors occasionally might induce IgE-antibodies to SUX.

A Case of Neonatal Tetanus Cured with Neuromuscular Blocking Agent and Ventilatory Support

A neonate born at 38 gestational weeks was admitted due to generalized tonic-clonic seizure and cyanosis. The neonate was born six days previously at home through normal delivery and the umbilical cord was cut using scissors sterilized in boiling water. The neonate weighed 3,180 g at admission. Physical examination revealed cyanosis, opisthotonus, trismus and reactive muscle spasms. Laboratory exam, brain sonogram and EEG showed no significant abnormal findings. Based on her history and physical examination, the neonate was diagnosed with tetanus and put in an incubator isolated in a quiet, dark room. Treatment with tetanus human immunoglobulin along with antibiotics (penicillin G) were started immediately, and mechanical ventilation, administration of neuromuscular blocking agent and muscle relaxant were also started off. The frequency of seizure episode decreased gradually, and on the 32nd hospital day, mechanical ventilatory support was stopped along with extubation two days later. Thereafter, the neonate was in continuous generalized hypertonic state and showed feeding difficulty, but there was gradual improvement. She was dismissed on the 49th hospital day and is currently under OPD follow-up, doing well with no special problems. Respiratory management is critical to neonatal tetanus. We report here a case of tetanus treated with inhibition of self-respiration, neuromuscular blocker and application of ventilator, and present this method as a useful direction for future treatment of neonatal tetanus.

The Duration of Action of Additional Doses of Pipecuronium is not affected by the Size of the Initial Dose / 대한마취과학회지

The neuromuscular blocking effect of pipecuronium was evaluated in 35 patients under N2O-O2-isoflurane anesthesia with visual and/or tactile counts for the twitch of the adductor pollicis muscle in response to train-of-tour(TOF) stimulation of the ulnar nerve at the wrist. Group I, II and III were classified according to the initial dose of pipecuronium of 50, 80 and 100ug/kg, respectively. The additional dose, 30 ug/kg, was given in all three groups when the first twitch of TOF(T) reappeared. The onset time in Group I, II and III was 361.4+/-98.6, 218.7+/- 80.8 and 239.0+/-73.7 seconds, respectively. The onset time in Group I was significantly slower(p<0.005) than those in the other groups. All three doses of pipecuronium provided good to exceUent intubating condition in about 4 to 6 minutes after the administration of the initial dose. The time interval from the disappearance of T1 to the reappearance of T1 was 39.0+/-20.8 min in Group I, which was significantly longer(p<0.05) in Group II(67.7+/-26.4 min) or III(63.8+/-20.8 min). The cumulative effect of pipecuronium was evaluated by comparing the mean time intervals of an additional dose to the succeeding ones. The intervals between additional doses were independent of the size or duration of the initial dose. There were no significant differences in the intervals between additional doses. Heart rates, rhythms and mean arterial blood pressures were not significantly changed in any groups following the administration of pipecuronium In conclusion, pipecuronium bromide can be recommended as a long-acting neuromuscular blocking agent with an absence or minimum of cumulative and cardiovascular effects for patients in whom a long operation is scheduled and the cardiovascular stability is required.

Comparison of Pharmacokinetic Affinity of Various Non-depolarizing Neuromuscular Blocking Agents in the Isolated Foream / 대한마취과학회지

It is well known that the plasma concentration is important in determining the rate of recovery from neuromuscular block. However, nondepolarizing neuromuscular blockade are retained at the neuromuscular junction and are not readily displaced in response of changes in plasma drug concentration, for instance, the neuromuscular block induced by mivacurium appears to considerably outlast the theoretical plasma half-life of the drug and is continued long after the plasma level has fallen to subparalytic levels due to rapid metabolism by pseudocholinesterase. It has been suggested that although plasma concentration may be the key determinant of recovery from neuromuscular block, recovery will depend upon the dissociation from the affinity of drug in the effect compartrnent and not upon its plasma concentration. In an attempt to confirm these evidences, we have investigated the response of changes in neuromuscular block after releasing tourniquet at 50% twitch depression using the isolated forearm experiment with various neuromuscular blocking agents. The results of this study demonstrated the further increase of block after early toumiquet release in the isolated forarm in all agents; 66+/-14% in vecuronium, 90+/-9% in atracurium, 92+/-7% in pancuronium, and 73+/-18% in mivacurium Conclusively, the further block continued to increase in spite of the negligible plasma drug concentration after early tourniquet release may be caused by more in affinity of drugs in binding sites than plasma drug concentration. Therfore, it is evident that both the affinity of drug to the receptor and the plasma drug concentration have influenced on the recovery from the neuromuscular block.

