BACKGROUNDThe antagonistic actions of anticholinesterase drugs on non-depolarizing muscle relaxants are theoretically related to the activity of acetylcholinesterase (AChE) in the neuromuscular junction (NMJ). However, till date the changes of AChE activity in the NMJ during sepsis have not been directly investigated. We aimed to investigate the effects of sepsis on the antagonistic actions of neostigmine on rocuronium (Roc) and the underlying changes of AChE activity in the NMJ in a rat model of cecal ligation and puncture (CLP).

METHODSA total of 28 male adult Sprague-Dawley rats were randomized to undergo a sham surgery (the sham group, n = 12) or CLP (the septic group, n = 16). After 24 h, the time-response curves of the antagonistic actions of 0.1 or 0.5 μmol/L of neostigmine on Roc (10 μmol/L)-depressed diaphragm twitch tension were measured. Meanwhile, the activity of AChE in the NMJ was detected using a modified Karnovsky and Roots method. The mRNA levels of the primary transcript and the type T transcript of AChE (AChET) in the diaphragm were determined by real-time reverse transcription-polymerase chain reaction.

RESULTSFour of 16 rats in the septic group died within 24 h. The time-response curves of both two concentrations of neostigmine in the septic group showed significant upward shifts from those in the sham group (P < 0.001 for 0.1 μmol/L; P = 0.009 for 0.5 μmol/L). Meanwhile, the average optical density of AChE in the NMJ in the septic group was significantly lower than that in the sham group (0.517 ± 0.045 vs. 1.047 ± 0.087, P < 0.001). The AChE and AChETmRNA expression levels in the septic group were significantly lower than those in the sham group (P = 0.002 for AChE; P = 0.001 for AChET).

CONCLUSIONSSepsis strengthened the antagonistic actions of neostigmine on Roc-depressed twitch tension of the diaphragm by inhibiting the activity of AChE in the NMJ. The reduced content of AChE might be one of the possible causes of the decreased AChE activity in the NMJ.

Acetylcholinesterase ; metabolism ; Androstanols ; pharmacology ; Animals ; Cecum ; injuries ; Cholinesterase Inhibitors ; pharmacology ; Diaphragm ; drug effects ; metabolism ; Disease Models, Animal ; Ligation ; Male ; Neostigmine ; pharmacology ; Neuromuscular Junction ; enzymology ; Neuromuscular Nondepolarizing Agents ; pharmacology ; Punctures ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Sepsis ; physiopathology

BACKGROUNDRecurarization has previously been described in the context of acute normovolemic hemodilution. The aim of this study was to investigate the impairment of recovery of neuromuscular function after re-transfusion of intraoperative salvaged blood in patients treated with rocuronium.

METHODSWe enrolled 50 patients undergoing general anesthesia for lumbar surgery. Intraoperative blood salvage (IBS) was used in 30 patients (group I); the remaining 20 comprised a control group (group C). Anesthesia was induced with fentanyl, midazolam, propofol and rocuronium. Rocuronium was infused to maintain neuromuscular blockade during surgery. Blood was collected from the operative field and re-transfused in the post-anesthesia care unit (PACU). Neuromuscular function was monitored using the train-of-four ratio (TOFr). Once the train-of-four ratio exceeded 90 in the PACU, neuromuscular function was evaluated every 5 minutes for 30 minutes. The TOFr and incremental recovery of TOFr from baseline were recorded. Salvaged blood was re-transfused at the beginning of the evaluation for patients in group I, and afterwards for patients in group C. Blood gas analysis was assessed before anesthesia and in the PACU.

RESULTSIncremental recovery of TOFr from baseline was significantly less in group I than controls at 25 minutes (6.1 ± 3.2 vs. 9.1 ± 3.2, respectively; P = 0.001) and 30 minutes (7.1 ± 3.2 vs. 10.0 ± 2.2, respectively; P = 0.001). There were no significant differences in gas exchange between the groups.

