Respiratory function in children during recovery from neuromuscular blockade

Residual neuromuscular blockade is a major risk factor for respiratory insufficiency. We examined the relationship between neuromuscular and respiratory function in 18 ASA I or II children aged 2–4 years. Lung function was measured by pneumotachography and transpulmonary pressure, neuromuscular transmission by first twitch response ratio (T1:T1) and train-of-four ratio (TOFR), before and at specific points in recovery from vecuronium paralysis. The tidal volume was directly related to maximal inspiratory pressure at occlusion ( P _Iocc), P <0.001, whereas the minute ventilation (V_E) was related to the respiratory drive (P0.1), P <0.001. The best predictors of minute ventilation were the P0.1 ( r =0.57), and the TOFR ( r =0.62). P _Iocc and P0.1 correlated closely ( r =0.889, P =0.002) but TOFR and T1:T1 did not correlate with either. Our results show that the occlusion pressure measurements, P0.1 and P _Iocc, were good predictors of both V_E·kg⁻¹ and respiratory work.     

Isoflurane inhibits muscle fasciculations caused by succinylcholine in children

The incidence and intensity of muscle fasciculations as well as the occurrence of cardiac arrhythmias following succinylcholine were evaluated in 36 premedicated children (1.0–5.7 years) after intravenous induction with thiopentone or after inhalation induction with isoflurane (3.75 vol-% in 70% nitrous oxide in oxygen). The study was randomized. In the thiopentone group, fasciculations were seen in all children and in the isotlurane group in 5 of 18 children (P<0.001). The median of the duration of fasciculations was 15 s with a minimum of 5 s and maximum of 36 s (1st quartile 9 s and 3rd quartile 20 s) in the thiopentone group and 0 (0–15) s with a 1st quartile of 0 and a 3rd quartile of 3 s in the isoflurane group (P<0.001). No cardiac arrhythmias were noted in either group. In conclusion, isoflurane in nitrous oxide inhibits succinylcholine-induced muscle fasciculations in children.     

Spontaneous recovery of residual neuromuscular blockade after atracurium or vecuronium during isoflurane anaesthesia

With atracurium and vecuronium, spontaneous recovery of residual neuromuscular blockade monitored electromyographically during 0.5% isoflurane anaesthesia was studied in 60 patients undergoing plastic surgery. After thiopentone, in random order, either atracurium 0.5 mg kg-1 or vecuronium 0.1 mg kg-1 was administered and isoflurane added to N2O and O2 mixture. Following spontaneous recovery of both the single twitch amplitude (T1) to 75% of the control value and the train-of-four ratio (TOF ratio) to 75%, incremental doses of the relaxant were given to maintain the T1 at less than 10%. Before the end of surgery, the blockade was again permitted to recover spontaneously. During the initial spontaneous recovery, the mean recovery time of T1 from 25% to 75% (the recovery index) with atracurium was longer (P less than 0.001) than that with vecuronium (13.2 min and 10.1 min, respectively) but, during the second recovery, the mean recovery index was shorter (P less than 0.05) with atracurium than with vecuronium (16.1 min and 19.8 min, respectively). The recovery time from T1 75% to TOF ratio 75%, indicating the recovery rate of residual neuromuscular blockade, with atracurium was about 15 min after both the initial and the second recoveries. With vecuronium, the respective recovery times were significantly (P less than 0.001) longer (25.6 min and 38.5 min, respectively). It is concluded that with vecuronium there is slower spontaneous recovery of residual neuromuscular blockade than with atracurium.     

Evaluation of twitch responses obtained from abductor hallucis muscle as a monitor of neuromuscular blockade: Comparison with the results from adductor pollicis muscle

The twitch responses evoked from the abductor hallucis muscle (AHM) and the adductor pollicis muscle (APM) were examined simultaneously in 20 anesthetized patients following a single bolus intravenous administration of 0.04 mg·kg⁻¹ of vecuronium bromide. The mean onset time of vecuronium-induced depression of AHM twitch responses was significantly slower than that of APM twitch responses (4.9±1.5 minvs 3.7±1.2 min, mean±SD,P<0.001), and when the clinical duration times of vecuronium were compared, AHM twitch responses recovered more quickly than APM twitch responses (15.3±4.1 minvs 19.6±6.7 min,P<0.01), although there was no statistically significant difference in the spontaneous recovery time between AHM and APM (9.8±2.9 minvs 10.0±3.6 min). It is concluded that the twitch responses of AHM may be a useful monitor of neuromuscular blockade in anesthetized patients in whom setting the blockade monitor on the patient's arms is difficult, although monitoring of twitch response of AHM is less sensitive than that of APM in case of vecuronium administration.     