Comparison of Neuromuscular Blocking Effects of Mivacurium and Atracurium in Adult Patients during H2O-ropofol-Fentanyl Anesthesia / 대한마취과학회지

The neuromuscular blocking effsct of mivscurium 0.15mg/kg and atracurium 0.5mg/kg were compared in 17 adult patients (ASA class I and II) during N2O propofol-fentanyl anesthesia. Neuromuscular transmission was monitored by recording the compound electromyogram of the hypothenar muscles resulting from supramaximal train of four stimulation applied to the ulnar nerve. Neuromuscular block was recovered spontaneously in all cases. Onset time of over 95% block was not different significantly between mivacurium and atraeurium (201+/-37.6vs 176.6+/-28.5sec, p>0.05, mean SD). Duration from injection of mivacurium to 25% recovery of control twitch height was significantly shorter than that of atracurium (13.0+/-2.2vs 38.8+/-4.9min, p<0.05). The recovery index was also significantly shorter for mivacurium than for atracurium (6.9+/-1.1vs 14.5+/-53.0min, p<0.05). In conclusion, we have confirmed that duration and recovery of action of mivacurium were shorter than those of atracurium, but onset times of both agents were not different.

The Neuromuscular Blocking Actions of Metocurine and its Reversal in Cats with Acute Renal Failure / 대한마취과학회지

Acute renal failure was induced to investigate it effects on the neuromuscular blocking actions and reversals of metocurine in 14 adult cats, either sex, weighing 2.5-4.5 kg. Ligation of both renal pedicles in 6 cats (Group II) and its sham operations in 8 cats (Group I) were done under the pentobarbital anesthesia. Neuromuscular monitoring was done using a common peroneal nerve-tibialis anterior muscle preparation. The mean blood pressures, acid-base status and serum electrolytes at the time of injection of metocurine or neostigmine were not significantly different between two groups. The heart rates at the administration of neostigmine were significantly decreased probably due to the decreased body temperatures in group I. The onset time of metocurine with 3 X ED95 in acute renal failure was simiiar to that in normal renal function. However, the duration of metocurine with 3 X ED95 in acute renal failure was significantly longer that that in normal renal function. The effeets of neostigmine administered at 15%-spontaneous twitch recovery for the recovery indices and antagonism effects were not significantly different between two groups. In conclusion, acute renal failure prolongs the duration of metocurine, but not interfere its onset. Additionally, there is no effect on the reversal actions of neostigmine if administered at the spontaneous recovery of twitch height more than 15%.

Effect of Propofol on the Neuromuscular Transmission and Vecuronium-induced Muscle Relaxation / 대한마취과학회지

To investigate the effect of propofol in emulsion on the neuromuscular transmission and on the interaction with muscle relaxant, 31 adult parients, ASA I or II, were studied. Neuromuscular transmission was monitored continuously using a train-of-four(TOF) stimulation at every 20 seconds. The ulnar nerve was stimulated supramaximally through surface electrodes at a rate of 0.1 msec, 2Hz and the evoked compound action potential of hypothenar muscles was measured automatically with Relaxograph0atex). To determine the interaction of propofol with muscle relaxant, a bolus injection of propofol 2.5 mg/kg was given intravenously during a steady-state neuromuscular blockade of vencuronium and the effect on the twitch height measured for 30 minutes in 16 patients. To determine the action of propofol on neuromuscular transmission without muscle relaxant in 15 patients, propofol 20(n=7) or 40mg(n=8) in 10ml of 5% dextrose in water was injected respectively at isolated arm of which circulation was occluded by forearm pneumatic tourniquet and TOF response was measured for 10 minutes. In the results, propofol 2.5 mg/kg intravenous administration during steady-state neuromus- cular blokade of vecuronium did not show any change in the twitch height for 30 minutes. Propofol both 20 mg and 40 mg injected to isolated arm also did not show changes in first twitch height and train-of-four ratio for 10 minutes. Conclusively, propofol in emulsion does not interact with vecuronium at clinical dose, and also has not any effect on neuromuscular function at even high dose.