CONCLUSIONSIn patients who had received a rocuronium infusion during anesthesia, re-transfusion of salvaged blood significantly impaired recovery of neuromuscular function recovery in the PACU, but without significant impairment of respiratory function.

Adolescent ; Adult ; Aged ; Androstanols ; adverse effects ; therapeutic use ; Anesthesia, General ; methods ; Blood Gas Analysis ; Female ; Humans ; Male ; Middle Aged ; Muscle, Skeletal ; innervation ; Neuromuscular Blocking Agents ; adverse effects ; therapeutic use ; Young Adult

BACKGROUND: Bupivacaine, clindamycin, and gentamicin inhibit neuromuscular (NM) conduction. When they are combined, they may synergistically reduce the effective concentration of each to the therapeutic concentration in augmenting rocuronium-induced NM block. Thus, the aim of this study was to investigate whether combinations of the three drugs, at around their therapeutic concentrations, potentiate rocuronium-induced NM block. METHODS: Fifty-seven left-phrenic nerve hemidiaphragms (Male S-D rats, 150-250 g) were hung in a 20-ml organ bath filled with Krebs solution. Three consecutive single-twitch tensions (0.1 Hz) and one tetanic tension (50 Hz for 1.9 s) were obtained. A Krebs solution was premixed with concentration sets of bupivacaine and clindamycin, bupivacaine and gentamicin, or bupivacaine, clindamycin and gentamicin. Then, the concentration of rocuronium was cumulatively increased in the Krebs solution (1, 3, 5, 7, 9, 12, 14, 16, 18, and 20 microM) until an 80% to 90% reduction in single twitch was attained. The effective concentrations for each experiment were determined with the probit model. RESULTS: The combinations of bupivacaine, clindamycin, and gentamicin enhanced rocuronium-induced NM block. When the three drugs were applied simultaneously, their concentrations were reduced to near-therapeutic levels in potentiating the action of rocuronium. CONCLUSIONS: Bupivacaine, clindamycin, and gentamicin blocked NM conduction, and when all three drugs were applied together, they augmented rocuronium-induced NM block at their near-therapeutic concentrations. Clinicians should be aware of the cooperability in NM block between drugs that interrupt NM conduction.
Androstanols ; Animals ; Baths ; Bupivacaine ; Clindamycin ; Gentamicins ; Isotonic Solutions ; Neuromuscular Blockade ; Rats

BACKGROUND: The Pentax Airway Scope (AWS) is a video laryngoscope designed to facilitate tracheal intubation with a high-resolution image. The Pentax AWS has been reported to cause less hemodynamic stress than the Macintosh laryngoscope. The aims of this study are to investigate the differences in hemodynamic responses and norepinephrine concentrations to tracheal intubation between procedures using he Pentax AWS and the Macintosh laryngoscope. METHODS: Forty patients (American Society of Anesthesiologists class I-II, age range: 18-60 years) were randomly assigned to be intubated with either the Pentax AWS or the Macintosh laryngoscope while under general anesthesia. Routine monitoring, including invasive arterial blood pressure and bispectral index, were applied. Thiopental (4 mg/kg), fentanyl (1 microg/kg), midazolam (0.05 mg/kg), and rocuronium (0.6 mg/kg) were administered for anesthetic induction. Systolic, diastolic, and mean blood pressures and heart rates were recorded pre-intubation, immediately post-intubation (T0), and over the following 10 minutes at one minute intervals (T1, T2, T3, T4, T5em leaderT10). Patient blood was sampled for norepinephrine concentrations pre-intubation (baseline) and post-intubation (T1). Evidence of sore throat was evaluated 30 min and 24 hr after extubation. Data were transformed to % basal and expressed as mean +/- SD. RESULTS: The systolic, diastolic, and mean blood pressure, and heart rate at T0 and T4 were significantly different between the two groups. There was no significant difference in plasma norepinephrine between the two groups. The difference in incidence of sore throat was not significant between the two groups. CONCLUSIONS: Pentax-AWS for tracheal intubation has greater hemodynamic stability than the Macintosh blade laryngoscope.
Androstanols ; Anesthesia, General ; Arterial Pressure ; Blood Pressure ; Fentanyl ; Heart Rate ; Hemodynamics ; Humans ; Incidence ; Intubation ; Laryngoscopes ; Midazolam ; Norepinephrine ; Pharyngitis ; Plasma ; Thiopental

