Intramuscular rapacuronium in infants and children: dose-ranging and tracheal intubating conditions.

BACKGROUND: Intravenous rapacuronium's rapid onset and short duration suggest that intramuscular rapacuronium might facilitate tracheal intubation without prolonged paralysis. Accordingly, the authors injected rapacuronium into the deltoid muscle to determine the optimal dose and time for intubation in pediatric patients. METHODS: Unpremedicated patients (aged, 2 months to 3 yr) were studied. Part I: Spontaneous minute ventilation (V(E)) and twitch tension were measured during N2O/halothane anesthesia. Rapacuronium (2.2-5.5 mg/kg, given intramuscularly, n = 23), succinylcholine (4 mg/kg, given intramuscularly, n = 12), or vecuronium (0.1 mg/kg, given intravenously, n = 15) was given. Time to 50% depression of V(E) and 10% recovery of twitch were measured. Dose for each patient was changed 10-20% according to the previous patient's response. Part II: In 22 patients anesthetized with 0.82-1.0% halothane, the optimal rapacuronium dose determined in part I (infants, 2.8 mg/kg; children, 4.8 mg/kg) was given intramuscularly. Laryngoscopy was scored. Time to laryngoscopy was increased or decreased 0.5 min according to the previous patient's response. RESULTS: Part I: Rapacuronium typically depressed ventilation in < or = 2 min with 10% twitch recovery in 20-60 min. With succinylcholine, median time to ventilatory depression was 1.3 and 1.1 min for infants and children, respectively; for vecuronium, 0.7 and 0.6 min. Part I: Intubating conditions were good-excellent at 3.0 and 2.5 min in infants and children, respectively; time to 10% twitch recovery (mean +/- SD) was 31 +/- 14 and 36 +/- 14 min in the two groups. CONCLUSIONS: This pilot study indicates that deltoid injection of rapacuronium, 2.8 mg/kg in infants and 4.8 mg/kg in children, permits tracheal intubation within 2.5-3.0 min, despite a light plane of anesthesia. Duration of action is intermediate.     

Intramuscular rapacuronium in infants and children: a comparative multicenter study to confirm the efficacy and safety of the age-related tracheal intubating doses of intramuscular rapacuronium (ORG 9487) in two groups of pediatric subjects

BACKGROUND: This multicenter, assessor, blinded, randomized study was conducted to confirm and extend a pilot study in which intramuscular rapacuronium was given to infants and children to confirm efficacy and to evaluate tracheal intubating conditions. METHODS: Ninety-six pediatric patients were studied in two groups: infants aged 1 to 12 months (n = 46) and children aged 1 to 3 yr (n = 50). Infants received 2.8 mg/kg and children 4.8 mg/kg of intramuscular rapacuronium during 1 minimum alveolar concentration halothane anesthesia. These two groups were studied in three subgroups, depending on the time (1.5, 3, or 4 min) at which tracheal intubation was attempted after the administration of intramuscular rapacuronium into the deltoid muscle. Neuromuscular data collected included onset time, duration of action, and recovery data during train-of-four stimulation at 0.1 Hz. Data were analyzed by the Cochran-Mantel-Haenszel procedure. RESULTS: The tracheal intubating conditions were deemed acceptable in 17, 36, and 64% of infants and 20, 47, and 71% of children at 1.5, 3, or 4 min, respectively. The mean values for % of control twitch height (T1) 2 min after rapacuronium in both groups were similar. The mean (SD) time required to achieve more than or equal to 95% twitch depression in infants was 6.0 (3.7) versus 5.5 (3.8) min in children. CONCLUSIONS: Only 27% of patients achieved clinically acceptable tracheal intubating conditions at 1.5 or 3 min after administration of 2.8 mg/kg and 4.8 mg/kg rapacuronium during 1 minimum alveolar concentration halothane anesthesia. Tracheal intubation conditions at 4 min were acceptable in 69% of subjects. The duration of action of 4.8 mg/kg of rapacuronium in children was longer than 2.8 mg/kg of rapacuronium in infants.     

