A Prospective Randomized Control Trial to Study Effect of Priming Principle on the Induction Dose Requirements of Propofol.

Introduction: Priming refers to administration of asubanaesthetic dose (priming dose) of an agent prior to itsactual anaesthetic dose. The “priming principle” is a methodto reduce the total dose requirements of a drug. This studywas undertaken to study the effect of priming principle oninduction dose requirements of propofol.Material and Methods: Sixty (60) patients with AmericanSociety of Anaesthesiologists (ASA) I and ASA II grades,of both sexes, aged 18-55 years, and undergoing electivesurgical procedures under general anaesthesia were randomlyallocated into two equal groups with 30 patients each. GroupI (control) received calculated induction dose of injection(inj.) propofol 2mg/kg. Group II (study) received 20% of totalcalculated induction dose of propofol 2 mg/kg as a primingdose and remaining dose after 60 seconds titrated till loss ofthe eyelash reflex.Results: The control group consumed a higher dose of inj.propofol (2 mg/kg) as compared with the study group (1.34± 0.28 mg/kg), i.e., there was 33% reduction of the total dosein the study group. The hemodynamic changes in HR, SBP,DBP, MAP and RPP at 30 minutes before induction, justbefore induction, immediately after intubation and 5 minutesafter induction were similar in both groups (P > 0.05) .Thehemodynamic changes in HR, SBP, DBP, MAP and RPP atone minute after induction were statistically significant inboth the groups (P< 0.05). Incidence of pain and apnea wascomparable in both groups but hypotension was seen in 4patients in control group and none in study group.Conclusion: The priming technique effectively reduced thetotal induction dose requirements of propofol and favourablyreduced extent of hypotension following induction withpropofol.

The effect of priming with rocuronium on onset time and intubation conditions during endotracheal intubation with low-dose rocuronium / 대한마취과학회지

BACKGROUND: A priming dose of rocuronium can shorten the onset time of neuromuscular blockade. The purpose of this study was to evaluate the effect of priming with rocuronium on the onset time and intubation conditions during tracheal intubation with low-dose rocuronium (0.35 mg/kg) and to compare results with those for rocuronium 0.45 mg/kg. METHODS: One hundred twenty four patients were randomly allocated to three groups. Following induction of anesthesia, groups I and III received normal saline while group II received a priming dose of rocuronium (0.05 mg/kg). Three minutes after priming, groups I, II and III received, respectively, 0.45 mg/kg, 0.3 mg/kg and 0.35 mg/kg rocuronium. Intubation was performed 2 minutes after the administration of an intubating dose and intubation conditions were evaluated. Neuromuscular blockade was assessed by accelerography. RESULTS: The proportion of cases having optimal intubation conditions in group I was higher than in groups II and III. There was no significant difference in the onset times among groups. Neuromuscular blockade at 60, 90 and 120 seconds after an intubating dose was similar among all groups except at 60 sec. Maximal blockade for group I was deep compared to groups II and III. CONCLUSIONS: Rocuronium 0.35 mg/kg does not provide satisfactory intubation conditions. There are no effects on onset time and intubation conditions due to priming during tracheal intubation with rocuronium 0.35 mg/kg.