BACKGROUND: Gentamicin reduces acetylcholine release and clindamycin causes end-plate ion channel blockade. Because of these reasons, two drugs show muscular relaxant effect and potentiate the action of nondepolarizing neuromuscular agents. This study was intended to evaluate the effect of gentamicin and clindamycin on rocuronium-induced neuromuscular blockade and the interaction between these drugs. METHODS: Male Sprague-Dawley rats' phrenic nerves and diaphragms were installed in a bath containing Krebs solution. They were divided into three study groups. The first group was pre-treated with 0.1 (n = 3), 0.2 (n = 4) or 0.5 (n = 3) mM gentamicin and the tension was measured as the concentration of rocuronium was increased. The second group was experimented by increasing gentamicin on 0.25 (n = 5), 0.5 (n = 6) or 1.0 (n = 6) mM clindamycin. The final group was pre-treated with various combinations of gentamicin and clindamycin. The drug concentration was gradually increased until single twitch tension decreased by around 80%. Effective concentration was calculated using a probit model and interaction indices derived the Loewe additivity. RESULTS: The administration of gentamicin and the combination of gentamicin and clindamycin enhanced rocuronium-induced neuromuscular blockade. At 0.2 and 0.5 mM gentamicin, synergistic interactions with rocuronium were observed. Likewise, at 0.5 and 1.0 mM clindamycin, synergistic interactions with gentamicin appeared. When all three drugs were combined, in the tetanic fade, all the groups except for those administered with 0.01 mM gentamicin and 0.25 mM clindamycin showed synergistic interactions. CONCLUSIONS: This study demonstrate that gentamicin and clindamycin potentiated rocuronium induced neuromuscular blockade. Moreover, it was found that these drugs interacted synergistically.
Acetylcholine ; Androstanols ; Baths ; Clindamycin ; Diaphragm ; Gentamicins ; Humans ; Ion Channels ; Isotonic Solutions ; Male ; Neuromuscular Agents ; Neuromuscular Blockade ; Phrenic Nerve ; Refractory Period, Electrophysiological

BACKGROUND: Rapid sequence induction (RSI) is indicated in various situations. Succinylcholine has been the muscle relaxant of choice for RSI, and rocuronium has become an alternative medicine for patients who cannot be administered succinylcholine for various reasons. Although rocuronium has the most rapid onset time among non-depolarizing muscle relaxants, the standard dose of rocuronium (0.6 mg/kg) takes 60 seconds to achieve appropriate muscle relaxation. We evaluated intubating conditions using the "modified timing principle" with rocuronium and succinylcholine. METHODS: In this prospective controlled blinded study, all patients received 1.5 microg/kg fentanyl intravenously with preoxygenation for 2 minutes and were randomized to receive 0.6 mg/kg rocuronium followed by 1.5 mg/kg propofol or 1.5 mg/kg propofol and 1.5 mg/kg succinylcholine. The rocuronium group was intubated just after confirming loss of consciousness, and the succinylcholine group was intubated 1 minute after injecting succinylcholine. Intubation condition, timing of events, and complications were recorded. RESULTS: All patients were successfully intubated in both groups. Apnea time of the rocuronium group (38.5 seconds) was significantly shorter than that in the succinylcholine group (100.7 seconds). No significant differences were observed in loss of consciousness time or intubation time. The succinylcholine group tended to show better intubation conditions, but no significant difference was observed. None of the patients complained awareness of the intubation procedure or had respiratory difficulty during a postoperative interview. CONCLUSIONS: The modified RSI with rocuronium showed shorter intubation sequence, acceptable intubation conditions, and a similar level of complications compared to those of conventional RSI with succinylcholine.
Androstanols ; Apnea ; Complementary Therapies ; Fentanyl ; Humans ; Intubation ; Muscle Relaxation ; Muscles ; Neuromuscular Nondepolarizing Agents ; Propofol ; Prospective Studies ; Succinylcholine ; Unconsciousness

