The Influence of Mild Hypothermia on the Pharmacokinetics and Time Course of Action of Neostigmine in Anesthetized Volunteers

2002 ◽  
Vol 97 (1) ◽  
pp. 90-95 ◽  
Author(s):  
Tom Heier ◽  
David Clough ◽  
Peter M. C. Wright ◽  
Manohar L. Sharma ◽  
Daniel I. Sessler ◽  
...  
Keyword(s):  
Time Course ◽  
Mechanical Response ◽  
Mild Hypothermia ◽  
Neuromuscular Block ◽  
Onset Time ◽  
Volume Of Distribution ◽  
Maximum Effect ◽  
Surface Cooling ◽  
Duration Of Action ◽  
Course Of Action

Background The pharmacokinetics, maximum effect, and time course of action of neostigmine were studied in seven human volunteers. Methods Each volunteer was studied twice, during both normothermia and hypothermia. Anesthesia was induced with 30 microg/kg alfentanil and 3 mg/kg propofol, and was maintained with 60-70% nitrous oxide and 0.7-0.9% isoflurane. The mechanical response of the adductor pollicis to train-of-four stimulation of the ulnar nerve was recorded, and central body temperature maintained stable at either less than 34.5 degrees C or greater than 36.5 degrees C by surface cooling or warming. Before neostigmine administration, a stable 5% twitch height was obtained by an infusion of vecuronium, and the infusion rate remained unchanged thereafter. Neostigmine, 70 microg/kg, was then infused over 2 min, and blood samples for estimation of neostigmine concentrations were collected at intervals for 240 min. Results With hypothermia, the central volume of distribution of neostigmine decreased by 38%, and onset time of maximum effect increased (4.6 vs. 5.6 min). Hypothermia did not change the clearance (696 ml/min), maximum effect, or duration of action of neostigmine. Conclusions The efficacy of neostigmine as an antagonist of vecuronium-induced neuromuscular block is not altered by mild hypothermia.

Repeated Doses of Rocuronium Bromide Administered to Cirrhotic and Control Patients Receiving Isoflurane

1996 ◽  
Vol 84 (5) ◽  
pp. 1092-1100 ◽  
Author(s):  
Frederique S. Servin ◽  
Elisabeth Lavaut ◽  
Ursula Kleef ◽  
Jean Marie Desmonts
Keyword(s):  
Initial Dose ◽  
Time Course ◽  
Volume Of Distribution ◽  
Individual Variability ◽  
Pharmacokinetic Analysis ◽  
Response Curves ◽  
Duration Of Action ◽  
Control Subjects ◽  
Course Of Action ◽  
Cirrhotic Patients

Background Steroid muscle relaxants often display pharmacodynamic changes in patients with cirrhosis because of alterations in elimination processes. Rocuronium is a new steroid muscle relaxant possibly eliminated through the liver. This study was designed to compare rocuronium pharmacodynamics and pharmacokinetics in cirrhotic and healthy patients. Methods Rocuronium was administered to 26 cirrhotic patients and 24 control subjects anesthetized with isoflurane for an elective procedure. Patients were randomly allocated to received an initial dose of rocuronium: 120, 180, 250, or 300 micrograms.kg-1. Dose-response curves were established, and ED50 was calculated. Preselected maintenance doses (75, 150, or 225 micrograms.kg-1) were administered at 25% recovery of twitch height to compare clinical duration of action. At the end of the procedure, relaxation was reversed in half of the patients, and the time course of recovery was compared in the two groups. Blood samples drawn during the procedure and after the last maintenance dose allowed pharmacokinetic analysis in six cirrhotic patients and six control subjects. Results ED50 of the initial dose was 144 micrograms.kg-1 in cirrhotic patients and 60 micrograms.kg-1 in control subjects, related to a higher initial volume of distribution (cirrhotic 78.5 +/- 31.7 ml.kg-1, control 29.8 +/- 17.3 ml.kg-1). Time from complementary dose to 25% recovery was longer in cirrhotic patients (41.0 +/- 20.7 min vs 30.2 +/- 9.7 min), but time course of action during maintenance was not statistically different in the two groups. In cirrhotic patients receiving five maintenance doses or more, prolongation of the duration of action with successive maintenance doses could be statistically demonstrated. Spontaneous recovery was delayed in cirrhotic patients, because of impaired elimination processes: greater volume of distribution at steady-state (264 +/- 92 vs. 151 +/- 59 ml.kg-1); trend toward a lower clearance (189 +/- 60 vs. 296 +/- 169 ml.min-1). Conclusions Rocuronium pharmacodynamics are moderately altered by cirrhosis, possible because of pharmacokinetic alterations. Individual variability in response to rocuronium is great, and dosage should be carefully titrated to that required.