Rapid-Sequence Intubation with Rocuronium / 대한마취과학회지

BACKGROUND: Succinylcholine is still the most frequently used muscle relaxant for rapid-sequence intubation despite its well-known side effects. Rocuronium has been reported to develop a rapid onset of action and may be suitable as a component of a rapid-sequence intubation. The purpose of this study was to compare tracheal intubating conditions by following different rocuronium doses and application techniques versus succinylcholine. METHODS: Fifty nine ASA physical status 1 and 2 adult patients scheduled for elective surgeries were anesthetized with thiopental sodium 5 mg/kg and muscle relaxant using a rapid-sequence technique. Group I (n = 12) received succinylcholine 1.0 mg/kg, group II (n = 15) received rocuronium 1.0 mg/kg, group III (n = 16) received rocuronium 0.6 mg/kg as a single bolus dose, and group IV (n = 16) received a priming dose of rocuronium 0.06 mg/kg followed three minutes later by rocuronium 0.54 mg/kg. Intubation was performed 60 seconds after the administration of muscle relaxant and intubating conditions were evaluated by clinical scoring (Table 1), and train-of-four (TOF) count of the adductor pollicis by accelerography. RESULTS: TOF counts of group I were lower than those of groups III and IV, and those of group II were lower than group III (P < 0.0083). Group II had intubating conditions similar to group I. The intubating conditions of groups I and II were better than those of groups III and IV (P < 0.0083). CONCLUSIONS: Rocuronium 1.0 mg/kg may be a suitable alternative for succinylcholine 1.0 mg/kg during rapid-sequence intubation. Priming principle does not produce faster or better intubating conditions than a single bolus injection.

The Study of Priming with Vecuronium and Atracurium on Young and Elderly Patients / 대한마취과학회지

BACKGROUND: Succinylcholine is the muscle relaxant of choice for rapid endotracheal intubation, but may produce many side effects such as hyperkalemia, myalgia, increase intraocular pressure. Nondepolarizing muscle relaxants were used instead of succinylcholine, still late onset time was be dangerous. For this reason, priming principle was reported and applied to rapid intubation using nondepolarizing muscle relaxation. We studied the effect of priming with vecuronium and atracurium on elderly and young patients. METHODS: We were randomly assigned 40 patients and observed the effects of priming doses of vecuronium (0.01 mg/kg) and atracurium (0.05 mg/kg). Ten young (20-35 yrs) and ten elderly (65-75 yrs) patients were each placed in vecuronium and atracurium group. Arterial blood gas analysis and train of four (TOF) were determined before priming. All tests were performed again 4 min after vecuronium and 3 min after atracurium. We asked for symptoms and signs of muscle weakness. RESULTS: In arterial blood gas analysis and TOF ratio were decreased in both groups. There is no significant difference between two groups in all tests. PaO2 and TOF ratio were reduced more in elderly patients, significantly (P<0.05). Symptoms and signs of muscle weakness such as ptosis, dizziness, diplopia, swallowing difficulty and respiratory difficulty in elderly patients were more frequent than in young patients. CONCLUSIONS: Priming doses of vecuronium and atracurium produced greater decrease in muscle strength, PaO2 and TOF ratio in the elderly than in their younger counterparts. So using priming method in elderly patients, we need adequate pre-oxygenation and thorough monitoring before endotracheal intubation.

Effects of priming with pancuronium or rocuronium on intubation with rocuronium in children

Rocuronium is a non-depolarizing neuromuscular blocking agent which has a rapid onset and intermediate duration of action. The goal of this study was to compare the neuromuscular blocking actions of rocuronium with and without a priming dose of pancuronium or rocuronium in children. Thirty patients were randomly allocated into 3 groups. Ten patients received a single dose of 0.6 mg/kg rocuronium (Group I). The others received either 0.015 mg/kg pancuronium (Group II) or 0.06 mg/kg rocuronium (Group III) 3 minutes before an intubating dose of 0.54 mg/kg rocuronium was given. Neuromuscular blockade was measured via accelerographic response to single stimulations (1 Hz) of the ulnar nerve until maximal twitch depression was reached followed by train-of-four (TOF) stimuli (2 Hz) at 15 second intervals for the remainder of recovery. Groups were compared with regard to onset time, duration and recovery indices. The onset time and duration of block did not differ significantly between groups. However, the time to recovery in group II (24.5 +/- 9.9 min) was significantly prolonged compared to that in group I (12.7 +/- 3.1 min) or group III (12.7 +/- 3.9 min). We concluded that the use of rocuronium with a preceding dose of either pancuronium or rocuronium provided no advantage for intubation in children.

