Clinical Research Article : Priming technique can alleviate the withdrawal responses associated with intravenous administration of rocuronium

Jae In Lee,Se Hun Lim,Sang Eun Lee,Young Hwan Kim,Jeong Han Lee,Kun Moo Lee,Soon Ho Cheong,Young Kyun Choe,Young Jae Kim,Chee Mahn Shin 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.56 No.6

Background: Intravenous injection of rocuronium is associated with withdrawal responses which are attributable to the pain from the injection of rocuronium. Several methods have been proposed to abolish and attenuate rocuronium-induced pain. We hypothesized priming dose of rocuronium could reduce withdrawal responses associated with administering a second large dose of rocuronium for tracheal intubation. We compared the efficacy of the priming dose technique of rocuronium with intravenous lidocaine as a pre-treatment for the prevention of withdrawal responses associated with rocuronium injection. Methods: We recruited 150 patients aged between 18 and 60 years, ASA physical status 1 or 2, who were going to undergo elective surgery requiring general anesthesia. Patients were allocated into three groups. Group C received normal saline, Group L received lidocaine 1 mg/kg, and Group P received rocuronium 0.06 mg/kg 2 minutes before administering a second large dose of rocuronium for tracheal intubation. After the loss of consciousness, rocuronium 0.6 mg/kg was administered intravenously over 10 seconds for tracheal intubation. The withdrawal responses to the injection of rocuronium were evaluated. Results: The incidence of withdrawal responses associated with rocuronium injection for tracheal intubation was 56, 50, 24% in group C, group L, and group P, respectively. The incidence of withdrawal responses was lower in group P than group C and group L, but there was no difference between group L and group C. Conclusions: Priming dose technique is a useful clinical method to alleviate withdrawal responses associated with rocuronium injection. (Korean J Anesthesiol 2009; 56: 628~33)

The antagonistic effect of neostigmine on rocuronium-, clindamycin-, or both-induced neuromuscular blocking in the rat phrenic nerve-hemidiaphragm

Seung Soo Kim,이수일,정찬종,이승철 대한마취통증의학회 2011 Korean Journal of Anesthesiology Vol.61 No.4

Background: Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuroniuminduced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB. Background: Neostigmine augments clindamycin-induced neuromuscular block and antagonizes rocuroniuminduced neuromuscular block; however, it remains unclear whether neostigmine enhances the neuromuscular blocking (NMB) that is caused by combinations of rocuronium and clindamycin. The intent of this study was to determine whether neostigmine potentiates the muscle relaxation that is induced by combinations of rocuronium and clindamycin and to estimate whether both clindamycin and rocuronium have synergistic actions on NMB. Methods: Forty-one left phrenic nerve-hemidiaphragms (from male Sprague-Dawley rats, 150-250 g) were mounted in Krebs solution. Three consecutive single twitches (ST, 0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained for each increase in concentration of rocuronium or clindamycin. The concentrations of rocuronium were cumulatively increased until an 80% to 90% reduction in ST was attained in the Krebs solutions pre-treated with 0(n = 5), 0.1 (n = 1), 0.25 (n = 1), 0.5 (n = 4), or 1.0 (n = 1) mM clindamycin or with 0 (n = 4), 0.1 (n = 1), 0.5 (n = 5), 1.0(n = 5), or 2.0 (n = 4) mM clindamycin in combination with 250 nM neostigmine, and so were the concentrations of clindamycin in the Krebs solutions pre-treated with 0 (n = 6) or 250 nM (n = 6) neostigmine. Results: Clindamycin increased the potency of rocuronium for ST and tetanic fade, irrespective of the presence of neostigmine. Neostigmine shifted the concentration-response curve of rocuronium to the right in the presence or absence of clindamycin. The interaction between rocuronium and clindamycin was synergistic when clindamycin concentrations were in excess of 0.5 mM, irrespective of the presence of neostigmine. Conclusions: Neostigmine may partially antagonize the neuromuscular block that is induced by a combination of clindamycin and rocuronium. Clinicians are advised to be aware that clindamycin synergistically increases the degree of rocuronium-induced neuromuscular block, even when neostigmine is present.