Effect of Propofol on the Neuromuscular Transmission and Vecuronium-induced Muscle Relaxation / 대한마취과학회지

To investigate the effect of propofol in emulsion on the neuromuscular transmission and on the interaction with muscle relaxant, 31 adult parients, ASA I or II, were studied. Neuromuscular transmission was monitored continuously using a train-of-four(TOF) stimulation at every 20 seconds. The ulnar nerve was stimulated supramaximally through surface electrodes at a rate of 0.1 msec, 2Hz and the evoked compound action potential of hypothenar muscles was measured automatically with Relaxograph0atex). To determine the interaction of propofol with muscle relaxant, a bolus injection of propofol 2.5 mg/kg was given intravenously during a steady-state neuromuscular blockade of vencuronium and the effect on the twitch height measured for 30 minutes in 16 patients. To determine the action of propofol on neuromuscular transmission without muscle relaxant in 15 patients, propofol 20(n=7) or 40mg(n=8) in 10ml of 5% dextrose in water was injected respectively at isolated arm of which circulation was occluded by forearm pneumatic tourniquet and TOF response was measured for 10 minutes. In the results, propofol 2.5 mg/kg intravenous administration during steady-state neuromus- cular blokade of vecuronium did not show any change in the twitch height for 30 minutes. Propofol both 20 mg and 40 mg injected to isolated arm also did not show changes in first twitch height and train-of-four ratio for 10 minutes. Conclusively, propofol in emulsion does not interact with vecuronium at clinical dose, and also has not any effect on neuromuscular function at even high dose.

The Effect of Corticosteroids on the Recovery Index of Neuromuscular Blockade / 대한마취과학회지

Several investigators have described an interaction between muscle relaxants and corticosteroids which have showed different results. The exact mechanism of this section is not clear and there conflicting results have further confusion. For the confirmation on how to interact these two drugs in patients without influencing factors to the neuromuscular transmission, corticosteroids(hydrocortisone, methyl prednisolone) 0.5mg/kg and 5.0 mg/kg mixed in 20ml of normal saline with micro-dose of various muscle relaxants(vecuronium 0.1mg/kg/30, d-Tubocurarine 0.4mg/kg30, succinylcholine 1mg/kg/30) were administered respectively into the vein at the distal portion of a pneumatic tourniquet applied on the upper arm with higher pressure than arterial pressure. This was to study the dose response according to recovery time between the experimental troup and the control group. Neuromuscular block was measured by recording the twitch response following ulnar nerve stimulation by EMG(ABM, Datex Co., 2Hz 30 mA supermaximal voltage). And at over 95% depression of the twitch height, following administration of muscle relaxants alone(control group) or muscle relaxants combined with corticosteroids(study group), the tourniquet was released, and recovery time from 25% to 75% recovery of twitch height was measured according to recovery index(RI). The results obtained were as follows: 1) In the group which 0.5mg/kg of hydrocortisone was administered. the RI of vecuronium and d-tubocurarine was shorten to 3.47+/-1.43 and 9.30+/-1.48 minutes, and in hydrocortisone 5.0mg/kg, was prolonged to 12.30+/-2.18 and 17.96+/-0.62 minutes, compared with control group(8.08+/-1.48 in vecuronium and 13.43+/-2.32 in d-Tubocurarine). 2) Methyl prednisolone also tended to short the RI in 0.5 mg/kg of corticosteroids and to prolong in 5.0 mg/kg, but not significant. 3) Corticosteroids not to depend on dose prolonged the RI from succinylcholine induced neuromuscular blocks. 4) Plasma cholinesterase values following injection of hydrocortisone 0.5mg/kg and 7.0mg/kg were not changed significantly. 5) Hydrocortisone alone had significant effect on twitch tension, increased in dose of 0.5mg/kg and depressed in dose of 5.0mg/kg. Conclusively, in the interaction between corticosteroids and muscle relaxants, a combined effect of antagonism in small dose and enhancement in large dose of corticosteroids to non-depolarizing neuromuscular blocking action and a potenciated effect to depolarizing neuromuscular blocking action, seems to be possible. We recommend careful monitoring of neuromuscular transmission in patients receiving corticosteroids when neuromuscular blocking agents in used for muscle relaxation.