Vecuronium or Pancuronium as a Priming Agent is Effective to Shorten the Onset of Mivacurium-Induced Neuromuscular Block for Endotracheal Intubation / 대한마취과학회지

BACKGROUND: Mivacurium is a non-depolarizing neuromuscular blocking agent which has short duration of action. The goal of this study was to describe a technique which could shorten the onset time of mivacurium for rapid endotracheal intubation by using priming principle. METHODS: Thirty-one patients were randomly allocated into four groups. Patients in group I(n=8) received a single dose of 0.12 mg/kg mivacurium. Those in group II(n=10), III(n=6), and IV(n=7) received 0.015 mg/kg pancuronium, 0.012 mg/kg vecuronium, and 0.008 mg/kg mivacurium 4 minutes before the intubating dose of 0.12 mg/kg mivacurium was given respectively. Accelerographic response to train-of-four(TOF) stimulation of ulnar nerve at 15 seconds interval was used for neuromuscular monitoring. The onset time, the duration and recovery indices were compared between groups. RESULTS: The onset time in group II (2.9 0.49 min) and III (2.33 0.4 min) were significantly faster than that in group I (5.19 0.47 min). In the group II, the duration (26.3 1.9 min) and recovery index (12.35 2.45 min) were significantly prolonged than those in group I (9.12 1.21 and 4.75 0.52 min), respectively. CONCLUSION: The onset time is more rapid when pancuronium or vecuronium is used as priming agent than when mivacurium as single bolus injection or priming agent.

Comparison of Onset Time of Mivacurium by Priming Principle with Succinylcholine during Endotracheal Intubation / 대한마취과학회지

BACKGROUND: Mivacurium has a characteristics of rapid onset and the shortest duration of non- depolarizing neuromuscular relaxants and the onset of action could be accelerate more rapidly by using priming principle. The purpose of this study was to compare the onset time of mivacurium by priming principle with succinylcholine during rapid endotracheal intubation. METHODS: 36 patients were randomly divided into 3 groups: mivacurium group by priming principle (Group 1), mivacurium group by bolus injection (Group 2) and succinylcholine group (Group 3). In Group 1, subparalyzing dose of 0.02 mg/kg was administered 2 minutes before principle dose of 0.25 mg/kg was given. Onset time and intubating conditions were observed when twitch tension was reduced by 25% block in each group. RESULTS: The onset of Group 1 (75 sec) was significantly faster than that of Group 2 (90 sec) (p<0.05) but was significantly slower than that of Group 3 (37.5 sec) (p<0.05). Intubating conditions were excellent in all groups. CONCLUSIONS: The attempts of priming principle with mivacurium could accelerate the onset of action of mivacurium compared with that of bolus injection but their onsets were shorter than those produced by succinylcholine.

Comparion of Single Bolus with Divided Doses of Rocuronlum for Tracheal intubation / 대한마취과학회지

BACKGROUND: Onset of rocuronium is rapid but relatively large doses are needed to achieve a suitable intubating condition. So we compared the single bolus injection with divided injection of rocuronium about tlie onset time, intubation time and intubating condition. METHOD: Thirty patients were divided into three groups of 10 each randomly. Patients in group I were given a single dose of 0.6mg/kg rocuronium. Those in group 2I or 3 received 0.06 mg/kg or 0.09 mg/kg as priming dose followed by 0.54 mg/kg and 0.81 mg/kg as intubating dose 3 min. later. The train of four responses of adductor pollicis muscle was recorded using Paragraph(Utah Medical Product Inc. Midvale Utah, U.S.A.) every 10 seconds. The trachea was intubated by one clinician who was blinded to the muscle relaxant administered when he thought the patients were suitable for intubation, and he recorded the intubating conditions. The endotracheal intubation time and twitch height at the moment was recorded by other clinician. The onset time was recorded when the post tetanic count is marked as '0'. RESULT: The onset time of group 1, 2, and 3 were 90.0+/-22.lsec, 109.0+/-35.0 sec and 85.0+/-35.0 sec. respectively. Endotracheal intubation times were 77.0+/-10.6sec, 60.0+/-10.0sec and 44.0+/-5.2sec respectively. CONCLUSION: There was no differences about onset time between single and devided injection with same total dose or incremental dose of 0.9mg/kg. But the intubation time was faster in priming group with dose dependent manner, and the intubating conditions were excellent to good in all patients.