Single pretreatment of remifentanil may reduce pain after propofol and rocuronium injection in rapid sequence induction

최윤지,박한석,이한,윤승주 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.63 No.5

Background: We designed this double-blind, placebo-controlled study to compare the efficacy of remifentanil in reducing the pain of both propofol and rocuronium injection during rapid-sequence induction. Methods: Ninety-five patients, scheduled for elective surgery under general anesthesia, were divided into 3 groups:saline (Group S, n = 31), remifentanil 1 μg/kg (Group R, n = 32), and lidocaine 1.5 mg/kg (Group L, n = 32) were administered after tourniquet application. The occlusion was released after 1 min and 5 ml of 1% propofol was injected over 10 s. Pain on propofol injection was evaluated by a 10-point verbal numeric rating scale (VNRS). The rest of the induction dose of propofol and 1 mg/kg of rocuronium, were injected. Pain on rocuronium injection was evaluated by a four-point score (FPS). Results: The VNRS of propofol injection was as follows: R (0.78) = L (1.34) < S (4.26). The incidence of withdrawal response due to rocuronium was as follows: R (6.3%) < L (53.1%) < S (83.9%). The FPS of rocuronium injection was as follows: R (0.81) < L (1.78) < S (2.93). Conclusions: Pretreatment with a bolus of remifentanil was effective in simultaneously reducing injection pain of propofol and rocuronium. In addition, remifentanil pretreatment was more effective in suppression of withdrawal response by rocuronium than lidocaine. Background: We designed this double-blind, placebo-controlled study to compare the efficacy of remifentanil in reducing the pain of both propofol and rocuronium injection during rapid-sequence induction. Methods: Ninety-five patients, scheduled for elective surgery under general anesthesia, were divided into 3 groups:saline (Group S, n = 31), remifentanil 1 μg/kg (Group R, n = 32), and lidocaine 1.5 mg/kg (Group L, n = 32) were administered after tourniquet application. The occlusion was released after 1 min and 5 ml of 1% propofol was injected over 10 s. Pain on propofol injection was evaluated by a 10-point verbal numeric rating scale (VNRS). The rest of the induction dose of propofol and 1 mg/kg of rocuronium, were injected. Pain on rocuronium injection was evaluated by a four-point score (FPS). Results: The VNRS of propofol injection was as follows: R (0.78) = L (1.34) < S (4.26). The incidence of withdrawal response due to rocuronium was as follows: R (6.3%) < L (53.1%) < S (83.9%). The FPS of rocuronium injection was as follows: R (0.81) < L (1.78) < S (2.93). Conclusions: Pretreatment with a bolus of remifentanil was effective in simultaneously reducing injection pain of propofol and rocuronium. In addition, remifentanil pretreatment was more effective in suppression of withdrawal response by rocuronium than lidocaine.

At therapeutic concentration bupivacaine causes neuromuscular blockade and enhances rocuronium-induced blockade