Comparison of different priming techniques on the onset time and intubating conditions of rocuronium

BACKGROUND AND OBJECTIVE: The aim was to compare the effects of two different priming doses and priming intervals with the standard intubating dose of rocuronium on the onset time and intubation conditions. METHODS: After induction of anaesthesia, 75 patients were randomly assigned to one of five groups. Patients in Group 1 received a priming dose of rocuronium 0.06 mg kg(-1) followed 2 min later by rocuronium 0.54 mg kg(-1), Group 2 received a priming dose of 0.10 mg kg(-1) followed 2 min later by a rocuronium injection of 0.50 mg kg(-1). Group 3 was given a priming dose of 0.06 mg kg(-1) followed 3 min later by administration 0.54 mg kg(-1), where Group 4 received a priming dose of 0.10 mg kg(-1) followed 3 min later by injection of 0.50 mg kg(-1). Group 5 received a placebo injection followed 3 min later by rocuronium 0.60 mg kg(-1). RESULTS: Priming with a 3 min priming interval shortened the onset time of rocuronium irrespective of the dosage of (P < 0.001). Clinical duration of action was significantly longer after priming in Group 4 than in Group 5. Clinically acceptable intubation conditions were obtained in all patients. CONCLUSIONS: Priming with a 3 min priming interval was effective when rapid tracheal intubation with rocuronium was necessary. However, priming with rocuronium should be used carefully with special attention given to the possibility of hypoxia and aspiration of gastric contents in awake patients.     

Low doses of rocuronium during remifentanil-propofol-based anesthesia in children: comparison of intubating conditions

BACKGROUND : In this prospective double-blind study, intubation conditions were compared at 90 s following two different low doses of rocuronium during remifentanil and propofol anesthesia in children undergoing ambulatory procedures. METHODS : Forty-four children (ASA I-II, aged 3-12 years) undergoing day case ENT surgery were premedicated with midazolam 0.5 mg x kg(-1). Following atropine 10 microg x kg(-1), remifentanil infusion 0.5 microg x kg(-1) x min(-1) was started. After 60 s, anesthesia was induced with propofol 2.5 mg x kg(-1). Immediately after a bolus dose of propofol, the children received rocuronium doses of 0.15 mg x kg(-1) (group I, n = 22) or 0.3 mg x kg(-1) (group II, n = 22) in a randomized manner, after which an infusion of propofol 6 mg x kg(-1) h(-1) was added to the infusion of remifentanil 0.5 microg x kg(-1) min(-1) for maintenance of anesthesia. Intubating conditions were evaluated 90 s after rocuronium administration applying the Copenhagen Scoring System which included components of laryngoscopy, vocal cord movement and reaction to intubation. Hemodynamic values were recorded at predetermined time intervals. RESULTS : Excellent, good and poor intubation conditions were 18.2, 40.9 and 40.9% in group I and 40.9, 54.5 and 4.5% in group II. Clinically acceptable intubating conditions (excellent and good) were significantly higher in group II (95.5%) than in group I (59.1%) (P = 0.004). Mean values of heart rate and blood pressure did not differ significantly between groups. No children required any intervention for hemodynamic instability and/or muscle rigidity. CONCLUSIONS : The results suggest that 0.3 mg x kg(-1) of rocuronium may be a better low dose than 0.15 mg x kg(-1) of rocuronium for clinically acceptable intubating conditions in pediatric ambulatory surgery during remifentanil-propofol-based anesthesia at the doses used in the study.     

The onset of neuromuscular block at the masseter muscle as a predictor of optimal intubating conditions with rocuronium.

After an intubating dose of rocuronium satisfactory intubating conditions are achieved before the onset time at the adductor pollicis. We examined the possibility that measurement of the relaxation of the masseter muscle is a more appropriate guide when determining the intubating time. Simultaneous accelerometry with a 0.1-Hz single twitch stimulation of the chin and thumb was performed in 20 patients after 0.6 mg kg-1 rocuronium. We observed a significantly more brief mean lag time and onset time at the masseter muscle (22.5 and 61 vs. 32.5 and 160 s). The corresponding mean relaxation at the onset time was also significantly more pronounced at the masseter muscle (99.6 vs. 97.6%). A mean onset time at the masseter muscle of 61 s as produced by rocuronium corresponds clinically with excellent or good intubating conditions. From these results, we suggest that measurement of the onset time of muscle relaxation at the masseter muscle appears to be a better predictor of good intubating conditions than measurements made using the adductor pollicis muscle after administration of rocuronium.     