Changes in serum potassium, calcium and creatine kinase following suxamethonium administration in children with and without strabismus

The immediate changes in serum potassium and calcium and 24-h changes in creatine kinase (CK) following suxamethonium administration were compared in children undergoing strabismus repair or tonsillectomy following induction of anaesthesia with thiopentone or halothane. A separate group of children were anaesthetized with isoflurane and did not receive suxamethonium. There was a significant increase ( P < 0.05) in serum potassium of 0.26 and 0.56 mmolċ⁻¹ following halothane-suxamethonium induction and a significant decrease ( P < 0.05) of 0.35 and 0.13 mmolċ⁻¹ after thiopentone-suxamethonium induction in the strabismus and tonsillectomy groups respectively. There was an increase in the 24 h CK values of 624 and 694 uċl⁻¹ ( P < 0.05) in patients receiving halothane-suxamethonium induction and of 43 (NS) and 247 uċ⁻¹ ( P < 0.05) in patients receiving thiopentone-suxamethonium induction in the strabismus and tonsillectomy groups respectively. Suxamethonium administration was associated with a small but sometimes significant ( P < 0.05) decrease in total serum calcium concentrations (0.036 to 0.049 mmolċ⁻¹). Changes in all indices were minimal in children anaesthetized with isoflurane. It is concluded that the administration of halothane and suxamethonium is the main cause for the changes in serum potassium and CK and not the presence of strabismus.     

Carbon dioxide elimination in anaesthetized children

Carbon dioxide elimination (VCO2) was measured in 186 anaesthetized, spontaneously breathing infants and children with body weights ranging from 2.8 to 26.5 kg. They all underwent minor paediatric surgical procedures. The influence on VCO2 of age, operation, premedication, caudal anaesthesia, and different volatile anaesthetic agents was investigated. The volume of exhaled gas, during three- to five-minute collection periods, was measured and the fraction of exhaled CO2 was determined by a CO2 meter. Under basal anaesthetic conditions, the average output before operation followed the equation: VCO2 (ml.min-1) = -1.25X + 13.0X2, in which X = lne (body weight, kg). Expressed on a weight basis, the youngest infants (weighing less than 5 kg) had the lowest VCO2. Higher values were measured up to a body weight of 10 kg above which a negative correlation occurred between VCO2 (ml.min-1.kg-1) and body weight. The use of premedication resulted in a more variable VCO2 during operations than when opioid premedication was not used. The combination of a general anaesthetic and caudal anaesthesia stabilized VCO2. Also, children anaesthetized with halothane had a higher VCO2 than those who were anaesthetized with enflurane or isoflurane (P less than 0.05). The variable VCO2 emphasizes the need for increased monitoring of VCO2 during routine anaesthesia and operation in infants and children.     

Comparison of isoflurane and halothane on recovery from neuromuscular blockade using atracurium in infants with hepatic dysfunction undergoing major abdominal surgery

The effects of either isoflurane or halothane on recovery from neuromuscular blockade with atracurium in infants with hepatic dysfunction undergoing major abdominal surgery were studied. Neuromuscular blockade was assessed visually at minute intervals by 'train-of-four' using supra-maximal stimuli. The times to first and second increment and total requirement of atracurium in two groups of infants randomly allocated to receive either isoflurane or halothane for induction and supplementation were recorded. Fourteen patients completed the study, seven with isoflurane and seven with halothane. No evidence was found that recovery from neuromuscular blockade with atracurium was prolonged by isoflurane as compared to halothane.     