이지현,이수일,이승철,최소론,이원지 대한마취통증의학회 2012 Korean Journal of Anesthesiology Vol.62 No.5

Background: Partially paralyzed patients may be placed in the risk of pharyngeal dysfunction. Bupivacaine acts as acetylcholine receptor ion channel blocker and may synergistically interact with rocuronium to augment NM blockade. Thus, this study aims to elucidate whether or not, at a therapeutic concentration, bupivacaine by itself may cause NM blockade and reduce an effective concentration of rocuronium. Methods: Twenty-two left phrenic nerve-hemidiaphragms (Male SD rats, 150-250 g) were hung in Krebs solution. Three consecutive ST, 0.1 Hz and one TT, 50 Hz for 1.9 s were obtained before drug application and at each new drug concentration. A concentration of bupivacaine in Krebs solution (n = 5) was cumulatively increased by way of 0.01, 0.1, 1, (1, 2, 3, 4, 5, 6, 7) × 10 μM. In a Krebs solution, pre-treated with bupivacaine 0 (n = 5), 0.1 (n = 5), 1.0 (n = 5), 10 (n = 2) μM, and then concentrations of rocuronium were cumulatively increased by way of 1, 3, 5, 7, 9, 12, 14, 16, 18, 20 μM. EC for each experiment were determined by a probit. The EC50’s of rocuronium were compared using a Student’s t-test with Bonferroni’s correction. Differences were considered significant when P < 0.05. Results: The potency of bupivacaine for normalized TF was 11.4 (± 1.1) μM. Below 30 μM of bupivacaine, the single twitch potentiation sustained despite the development of tetanic fade and partial inhibition of PTT. Bupivacaine significantly facilitated the NM blockade induced by rocuronium. Conclusions: Clinicians should be aware that bupivacaine by itself at its therapeutic concentration inhibit NM conduction and enhances rocuronium-induced muscle relaxation. Background: Partially paralyzed patients may be placed in the risk of pharyngeal dysfunction. Bupivacaine acts as acetylcholine receptor ion channel blocker and may synergistically interact with rocuronium to augment NM blockade. Thus, this study aims to elucidate whether or not, at a therapeutic concentration, bupivacaine by itself may cause NM blockade and reduce an effective concentration of rocuronium. Methods: Twenty-two left phrenic nerve-hemidiaphragms (Male SD rats, 150-250 g) were hung in Krebs solution. Three consecutive ST, 0.1 Hz and one TT, 50 Hz for 1.9 s were obtained before drug application and at each new drug concentration. A concentration of bupivacaine in Krebs solution (n = 5) was cumulatively increased by way of 0.01, 0.1, 1, (1, 2, 3, 4, 5, 6, 7) × 10 μM. In a Krebs solution, pre-treated with bupivacaine 0 (n = 5), 0.1 (n = 5), 1.0 (n = 5), 10 (n = 2) μM, and then concentrations of rocuronium were cumulatively increased by way of 1, 3, 5, 7, 9, 12, 14, 16, 18, 20 μM. EC for each experiment were determined by a probit. The EC50’s of rocuronium were compared using a Student’s t-test with Bonferroni’s correction. Differences were considered significant when P < 0.05. Results: The potency of bupivacaine for normalized TF was 11.4 (± 1.1) μM. Below 30 μM of bupivacaine, the single twitch potentiation sustained despite the development of tetanic fade and partial inhibition of PTT. Bupivacaine significantly facilitated the NM blockade induced by rocuronium. Conclusions: Clinicians should be aware that bupivacaine by itself at its therapeutic concentration inhibit NM conduction and enhances rocuronium-induced muscle relaxation.

임상연구 : 소아에서 0.9% NaCl에 희석한 Rocuronium의 정주가 회피반응의 빈도 및 강도에 미치는 억제효과

박상진 ( Sang Jin Park ),이주영 ( Joo Young Lee ),지대림 ( Dae Lim Jee ) 대한마취과학회 2006 Korean Journal of Anesthesiology Vol.51 No.2

Background: Rocuronium is suitable for short operations and rapidly controlling the airway on account of its rapid onset and intermediate action. However, the intravenous administration of rocuronium can cause pain and withdrawal movement in children. This study evaluated the effect of diluting rocuronium from 10 mg/ml to 1 or 0.67 mg/ml with 0.9% NaCl on the withdrawal response associated with the intravenous administration of rocuronium with the intubation dose. Methods: Ninety pediatric patients undergoing general anesthesia were randomized into one of three groups; Group OR (only rocuronium 0.6 mg/kg, n = 30), Group SRl0 (rocuronium 0.6 mg/kg diluted with 0.9% NaCl to 1 mg/ml, n = 30), Group SR15 (rocuronium 0.6 mg/kg diluted with 0.9% NaCl to 0.67 mg/ml, n = 30). After the loss of consciousness by a thiopental sodium 5 mg/kg injection, the patients from each group received the 0.6 mg/kg premixed rocuronium, respectively. Patients` withdrawal response to the injection were graded using a 4-point scale (Grade 0, 1, 2, 3). Results: The incidence and the intensity of the withdrawal response were significantly lower in the SRl0 and SR15 groups than in the OR group (P < 0.05). In the SR15 group, the intensity of the withdrawal response was under grade 2 in all patients. Conclusions: Diluting rocuronium to 0.67 mg/ml is a simple and effective method for preventing withdrawal movements during an intravenous rocuronium injection. (Korean J Anesthesiol 2006; 51: 157~61)