The effect of ephedrine on intubating conditions and haemodynamics during rapid tracheal intubation using propofol and rocuronium

Background: We compared the effect of pre-treatment with ephedrine 75, 100,150 µg kg^–1 and saline on intubating conditionsand haemodynamics during rapid tracheal intubation using propofoland rocuronium. Methods: One hundred adult patients randomized into one of the four groups—PE75, PE 100, PE 150, and saline (control) groups—were pre-treatedwith i.v. ephedrine 75, 100, 150 µg kg^–1 or saline,respectively, 1 min before rapid tracheal intubation using propofol2.5 mg kg^–1 and rocuronium 0.6 mg kg^–1. A blindedanaesthesiologist assessed the intubating conditions. Heartrate and mean arterial pressure were recorded before anaesthesiainduction (baseline), post-induction, and every minute afterintubation for 5 min. A 20% change in haemodynamic variablesfrom baseline was regarded as clinically significant. Data wereanalysed using ANOVA test with post hoc Tukey's test and ² orFisher's exact test. P < 0.05 was regarded as significant. Results: Patient characteristics, baseline heart rate, and mean arterialpressure were comparable between the groups. Intubating conditionswere significantly better in the PE 75 (P = 0.003) and PE 100(P = 0.001) groups. A significant increase in heart rate wasobserved in the PE 75 and PE 150 groups when compared with thesaline group. A statistically significant difference in meanarterial pressure was noted between PE 75 and PE 150 groupsand between PE 150 and saline groups at most of the time intervals.However, when considering the clinical significance of these,all groups were comparable (P > 0.05). Conclusions: Ephedrine either 75 or 100 µg kg^–1 given beforerapid tracheal intubation using propofol and rocuronium bromideimproves the intubation conditions. It is not effective in preventingthe hypotension which follows ensuing induction of anaesthesia.     

Onset/offset characteristics and intubating conditions of rapacuronium: a comparison with rocuronium

We compared onset and offset of action and tracheal intubatingconditions after rapacuronium and rocuronium in 60 patientsin a randomized, assessor-blinded study. Following inductionof anaesthesia with propofol 2.5 mg kg^–1, eitherrapacuronium 1.5 mg kg^–1 (n=30) or rocuronium0.6 mg kg^–1 (n=30) was administered to facilitatetracheal intubation. Anaesthesia was maintained with eithera propofol infusion (100 µg kg^–1 min^–1)or sevoflurane (1% end-tidal) with 66% nitrous oxide (N₂O),n=15 in each subgroup. Neuromuscular monitoring was performedusing an electromyographic (EMG) device (Datex Relaxograph).The lag times (mean 42 (SD 11) s and 44 (16) s), maximumblock (99 (2)% and 98 (3)%) and intubating conditions at 60 s(good-to-excellent in 86% and 84% of patients) were similarfor rapacuronium and rocuronium, respectively. The onset timeof rapacuronium was shorter than rocuronium (87 (20) vs 141(65) s, P<0.001), and the degree of block at 60 swas greater (69 (26) vs 50 (27)%, P<0.05). Twenty-five percent recovery was shorter with rapacuronium than rocuroniumduring propofol (15.0 (3.2) vs 39.1 (14.2) min, P<0.001)and sevoflurane (15.1 (4.2) vs 47.8 (19.0) min, P<0.001)anaesthesia. We conclude that rapacuronium 1.5 mg kg^–1had a more rapid onset, similar intubating conditions, and shorterrecovery times than rocuronium 0.6 mg kg^–1. Br J Anaesth 2000; 85: 246–50     

Atracurium in clinical anaesthesia: effect of dosage on onset, duration and conditions for tracheal intubation

Conditions for tracheal intubation at 90 seconds, time to onset of maximum block and duration of clinical relaxation after five different doses of atracurium, which ranged from 0.4 to 1.0 mg/kg were studied in 200 adult patients who were anaesthetized with nitrous oxide, oxygen and halothane or fentanyl. The conditions for intubation improved significantly with increasing doses, and were acceptable in 55% patients with a 0.4 mg/kg dose and in about 90% of those who received the two higher doses. The time to onset of complete block was 257 seconds with 0.4 mg/kg and decreased progressively to 124 seconds with 1.0 mg/kg. The duration of clinical relaxation under fentanyl anaesthesia averaged 29 minutes with 0.4 mg/kg and increased in a dose-related manner to 57 minutes with 1.0 mg/kg: halothane anaesthesia produced only a marginal increase. There was no evidence of cumulation with up to six repeat doses of 0.125 mg/kg. The only side effect noticed was cutaneous flushing observed in 42% of patients. This was again dose dependent, being 18% with 0.4 mg/kg and increasing to 73% after 1.0 mg/kg. There was associated hypotension and bronchospasm in one patient.     