Mivacurium infusion requirement and spontaneous recovery of neuromuscular transmission in children anaesthetized with nitrous oxide and fentanyl,halothane, isoflurane or sevoflurane

BACKGROUND: Forty children, aged 3-11 years, ASA I or II, were allocated at random to receive N2O/O2-fentanyl or 1 MAC halothane, isoflurane or sevoflurane-N2O/O2 anaesthesia. Mivacurium was used for muscle relaxation. METHODS: Electromyographic response of the adductor pollicis to train-of-four (TOF) stimulation, 2 Hz for 2 s, applied to the ulnar nerve at 10-s intervals was recorded using the Relaxograph (Datex, Helsinki, Finland). An intubating dose of mivacurium, 0.2 mg.kg-1 was given, and when T1 returned to 5%, muscle relaxation was maintained by continuous infusion of mivacurium, adjusted manually to maintain a stable 90-99% block. RESULTS: Halothane, isoflurane and sevoflurane groups had lower infusion requirements for mivacurium than the N2O-fentanyl group (P=0.000083). Mivacurium requirement was 18.8 +/- 6.8, 10.8 +/- 4.2, 6.9 +/- 3.9 and 9.6 +/- 5.6 microg.kg-1.min-1 for children receiving N2O/O2-fentanyl, halothane, isoflurane and sevoflurane anaesthesia, respectively. CONCLUSIONS: Spontaneous recovery from T1=10% to TOF ratio=0.7 was insignificantly prolonged from 6.3 to 12.5 min in the fentanyl group to 7-16.5 min in children anaesthetized with inhalational anaesthetics.     

The Bispectral Index in children: comparing isoflurane and halothane

Background. The Bispectral Index (BIS) has been calibrated forseveral general anaesthetic agents including isoflurane. Halothaneis still used in paediatric anaesthesia. Compared with othervolatile anaesthetics, halothane has a different receptor affinityand differing effects on the EEG. There are limited data evaluatingthe BIS with halothane. We set out to compare the BIS usinghalothane and isoflurane at a clinically relevant equipotentconcentration (1 MAC) and at a reproducible measure of anaestheticeffect (awakening). Methods. Forty children aged between 2 and 15 yr were enrolledin a masked randomized trial—20 in each group. Anaesthesiawas induced with sevoflurane or propofol. Either halothane orisoflurane were given to obtain an end-tidal concentration of1 MAC for 15 min. The BIS was then recorded. The BIS was alsorecorded at awakening. Values (mean (SD)) were compared witha t test. Results. At 1 MAC the BIS for halothane was significantly greaterthan isoflurane (56.5 (8.1) vs 35.9 (8.5), P<0.0001). Atawakening there was no significant difference (BIS halothane;81.1 (11.9), BIS isoflurane; 82.5 (16.4)). The difference inmeans at awakening was 1.4 (95% CI –8.2 to 11.1). Conclusions. At equipotent concentrations of halothane and isofluraneBIS valves were significantly greater with halothane. At awakeningthe BIS values were equivalent for each agent. This findingis consistent with the BIS being more affected by the agentused at higher concentrations of anaesthetic. The BIS must beinterpreted with caution when using halothane. Br J Anaesth 2004; 92: 14–17     

The effect of peripheral hypothermia on a vecuronium-induced neuromuscular block

Seven healthy patients were investigated during midazolam-fentanyl nitrous oxide-oxygen anaesthesia. The mechanical twitch response of the adductor pollicis muscle was recorded simultaneously during bilateral supramaximal train-of-four (TOF) stimulation of the ulnar nerves at the wrist. Intense neuromuscular block was evaluated using the post-tetanic count (PTC) method. Core temperature and the peripheral skin temperature of one arm were kept normal and stable. Following cooling of the other arm to a peripheral hand skin temperature of 27 degrees C, vecuronium was administered in a bolus dose of 0.05 mg.kg-1 followed by maintenance doses of 0.02 mg.kg-1. In the hypothermic and the normothermic arm the onset time following the bolus dose was 180 +/- 40 (mean +/- s.d.) seconds and 140 +/- 30 s, respectively, the duration of action was 26.4 +/- 4.5 and 16.5 +/- 4.0 min and the recovery time was 265 +/- 90 and 130 +/- 60 s (P less than 0.01). The time course of action following maintenance doses showed a similar marked difference between the hypothermic and the normothermic arm. In the normothermic arm a close correlation was found between the number of post-tetanic twitches and the time to first response to TOF stimulation. In contrast, in the hypothermic arm the number of post-tetanic twitches showed great variation with a poor correlation to the duration of intense neuromuscular block. It is concluded that the time course of action of a vecuronium-induced neuromuscular block is markedly prolonged during peripheral hypothermia and intense neuromuscular block cannot reliably be assessed using the PTC method at low peripheral temperature.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drive and timing components of respiration in young children following induction of anaesthesia with halo-thane or ketamine