중탄산나트륨의 사용이 Rocuronium의 정주통과 작용 발현에 미치는 영향

구의경,황정원,김현주,나효석,박희평,전영태,도상환 대한마취통증의학회 2009 Anesthesia and pain medicine Vol.4 No.3

Background: Rocuronium is a commonly used muscle relaxant, however, it has severe injection pain. We supposed that injection pain of rocuronium was due to acidity of solution. We studied whether pH elevation of rocuronium with bicarbonate relieves injection pain. Methods: We included 140 adult patients with 18 G intravenous catheter in arm for general anesthesia and they were randomly allocated to two groups. All patients received 0.6 mg/kg of rocuronium, one group (Group C) received rocuronium only (pH = 4.04) and the other group (Group B) received bicarbonate mixed rocuronium (rocuronium: bicarbonate = 5 ml : 1 ml, pH of mixture = 7.14). The severity (none, mild, severe) of injection pain was assessed. Just after assessment, 5 mg/kg of thiopental was injected for loss of conciousness. Twitch of supramaximal stimuli was monitored and intubation time was considered the interval from injection to 75% depression and onset time the interval from injection to maximal depression. Results: The incidence of injection pain of group C was 96.9% and 18.8% in group B (P < 0.01). Intubation time and onset time were 79.5 ± 24.4 sec and 114.3 ± 43.6 sec in group C and 80.6 ± 27.0 sec and 115.2 ± 46.2 sec in group B. There was no significant difference between groups. Conclusions: Our result shows that adding bicarbonate to rocuronium is effective to relieve injection pain of rocuronium without change of onset of rocuronium.

저용량의 Rocuronium을 사용한 기관내 삽관 시 사전예비정주법이 Rocuronium의 작용 발현시간과 삽관 조건에 미치는 영향

손윤숙 ( Yoon Suk Son ),정규돈 ( Kyu Don Chung ),조현숙 ( Hyun Sook Cho ),유승준 ( Sung Jun Yu ),김수화 ( Su Hwa Kim ),이상묵 ( Sang Mook Lee ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.57 No.4

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. (Korean J Anesthesiol 2009;57:444∼9)

당뇨병 환자에서 Rocuronium이 심박수 변이도에 미치는 영향

공형윤 ( Hyung Youn Kong ),이정석 ( Jeong Seok Lee ),서상원 ( Sang Won Seo ),조성환 ( Sung Hwan Cho ),김상현 ( Sang Hyun Kim ),채원석 ( Won Seok Chae ),진희철 ( Hee Cheol Jin ),김용익 ( Yong Ik Kim ) 대한마취과학회 2009 Korean Journal of Anesthesiology Vol.57 No.2

Background: Clinically rocuronium, a muscle relaxant, has no significant inhibitory effect on the autonomic nervous system in the healthy population. However, there has been no study done on rocuronium in diabetic patients. Therefore, we used heart rate variability (HRV) as a biomarker to investigate cardiac autonomic function after rocuronium administration to diabetic patients. Methods: In 21 diabetic adult patients, heart rate (HR), mean arterial blood pressure (BP), low frequency (LF, 0.04-0.15 Hz) power, high frequency (HF, 0.15-0.4 Hz) power, LF/HF ratio, SD1 and SD2 in the Poincare plot before induction of anesthesia, and immediately before and after rocuronium administration were calculated and compared. Results: HR, mean BP, LF, LF/HF ratio and SD2 after rocuronium administration did not differ significantly from the measurements taken before rocuronium administration. HF and SD1 decreased significantly after rocuronium administration (P=0.022, P=0.019 respectively). Covariates such as age, gender, weight, duration of diabetes mellitus and hypertension did not alter the effect of rocuronium on the autonomic nervous system. Conclusions: Rocuronium produced a significant decrease in parasympathetic activity. Therefore, further study will be needed to determine whether vagal reduction caused by rocuronium could have potential to deteriorate hemodynamics in diabetic patients. (Korean J Anesthesiol 2009;57:165∼9)