Comparison of d-tubocurarine with vecuronium as the priming drug for vecuronium induced neuromuscular blockade / 대한마취과학회지

Administration of a subparalytic dose of a nondepolarizing muscle relaxant prior to intubating dose hastens the onset time of neuromuscular blockade. This study was designed to investigate the influence of a priming dose of vecuronium (0.015 mg/kg) and d-tubocurarine (0.05 mg/kg) on intubating dose of vecuronium (0.085 mg/kg). The authors measured TOF ratio using neuromuscular monitoring. This monitoring was carried out by stimulation of ulnar nerve at a frequency of 2Hz every 20 seconds using Datex relaxograph to measure the compound evoked electrographic response of hypothenar muscle. The patients were randomly divided into two groups as priming dose ; vecuronium and dtubocurarine (DTC) group respectively. Mixture of two different nondepolarizing muscle relaxant may produce synergism, although the reason for this synergism is unknown. It may be the results of the action of the drugs at different sites. In our study, we found the results as follows ;1) The rapid onset was occured with d-tubocurarine(0.05 mg/kg) as priming drug than vecuronium (0.015 mg/kg) 2) The duration was longer when d-tubocurarine was used (P<0.05) The authors conclude that the onset is more rapid and the duration is longer when other species of nondepolarizing muscle relaxant is used than same agent is used as priming drug.

The Priming Principle with Anticholinesterases for the Recovery of Profound Muscle Relaxation / 대한마취과학회지

The success of accelerating the onset of neuromvacular blocking drugs by giving them in divided doses encouraged others to attempt the same "priming principle" using reversal agents. Naguib et al and Abdulatif et al demonstrated that the reversal time(time to reach a TOF of 0.75) was reduced when the reversal agent was administered in divided doses at T, 10% of control. But Donati et al and Szalados et al either could not detect any differences in the rate of reversal when anticholinestereses were administered in divided doses. This study hes been conducted to evaluate the reversal effects of neostigmine or pyridostigmine with priming principle in the rabbit after pancuronium injection when pro- found relaxation(PTC=0) was confirmed. Rabbits(n=60) were randomly allocated to 4 groups. After pancuranium 0.2mg/kg IV, the onset and recovery times were evalusted. When the profound relaxation(PTC=0) was confirmed at Smin. after pancuronium injection, neostigmine 50 ug/kg and atropine sulfate (atropine) 20 ug/kg were injected in group 1. At thst time, neostigmine 10/kg and atropine 4 ug/kg were injected and after 3min. neostigmine 40/kg and atropine 16 ug/kg were injected in group 2. At that time, pyridostigmine 250 ug/kg and atropine 20 ug/kg were injected in group 3. At that time, pyridostigmine 50 ug/kg and atropine 4 ug/kg were injected and after 3min. pyridostigmine 200 ug/kg and atropine 16 ug/kg were injected in group 4. The results were as follows :. 1) The time until 75% recovery of twitch amplitude was 53.1+/-12.4min. in group 1, 44.9+/-212.1min. in group 2, 54.9+/-9.7min. in group 3 and 48.2+/-7.1min. in group 4. The reversal times were tended to reduce when the reversal agents were administered with "priming principle" at the profound relaxation. 2) At the profound relaxation the reversal effects of neostigmine were greater than that of pyridostigmine.