Timing and drive components of respiration were studied in 18 young children following induction of anaesthesia with ketamine and were compared with results from ten children following induction of anaesthesia with halothane. During one minute of quiet breathing, signals from a pneumotachograph attached to the anaesthetic mask were analysed for tidal volume (Vt), respiratory frequency (f), minute volume (Ve), inspiratory and expiratory times (Ti, Te) and flow pattern. Following induction of anaesthesia with ketamine, children breathed more slowly and deeply than children receiving halothane, but there was no significant difference in Ve or in Vt/Ti, suggesting that respiratory drive was similar in the two groups of children. In the children receiving ketamine, Ti was more than twice as long, and thus the ratio Ti/Te was significantly increased, in comparison with the group receiving halothane. In addition to the prolonged Ti in the children induced with ketamine, there was a more rapid increase in volume in early inspiration than in late inspiration, which is an apneustic breathing pattern. There was a slower decrease in volume in early expiration, with occasional early expiratory breath holding lasting up to three seconds, in the ketamine-induced children. The unique breathing pattern demonstrated with ketamine, consisting of large Vt, increased Ti/Te ratio, apneustic inspiratory pattern, and expiratory braking, contributed to an increased mean lung volume above functional residual capacity, of 2.40 ml.kg-1 body weight, in comparison to 1.27 ml.kg-1 in the children receiving halothane.     

Alfentanil inhibits muscle fasciculations caused by suxamethonium in children and in young adults

The effect of alfentanil on suxamethonium-induced muscle fasciculations was studied in a double-blind study in 34 children (mean age 6.8 years) and in 30 adults (mean age 20 years). After pretreatment with either alfentanil 50 micrograms kg-1 or saline, each patient was anaesthetized with a sleep dose of thiopental followed by suxamethonium 1.5 mg kg-1 for endotracheal intubation. Compared to the control groups, alfentanil significantly decreased the intensity of visible muscle fasciculations caused by suxamethonium. In children, the duration of muscle fasciculations was shorter in the alfentanil than in the control group. In adults, the intensity rather than the duration of fasciculations was attenuated by alfentanil. The inhibition of fasciculations caused by alfentanil was also demonstrated in children in the surface electromyogram recorded on the biceps. There was no circulatory response to endotracheal intubation in the groups pretreated with alfentanil.     

The respiratory effects of isoflurane, enflurane and halothane in spontaneously breathing children

The respiratory effects of halothane, isoflurane and enflurane were assessed during nitrous oxide anaesthesia (N2O 50%) in three groups of unstimulated, spontaneously breathing children who weighed 10-20 kg and were aged 1-6 years. Respiratory variables were measured or calculated from capnographic and pneumotachographic recordings at three multiples of minimal alveolar concentration (MAC). The slope of the carbon dioxide response was measured. Similar increases in end tidal carbon dioxide were found for the three agents at each MAC multiple, and similar decreases in tidal volume and in the slope of the ventilatory response to carbon dioxide. A dose-related tachypnoea occurred with halothane and a significant decrease in the duration of inspiration and the duration of each breath at the deepest level of anaesthesia. A significant increase in both these times occurred with enflurane, and a decrease in respiratory rate. No change in respiratory rate occurred with isoflurane at increasing alveolar concentrations whereas at each level of anaesthesia inspiratory time was significantly reduced.     

Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents

Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.     

An audit of sedation, analgesia and muscle relaxation in paediatric intensive care in the United Kingdom

A questionnaire detailing four clinical cases (epiglottitis; head injury; aspiration pneumonitis and a neonate requiring postoperative pulmonary ventilation) was used to elicit the opinions of consultant paediatric anaesthetists in the UK regarding airway management, sedation level and drugs used in paediatric intensive care. Sixteen out of 18 replied. The preferred level of sedation varied and was deepest in head injury and lightest in epiglottitis. Airway management in epiglottitis most commonly involved a breathing system utilizing continuous positive airway pressure (CPAP). In the management of a head injury, a mixture of sedative, analgesic and muscle relaxant was preferred (15/16). Different combinations of drugs were preferred in managing the other three clinical cases. A majority of the participants (15/16) favoured intravenous infusions as the method of choice for drug delivery. Of the more recently introduced drugs, propofol was used occasionally or often in 11 units, compared with isoflurane and alfentanil in 1 and 4 units respectively. Complications from the long term use of many sedative drugs have been reported and constant vigilance is required to detect these effects.     