Onset of neuromuscular blockade and intubating conditions one minute after the administration of rocuronium in children

In a blinded randomized study intubating conditions were compared at one min following intravenous induction with propofol and either suxamethonium 1.0 mg·kg⁻¹, or rocuronium 0.6 mg·kg⁻¹. Onset time to maximal twitch depression, % block at one minute and clinical duration (time to 25% recovery) were measured. Sixty children undergoing elective tonsillectomy were recruited. Onset time [42 s ( SD 11 s)] and clinical duration [3.3 min ( SD 1.0 min)] in the suxamethonium group was significantly ( P <0.001) less than in the rocuronium group [92 s (41 s)] and [24.2 min (6.6 min)] respectively. The median twitch height at one minute for suxamethonium was 0% (range 0–8%) and significantly greater ( P <0.001) at 5% (range 0–22%) for rocuronium. Despite this there was no difference in the intubating conditions at one minute with 25 excellent/5 good in the suxamethonium group and 27 excellent/3 good in the rocuronium group. We conclude that rocuronium 0.6 mg·kg⁻¹ gives optimal intubating conditions at one minute in children.     

Assessment of tracheal intubating conditions in children using remifentanil and propofol without muscle relaxant

BACKGROUND: Tracheal intubation in children can be achieved by deep inhalational anaesthesia or an intravenous anaesthetic and a muscle relaxant, suxamethonium being widely used despite several side-effects. Studies have shown that oral intubation can be facilitated safely and effectively in children after induction of anaesthesia with propofol and alfentanil without a muscle relaxant. Remifentanil is a new, ultra-short acting, selective mu-receptor agonist that is 20-30 times more potent than alfentanil. This clinical study was designed to assess whether combination of propofol and remifentanil could be used without a muscle relaxant to facilitate tracheal intubation in children. METHODS: Forty children (5-10 years) admitted for adenotonsillectomy were randomly allocated to one of two groups to receive remifentanil 2 microg.kg(-1) (Gp I) or remifentanil 3 microg.kg(-1) (Gp II) before the induction of anaesthesia with i.v. propofol 3 mg.kg(-1). No neuromuscular blocking agent was administered. Intubating conditions were assessed using a four-point scoring system based on ease of laryngoscopy, jaw relaxation, position of vocal cords, degree of coughing and limb movement. Mean arterial pressure (MAP) and heart rate (HR) measured noninvasively before induction of anaesthesia to 5 min after intubation (seven time points). RESULTS: Tracheal intubation was successful in all patients without requiring neuromuscular blocking agent. Intubating conditions were clinically acceptable in 10 of 20 patients (50%) in Gp I compared with 18 of 20 patients (90%) in Gp II (P < 0.05). MAP and HR decreased in both groups after induction of anaesthesia (P < 0.01). Both HR and MAP were significantly lower in Gp II compared with Gp I after tracheal intubation (P < 0.01). No patient in the present study developed bradycardia or hypotension. CONCLUSIONS: We conclude that remifentanil (3 microg.kg(-1)), administered before propofol (3 mg.kg(-1)) provides acceptable tracheal intubating conditions in children, and completely inhibited the increase in HR and MAP associated with intubation.     

Onset and duration of action of rocuronium in children receiving chronic anticonvulsant therapy

The onset and time course of action of rocuronium in normal children and children receiving anticonvulsant drugs for prolonged periods was characterized. A single bolus dose of 0.6 mg.kg-1 rocuronium was administered i.v. to seven nonepileptic patients on no medication, and eight patients on chronic anticonvulsant therapy consisting of either phenytoin, carbamazepine, or both who were age and weight matched. Neuromuscular transmission was monitored by the evoked compound electromyography of the thenar muscles using train of four stimulation every 20 s. Recovery times of the first twitch to 10%, 25%, 50%, 75% and 100% of baseline values and recovery index were obtained. The onset times were 1.05+/-0.5 and 1.41+/-0.5 min for the control and anticonvulsant groups respectively and were not significantly different. Children receiving chronic anticonvulsant therapy had significantly shorter recovery index than the control group (control 10.4+/-5.1 min, anticonvulsant 4.8+/-1.7 min, P<0.05). Furthermore, the duration of recovery to 10%, 50%, 75% and 100% of baseline T1 values was less in the anticonvulsant drug group. Our data confirm resistance to rocuronium in children on chronic anticonvulsant drugs.     