Rocuronium 정주 시 발생하는 통증에 Sodium Bicarbonate 또는 Lidocaine의 혼합 정주가 미치는 영향

김용호,최영순,이우경,채영근 關東大學校 醫科大學 醫科學硏究所 2004 關東醫大學術誌 Vol.8 No.2

Background: Rocuronium produces intense pain on intravenous injection in conscious patients. The aim of this study was to evaluate the effectiveness of mixing rocuronium with sodium bicarbonate or lidocaine on the pain associated with intravenous administration of rocuronium in conscious patients. Methods: Thirty patients who needed surgical procedure under general anesthesia were randomized into three groups. Group I received rocuronoium 50 mg plus saline 5 ml, group 2 received rocuronium 50 mg plus 2% lidocaine 2 ml plus saline 3 ml and group 3 received rocuronium 50 mg plus 8.4% sodium bicarbonate 3 ml plus saline 2 ml. The patients were then observed and asked if they experienced pain or discomfort during injection. Results: The incidence rate of pain on injection of rocuronium was more reduced in group 2, and 3 than in group 1. Moderate to severe pain did not occur in group 3. Conclusion: In conscious patients, mixing sodium bicarbonate with rocuronium is simple and effective for preventing pain during intravenous injection of rocuronium.

실험연구 : Nicorandil이 Rocuronium의 약력학에 미치는 효과

이수일 ( Soo Il Lee ),이종환 ( Jong Hwan Lee ),이승철 ( Seung Cheol Lee ),이정무 ( Jung Moo Lee ) 대한마취과학회 2006 Korean Journal of Anesthesiology Vol.50 No.5

Background: Some investigators have shown that nicorandil, a KATP channel opener, depresses the neuromuscular transmission contraction of the skeletal muscle. However, others have reported that it improves the recovery of vecuronium relaxation and the myotonic activity of muscle. This study investigated the effect of nicorandil on rocuronium relaxation. Methods: Hemidiaphragm-phrenic nerve preparations were obtained from male Sprague-Dawley rats (150-250 g). The preparations were bathed in Krebs` solution containing in (mM): NaCl 118, KCl 5, CaCl2 2.5, NaHCO3 30, KH2PO4 1, MgCl2 1 and glucose 11. The preparations were, then maintained at 32℃ and aerated with a mixture of 95% O2 and 5% CO2. Isometric forces that were generated in response to 0.1 Hz, and, 50 Hz for 1.9 seconds with supramaximal electrical stimulation (0.2 msec, rectangular) to the phrenic nerve were measured using a force transducer. The single twitch tension (ST) and peak tetanic tension (PTT) were calculated as % inhibition of the control, and the tetanic fade (TF), as % increase in the PTT. Each preparation was exposed to one of the 6 nicorandil concentrations (0.0, 0.625, 1.25, 2.5, 5, 10μM), and the adequate volume of the rocuronium solution was cumulatively added to the tissue bath for a desired rocuronium concentration until there was an 80-90% decrease in the ST. The effect of rocuronium at each concentration was allowed to reach a steady state before the tension parameters were measured. The EC5, EC25, EC50, EC75, and EC95 of rocuronium for the ST, PTT and TF were calculated using a probit model. The differences between the EC50 of rocuronium according to the nicorandil concentrations were tested using a t-test and a Bonferroni`s correction. Results: 1.25 and 2.5μM nicorandil shifted the cumulative concentration-response curves for the TF of rocuronium to the right. 5 and 10μM nicorandil shifted the cumulative concentration-response curves for the ST of rocuronium to the left. Conclusions: Lower concentration of nicorandil may help maintain the tetanic contraction during rocuronium relaxation. (Korean J Anesthesiol 2006; 50: 567~71)