The effects of halothane and isoflurane on forearm blood flow in children as determined by venous occlusion plethysmography

Comparative studies have not been made of the peripheral vascular effects of halothane and isoflurane in children. Using a water-filled venous occlusion plethysmograph, measurements of forearm blood flow were made in 2 groups of 19 children exposed to increasing concentrations of these 2 agents. Halothane and isoflurane caused comparable and dose dependent increases in forearm blood flow and reductions in peripheral vascular resistance and arterial pressure. These findings suggest that, in younger children, reductions in peripheral vascular resistance are partly responsible for decreases in arterial pressure when lower concentrations of these agents are used.     

The influence of 10 mg and 20 mg of bambuterol on the duration of succinylcholine-induced neuromuscular blockade

Bambuterol is an inactive prodrug which is enzymatically cleaved by plasma cholinesterase to yield the active compound, terbutaline. This catalytic process is accompanied by a selective inhibition of plasma-cholinesterase, the enzyme also necessary for the break-down of succinylcholine. We therefore studied the possible effect of bambuterol on succinylcholine-induced neuromuscular blockade in a double-blind fashion in patients undergoing surgery under general anaesthesia. Of the 39 patients studied, 13 patients had 10 mg of bambuterol, 12 had 20 mg and 14 were given placebo 10-16 h prior to anaesthesia. Succinylcholine 1 mg.kg-1 bw was administered after induction of anaesthesia. Following supramaximal train-of-four stimulation of the ulnar nerve, the tension developed in the adductor pollicis muscle was measured. Onset time and the durations of action (times to 10%, 25%, 75% and 90% recovery of the first twitch of the train-of four response) were recorded. The mean recovery times were prolonged 30-50% in patients who had received 10 or 20 mg of bambuterol as compared with placebo. It is concluded that a prolonged duration of action of succinylcholine can be expected in patients being treated with bambuterol.     

Evaluation of a device for the measurement of the evoked tensions of the rectus abdominis muscle

A device was developed to measure the evoked tensions of the rectus abdominis muscle which consisted of a fluid-filled reservoir wedged between the rectus abdominis muscle and a self-retaining retractor. The evoked contractions of the rectus muscle were compared with that of the tibialis anterior muscle in twelve dogs anaesthetised with pentobarbitone. Significantly greater amounts of tubocurarine were required to depress the response to train-of-four stimuli and the twitch tensions of the rectus muscle than the tibialis. The tibialis recovered faster, spontaneously or after neostigmine, than the rectus in eight of the animals; the opposite occurred in the other four. The present device can be useful during surgery for the evaluation of abdominal muscle tension.     

The effect of halothane on mivacurium infusion requirements in adult surgical patients

Background: The extent of interaction between volatile anaesthetics and neuromuscular blocking agents depends both on the inhalational anaesthetic and the muscle relaxant. Halothane has the weakest potentiating effect on neuromuscular blocking drugs and previous studies of the interaction between halothane and mivacurium have been contradictory. We were interested in determining the effect of different levels of halothane-nitrous oxide anaesthesia on infusion requirements of mivacurium. Methods: Sixty adult surgical patients were studied. Anaesthesia was induced with thiopentone and fentanyl and intubation facilitated with mivacurium 0.15 mg kg^-1. The patients were randomly assigned to one of four study groups. The control group received nitrous oxide in oxygen (2: 1) supplemented with fentanyl, while in the other groups halothane was administered at different end-tidal concentrations: 0.19% (Group 2), 0.37% (Group 3), 0.74% (Group 4), corresponding to 0.25, 0.5 and 1.0 MAC of halothane. Neuromuscular block was kept at 95% with a closed-loop feedback infusion of mivacurium and monitored with electromyography. Plasma cholinesterase concentrations and dibucaine numbers were determined. Results: Mivacurium infusion requirements (mean±SD) were 7.5±3.1 μg kg^-1 min^-1 with nitrous oxide-fentanyl anaesthesia. In the groups receiving 0.25, 0.5 or 1.0 MAC of halothane the steady-state infusion rates of mivacurium were reduced to 6.3±2.8, 5.6±1.4 and 5.7±2.5 μg-kg^-1min^-1 (P < 0.05), respectively. There was a linear relationship between mivacurium infusion requirements and plasma cholinesterase activity. Conclusion: Halothane anaesthesia reduces mivacurium infusion requirements by 15–25% compared to nitrous oxide-fentanyl anaesthesia. Interindividual differences in the extent of this interaction are great.