The effect of desflurane on rocuronium onset, clinical duration and maintenance requirements

Volatile anesthetics potentiate the effects of non-depolarizing agents. This study investigated the interaction between the inhalational anesthetic desflurane and rocuronium. Forty ASA I and II patients randomly received desflurane/N2O/fentanyl, or propofol/ N2O/fentanyl anesthesia, and rocuronium 0.6 mg/kg. Neuromuscular block was assessed at the adductor pollicis muscle. Block onset and clinical duration times were measured; a rocuronium infusion was started when the first twitch on train-of-four returned to 10% of control (T10%). Maintenance infusion requirements and recovery profiles (spontaneous and after reversal) were recorded until recovery of twitch to 90% of control (T90%). Rocuronium onset was prolonged by 67% (p = 0.034), clinical duration by 30% (p = NS), and infusion requirements were lower in the desflurane group (4.5 vs. 7.1 mg/kg/min, p = 0.003). Recovery times were not statistically different. Desflurane significantly delays the onset of neuromuscular block, potentiates rocuronium during maintenance infusion, but does not affect clinical duration or recovery.     

The effect of ketamine on tracheal intubating conditions without neuromuscular blockade during sevoflurane induction in children

Purpose  

The purpose of this study was to investigate the effect of ketamine on intubating conditions for tracheal intubation during anesthesia induction with sevoflurane and alfentanil in pediatric patients.     

Rapid tracheal intubation with rocuronium: a probability approach to determining dose.

BACKGROUND: Rapid tracheal intubation with rocuronium has not been studied using a probability-based approach. The authors aimed to predict doses of rocuronium giving 90% and 95% probability of in intubation within 60 s and to estimate their durations of action. METHODS: After premedication with midazolam, 2 mg, anesthesia was induced in 80 subjects with fentanyl, 2 microg/kg, followed 3 min later by propofol, 2 mg/kg. Patients received randomly rocuronium, 0.0, 0.4, 0.8, or 1.2 mg/kg (n = 20/ dose). Laryngoscopy began 40 s later, aiming for intubation at 60 s, and conditions were graded perfect, acceptable, or unacceptable, with the first two conditions being successful intubation. Anesthesia was maintained with isoflurane 0.5-1.0% (end-tidal) and fentanyL Duration of action was time until reappearance of the first tactile train-of-four response. The dose versus fraction of patients with successful intubation was analyzed by logistic regression. Doses giving 90% and 95% (D90 and D95) probability of successful intubation were calculated. RESULTS: intubation was successful in 7, 11, 18, and 19 patients in the 0.0, 0.4, 0.8, and 1.2 mg/kg groups, respectively. The D90 and D95 doses (95% confidence limits in parentheses) were 0.83 (0.59-1.03) and 1.04 (0.76-1.36) mg/kg, respectively. Estimated time until first tactile train-of-four response after D90 and D95 doses was 32 and 46 min, respectively. CONCLUSIONS: After induction with fentanyl and propofol, rocuronium, 1.04 mg/kg gives 95% probability of successful intubation at 60 s.     

Tracheal intubating conditions and pharmacodynamics following cisatracurium in infants and children undergoing halothane and thiopental-fentanyl anesthesia