BACKGROUND: Recently, balanced anesthesia (BA: halogenated volatile anesthetics + remifentanil) has been useful for abdominal surgery. The authors therefore performed a retrospective study about the difference in the dose of vasoactive drugs and rocuronium according to the general anesthesia type. METHODS: BA was compared with inhalational anesthesia (IA: halogenated volatile anesthetics + N2O) and total intravenous anesthesia (TIVA: propofol + remifentanil). The records of a total of 415 patients (IA : TIVA : BA = 126 : 157 : 132) who received open gastrectomy between 2004 to 2010 were analyzed. The types of vasoactive drugs and dosage as well as infusion time were calculated. The total amounts of vasoactive drugs were scored by two different methods. Infusion drugs were scored as 30 points, whereas bolus drugs were scored as 5 points. Drug score is the total sum of each score, where each drug score point split either into Plus or Minus. Plus means raising the blood pressure whereas Minus means the opposite. For rocuronium dosage, a total of 286 patients (IA : TIVA : BA = 89 : 78 : 119) who met the criteria were enrolled, and this formula was used (total rocuronium/weight/time, microg/kg/hr). RESULTS: The BA group showed a lower (P = 0.01) Minus score (1.8 +/- 4.0) compared to the IA group (3.6 +/- 5.2). Less amount of rocuronium (P = 0.001) was administered in the BA (327 +/- 72 microg/kg/hr), compared to the IA (368 +/- 93 microg/kg/hr) and TIVA (356 +/- 81 microg/kg/hr). CONCLUSIONS: BA seems to require less hypotensive agent and rocuronium compared with IA and TIVA for open gastrectomy. But, well-designed prospective studies are required.
Androstanols ; Anesthesia ; Anesthesia, General ; Anesthesia, Intravenous ; Anesthetics ; Balanced Anesthesia ; Blood Pressure ; Gastrectomy ; Humans ; Piperidines ; Propofol ; Retrospective Studies

BACKGROUND: Although cisatracurium has many advantages in anesthetic practices, the best choice of a nondepolarizing neuromuscular blocking agent that can replace succinylcholine is rocuronium. However, it is reported that remifentanil with propofol might provide reliable intubating condition, even without a neuromuscular blocking agent; therefore, it might improve the intubating condition with cisatracurium. This study examined intubating conditions after administering rocuronium or cisatracurium in a rapid sequence induction with remifentanil-propofol. METHODS: Fifty two ASA physical status 1 or 2 adult patients scheduled for an elective surgery were enrolled in a randomized double-blinded trial. Anesthesia was induced in all patients with propofol 2.0 mg/kg and remifentanil 0.5 microgram/kg, administered over 60 seconds. Rocuronium 0.9 mg/kg (3 x ED95, R group, n = 23) or cisatracurium 0.15 mg/kg (3 x ED95, C group, n = 29) was administered after the induction sequence. Laryngoscopy was attempted when the anesthesiologist thought it was 90 seconds after drug administration and appropriate time for intubation. The examiner, another anesthesiologist, recorded the exact time to intubation and suppression of maximal T1 on TOF. The intubating condition was assessed by the first anesthesiologist, as excellent, good, poor or not possible. RESULTS: The best time to laryngoscopy was predicted by measuring TOF and was found to be significantly longer in the C group (197 +/- 53 s) than in the R group (102 +/- 49 s) (P value < 0.05). However, time to larygoscopy, intubating condition during the laryngoscopy, and hemodynamic changes after intubation was similar in both groups. CONCLUSIONS: Despite fundamentally slower onset time, cisatracurium can provide quite good intubating conditions, which were comparable to those achieved with equipotent doses of rocuronium, which is more expensive in anesthesia inducted with remifentanil and propofol.
Adult ; Androstanols ; Anesthesia ; Atracurium ; Hemodynamics ; Humans ; Intubation ; Laryngoscopy ; Neuromuscular Blockade ; Piperidines ; Propofol ; Succinylcholine