The Effects of Metocurine Iodine and Vecuronium Bromide on Intraocular Pressure with the Priming Principle / 대한마취과학회지

We measured the intraocular pressure changes in forty female patients (aged from 20 to 50) without a history of ocular or cardiovascular disease who were classified physical status 1 and 2, and scheduled for elective surgery. They were divided into 4 groups. Group l (n=10); metocurime 0.03 mg/kg as a priming dose and metocurine 0.27 mg/ kg as a intubating dose. Group 2 (n= 10); vecuronium 0.008 mg/kg as a priming dose and vecuronium 0.072 mg as a intubating dose. Group 3 (n=10); vecuronium 0.008mg/kg as a priming dose and metocurine 0.27 mg/kg as a intubating dose. Group 4 (n=10); metocurine 0.03mg/kg as a priming dose and vecuronium 0.072 mg/kg as a intubating dose. In this study, metocurine and vecuronium were used with the priming principle. We also measured changes in blood pressure, pulse rate and T1% of Train of four stimulation and evaluated the discomfort after the administration of the priming dose and the difficulties of intubation. The results were as follows, 1) Compared with the control value, there was no increse in intraocular pressure following intubation in all four groups and intraocular pressure of 2 and 4 minutes following intubation decreased significantly in all four groups. The greatest decrease was seen in group 3, but it was not significant when compared to the other three groups. 2) While a transient increase in blood pressure was seen in all four groups, the lowest increase was seen in group 3 as compared to the control value. Blood pressure 4 minutes following intubation decreased significantly in grop 3. 3) A significant decrease in the T1% of the Train of four stimuli at one minute after administration of the intubating dose was seen in group 3 compared to the other three groups. 4) Group 3 showed the lowest number of difficult intubation. In conclusion, the combination of vecuronium and metoeurine with the priming principle provide optimal conditions for smooth and rapid intubation with no elevation of intraocular pressure, blood pressure and heart rate changes for ocular surgery.

The Effect of Neostigmine Pretreatment on Vecuronium Induced Neuromuscular Blockade / 대한마취과학회지

Prolonged neuromuscular blockade following succinylcholine may be seen when anticho- linesterase had been administered prior to reverse nondepolarizing muscle relaxant-induced paralysis, possibly anticholinesterase has been reported to inhibit serum cholinesterase activity. Our study was undertaken in order to understand the effect of a nondepolarizing muscle relaxant (vecuronium) following neostigmine pretreatment. In this study, we assessed the effect of vecuronium induced neuromuscular blockade using a train of four, 2 Hz stimulations on ulnar nerve. Patients admitted to our hospital for elective operations were divided into two groups, each group consisting of 16 patients. In group I, vecuronium 0.1 mg/kg was .administered according to the priming principle following normal saline, in group II, vecuronium 1.0mg/kg was administered according to the priming principle following neostigmine 0.05 mg/kg and glycopyrrolate 0.003 mg/kg pretreatment. Then the time for Tl to reach 5% or less(second), and the time for Tl to reach from 25% to 75%(recovery index) were measured in both groups. The time for Tl to reach 5% or less in group I(92.8+/-14.72 second) and group II(97.5+/-16.43 seconds) were not siginificant. However the recovery indexof group I(10.2 5+/-1.93 minute) and group II(8.5+/-1.80 minute) showed significant shortening in group II(p<0. 05)

Clinical Evaluation of the Two Times Priming and Pancuronium as a Priming of Vecuronium for Endotracheal Intubation / 대한마취과학회지

The individual onset of action of pancuronium and vecuronium has been examined with a priming dose of same or the other agent or two times priming. Measurement of changes in the Tl% of TOF ratio of the adductor pollicis muscle were performed by Accelograph (Biometer). Sixty adult patients were administered Vecuronium(V) 0.015mg/kg (group 1), V 0.005mg/kg 3 minutes after 0.01mg/ kg(group 2), Pancuronium(P) 0. 015 mg/kg(group 3,4) as a priming agents. After 5 minutes, the intubating dose of V 0.085mg/kg (group 1,2,3), P 0.085 mg/kg (group 4) were administered with the induction agent, thiopental sodium 5 mg/kg. All sixty patients underwent orotracheal intubation at 60 seconds after the injection of intubating dose. Intubation condition, reduction of Tl% at 60 seconds, the onset time of maximal blockade (Tl 0%) were evaluated. There was no difficulty in intubation. Fifty-two (86%) patients were distributed in exellent and satisfactory grade of largest in group 2. While group 3 showed more rapid than group 4, group 2 showed the most rapid onset time significantly. These results indicate that the twicely divided dose of vecuronium for priming agent may be adequate and vecuronium after priming with pancuronium is more rapid than priming with same agent.