BACKGROUND: The aims of the present study were to determine the tracheal intubating conditions, onset time, duration of action, and hemodynamic responses following the administration of cisatracurium 0.15 mg x kg(-1) to infants and children. METHODS: One hundred and eighty-one infants and children aged 1 month to 12 years were randomized to two groups to receive anesthesia with nitrous oxide-oxygen-halothane (group H) or nitrous oxide-oxygen-thiopental-fentanyl (group TF). Intubation conditions were assessed 120 s after cisatracurium administration using a 4-part scale. Neuromuscular transmission was monitored by recording the evoked compound electromyogram of the adductor pollicis. RESULTS: The proportion of patients with excellent or good intubating conditions was similar in both groups (88 of 90, 98% in group H; 85 of 90, 94% in group TF). However, there was a significantly greater proportion of excellent intubating conditions in group H (79 of 90, 88%) compared with group TF (65 of 90, 72%) (P = 0.01) and recovery time was significantly longer in group H compared with group TF (P < 0.001). There was also a higher proportion of excellent intubating conditions in infants compared with older subjects (P = 0.02) and a shorter onset time (P < 0.001) and longer recovery time (P < 0.001) in younger compared with older patients. Changes in heart rate and arterial pressure were negligible 1 min following the cisatracurium administration. CONCLUSIONS: Cisatracurium 0.15 mg x kg(-1) produces acceptable intubating conditions at 120 s in the great majority of infants and children. Anesthesia background and age have significant effects on intubating conditions and duration of action of cisatracurium.     

Evaluation of the endotracheal intubating conditions of rocuronium (ORG 9426) and succinylcholine in outpatient surgery.

The time-course of action and tracheal intubating conditions of rocuronium and succinylcholine under intravenous anesthesia with propofol, alfentanil, and nitrous oxide were studied in 30 patients undergoing outpatient surgery. The neuromuscular effects of both drugs were quantified by recording the indirectly evoked twitch response of the adductor pollicis muscle after ulnar nerve stimulation (0.1 Hz, 0.2 ms supramaximal stimuli). Patients were given either 0.6 mg/kg rocuronium (n = 20) or 1 mg/kg succinylcholine (n = 10) intravenously. Sixty seconds after the administration of the muscle relaxant, the trachea was intubated and the intubating conditions were scored by a "blinded" assessor. Intubating conditions were not different (P = 0.34) between the rocuronium and succinylcholine groups. The onset and duration of neuromuscular blockade were shorter with succinylcholine than with rocuronium. The depression of the twitch response to 5% of control value occurred in 0.8 +/- 0.1 min with 1 mg/kg succinylcholine and 1.2 +/- 0.5 min with 0.6 mg/kg rocuronium (P less than 0.01). The recovery of the twitch response to 25%, 75%, and 90% of its control value was shorter after succinylcholine (P less than 0.001) and occurred at 8.1 +/- 2.6, 10.3 +/- 3.9, 11.3 +/- 4.6 and 25.3 +/- 5.0, 33.1 +/- 5.9, 36.1 +/- 6.3 min after succinylcholine and rocuronium, respectively. Also the time required for spontaneous recovery from 25% to 75% of the control twitch response was significantly shorter (P less than 0.001) after succinylcholine (2.2 +/- 1.4 min) than after rocuronium (7.8 +/- 2.1 min). It is concluded that in spite of the pharmacodynamic differences between succinylcholine and rocuronium, the intubating conditions after administration of both compounds are similar and develop at the same rate.     

Comparison of rocuronium and suxamethonium for rapid tracheal intubation in children

BACKGROUND: The purpose of our study was to determine whether a smaller dose of rocuronium than previously reported could provide similar intubating conditions to suxamethonium during rapid-sequence induction of anaesthesia in children. METHODS: One hundred and twenty ASA I, unpremedicated children, aged 1-10 years, who were undergoing elective surgery, were randomized into three groups to receive rocuronium 0.6 mg.kg-1, rocuronium 0.9 mg.kg-1 or suxamethonium 1.5 mg.kg-1. The study was double-blinded, anaesthesia and timing of injection was standardized to alfentanil 10 microg.kg-1, thiopentone 5 mg.kg-1 and the study drug. Intubation was attempted at 30 s after injection of neuromuscular relaxant and intubating conditions graded as excellent, good, poor or impossible. RESULTS: All 120 children were successfully intubated within 60 s without need for a second attempt after administration of neuromuscular relaxant. Differences between suxamethonium and rocuronium 0.6 mg.kg-1 and between the two doses of rocuronium were statistically significant (P=0.016 and 0.007, respectively). CONCLUSIONS: Rocuronium 0.9 mg.kg-1 provides similar intubating conditions to suxamethonium 1.5 mg.kg-1 during modified rapid-sequence induction using alfentanil and thiopentone in children (P=0.671). Rocuronium 0.6 mg.kg-1 was inadequate.