BACKGROUND: To analyze how lidocaine 40 mg mixed prevents injection pain of propofol affects the onset time of rocuronium, tracheal intubating conditions and intubation related hemodynamic changes. METHODS: This study consisted of 70 patients with an American Society of Anesthesiologists (ASA) physical status class 1 or 2 for general anesthesia. All the patients were randomly allocated into two groups: propofol 2 mg/kg plus normal saline 2 ml (Group C) and propofol 2 mg/kg plus 2% lidocaine 40 mg (Group L). Each group was administrated intravenously during induction and the patient was intubated 1 minute after an injection of 0.6 mg/kg of rocuronium. The time at disappearance of the first twitch and intubation scores were recorded. Also, blood pressure and heart rate were measured at the baseline, after intravenous injection of propofol, before intubation, and at 0, 1, 2, 3 and 5 minutes after intubation. RESULTS: There were no significant differences between group C and L (P > 0.05). CONCLUSIONS: 40 mg of lidocaine mixed with propofol to prevent injection pain did not affect the onset time of rocuronium, intubating conditions and intubation related hemodynamic changes.
Androstanols ; Anesthesia, General ; Blood Pressure ; Heart Rate ; Hemodynamics ; Humans ; Injections, Intravenous ; Intubation ; Lidocaine ; Neuromuscular Blockade ; Propofol

BACKGROUND: Pain on injection of rocuronium is a common clinical problem. We compared the efficacy of lidocaine, ketorolac, and the 2 in combination as pretreatment for the prevention of rocuronium-induced withdrawal movement. METHODS: For this prospective, randomized, placebo-controlled, double-blind study a total of 140 patients were randomly allocated to one of 4 treatment groups to receive intravenously placebo (saline), lidocaine (20 mg), ketorolac (10 mg), or both (n = 35 for each group), with venous occlusion. The tourniquet was released after 2 min and anesthesia was performed using 5 mg/kg thiopental sodium followed by 0.6 mg/kg rocuronium. The withdrawal response was graded on a 4-point scale in a double-blind manner. RESULTS: The overall incidence of withdrawal movements after rocuronium was 34.3% with lidocaine (P = 0.001), 40% with ketorolac (P = 0.004), and 8.6% with both (P < 0.001), compared with 74.3% with placebo. There was a significantly lower incidence of withdrawal movements in patients receiving the lidocaine/ketorolac combination than in those receiving lidocaine or ketorolac alone (P = 0.009 and 0.002, respectively). The incidence of moderate to severe withdrawal movements was 14.3% with lidocaine, 17.2% with ketorolac, and 2.9% with lidocaine/ketorolac combination, as compared to 45.7% with the placebo. There was no significant difference in withdrawal movement between the lidocaine group and the ketorolac group. CONCLUSIONS: Ketorolac pretreatment had an effect comparable to that of lidocaine in attenuating rocuronium-induced withdrawal movements and the lidocaine/ketorolac combination pretreatment, compared with lidocaine or ketorolac alone, effectively reduced withdrawal movements during rocuronium injection.
Androstanols ; Anesthesia ; Double-Blind Method ; Humans ; Incidence ; Ketorolac ; Lidocaine ; Prospective Studies ; Thiopental ; Tourniquets