Clinical Evaluation of Atracurium for Endotracheal Intubation / 대한마취과학회지

The usefulness of nondepolarizing muscle relaxants for intubation is limited by a relatively slow onset of neuromuscular block compared to that achived with succinylcholine. But, authors have reported that larger doses of nondepolarizing muscle relaxants produce a more rapid onset of maximal neuromuscular block and conditions conductive to endotracheal intubation and recent reports support the use of the "priming principle in the clinical practice of anesthesiology. This phenomenon may apply to all nondepolarizing relaxants: it is reported to facilitated neuromuscular blockade and tracheal intubation when used with atracurium, vecurouium, alcuronium or pancuronium. In this study, administering a small subclinical dose of atracurium (75ug/kg) Smin. prior to the remainder of an intubating doae of atracurium (250ug/kg) had no different on grade of block for intubation compared to single IV bolus of atracurium (500ug/kg).

Clinical Evaluation of Atracurium for Endotracheal Intubation / 대한마취과학회지

The usefulness of nondepolarizing muscle relaxants for intubation is limited by a relatively slow onset of neuromuscular block compared to that achived with succinylcholine. But, authors have reported that larger doses of nondepolarizing muscle relaxants produce a more rapid onset of maximal neuromuscular block and conditions conductive to endotracheal intubation and recent reports support the use of the "priming principle in the clinical practice of anesthesiology. This phenomenon may apply to all nondepolarizing relaxants: it is reported to facilitated neuromuscular blockade and tracheal intubation when used with atracurium, vecurouium, alcuronium or pancuronium. In this study, administering a small subclinical dose of atracurium (75ug/kg) Smin. prior to the remainder of an intubating doae of atracurium (250ug/kg) had no different on grade of block for intubation compared to single IV bolus of atracurium (500ug/kg).

The Effects of Vecuronium Bromide in Divided Dose on Endotracheal Intubation / 대한마취과학회지

Succinylcholine chloride is ordinarily the muscle relaxant of choice for rapid endotracheal intubation, but may produce myalgia, increase in intragastric pressure, increase in intraocular pressure, and it may be associated with malignant hyperthermia and hyperkalemia. Many investigators have tried to find an alternative drug for succinylcholine chloride. Foldes reported that the onset can be shortened by the administration of a subparalyzing dose of vecuronium bromide a nondepolarizing intermediate-acting muscle relaxant, prior to its intubating dose. This has been termed "the priming principle",. Mehta et al, Lennon et al and Schwarz reported similar results. These investigators studied to identify an optimal priming dose, priming interval (the time from the priming dose to the intubating dose) and intubating dose of vecuronium bromide, to perform a rapidsequence induction of anesthesia. We studied 50 healthy adult patients, and results are 1) Group IV (a priming dose of 0.02 mg/kg, a priming interval of 4 min and an intuating dose of 0. 1 mg/kg) had better intubating condition than the control group. 2) The groups with divided doses had significantly shorter onset time compared to the control group (0.1 mg/kg without prime dose). 3) Group II and IV (priming dose 0.02 mg/kg) had shorter onset time compared to group I and III (priming dose 0.01 mg/kg), but the difference was not significant. 4) Group III and IV (priming interval of 4 min) had shorter onset time compared to group I and II (priming interval of 2 min), but the difference was not significant. In conclusion, group IV (priming dose of 0.02 mg/kg and priming interval of 4 min) had the shortest onset time and provided the best intubating condition.