scholarly journals Neuromuscular block in patients 80 years and older: a prospective, controlled study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Denis Schmartz ◽  
Raouf Sghaier ◽  
Paul Bernard ◽  
Jean François Fils ◽  
Thomas Fuchs-Buder
Keyword(s):  
Time Course ◽  
Neuromuscular Block ◽  
Demographic Data ◽  
Onset Time ◽  
Rapid Onset ◽  
Controlled Study ◽  
Younger Adults ◽  
Number Of Patients ◽  
Long Acting ◽  
Prospective Controlled Study

Abstract Background An increasing number of patients older than 80 years are undergoing anesthesia, but little information is available regarding pharmacodynamic effects of myorelaxants in this population. This study aims to compare the time course of rocuronium neuromuscular block in patients ≥ 80 years with those of younger adults. Methods Under total intravenous anesthesia with propofol and sufentanil, time course of a bolus of rocuronium 0.6 mg/kg neuromuscular block was assessed with acceleromyography in patients ≥ 80 and in patients 20–50 years old. Onset time, clinical duration, duration until 90% and 100% recovery of baseline were determined. Results Data from 32 patients were analyzed, 16 were ≥ 80 years and 16 were 20–50 years old. Demographic data are shown in Table 1. In the group ≥ 80, onset time was 190 s ± 46 s compared to 123 s ± 40 s in the group 20–50, P < 0.001 and the clinical duration was 52 [48–69.5] min and 36 [34–41] min, respectively, P < 0.001. Duration to 90% recovery of baseline was 77.5 [71–88.5] min and duration to 100% recovery of baseline was 91.2 [82.2–98] min in patients ≥ 80 years and the corresponding values in the patients 20–50 years old were 53.5 [49–55.5] min and 59.5 [56.5–70.25] min, respectively, P < 0.001. Conclusion Compared to younger adults rocuronium shifted in patients ≥ 80 years from a rapid onset, intermediate acting compound to a slower onset, long-acting compound. Trial registration ClinicalTrials.gov identifier: NCT03551652 (29/05/2018).

Dose-Response of Rocuronium Bromide in Children Anesthetized with Propofol 

1997 ◽  
Vol 87 (6) ◽  
pp. 1368-1372 ◽  
Author(s):  
Rex L. Woolf ◽  
Mark W. Crawford ◽  
Shu May Choo
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Neuromuscular Block ◽  
Linear Regression Analysis ◽  
Rapid Onset ◽  
Rocuronium Bromide ◽  
Response Data ◽  
Course Of Action ◽  
Recovery Profile ◽  
Supramaximal Stimulation

Background The aim of this study was to determine the potency of rocuronium during propofol/fentanyl/N2O anesthesia in children and to compare the time course of action of rocuronium at doses of two and three times the ED95 with that of succinylcholine. Methods Rocuronium (120, 160, 200, or 240 microg/kg) was administered to 48 children aged 2-10 yr. Neuromuscular block was assessed by monitoring the electromyographic response of the adductor digiti minimi to supramaximal stimulation of the ulnar nerve at 2 Hz for 2 s every 10 s. Potency was determined by log-probit transformation and least-squares linear regression analysis of dose and response. In a second group of 30 children, the onset and recovery profile of rocuronium at doses of two and three times the ED95 was compared with that of succinylcholine (2 mg/kg). Results Values for ED50 and ED95 were 210 +/- 24 and 404 +/- 135 microg/kg, respectively. The time to 90% neuromuscular block after 1.2 mg/kg rocuronium (three times the ED95), 33 +/- 5 s (mean +/- SD), did not differ significantly from that after succinylcholine, at 30 +/- 7 s; however, both were significantly less than that after 0.8 mg/kg rocuronium, 46 +/- 8 s (P &lt; 0.05). The time to 25% recovery from 1.2 microg/kg rocuronium, 41 +/- 13 min, was approximately 50% greater than that after 0.8 mg/kg, at 27 +/- 6 min (P &lt; 0.001), and eight times greater than that after succinylcholine, at 5.2 +/- 1.9 min (P &lt; 0.001). Conclusions Both 1.2 mg/kg rocuronium (three times the ED95) and 2 mg/kg succinylcholine provide 90% neuromuscular block within 45 s in 95% of children. The present dose-response data support the use of rocuronium at a dose of 1.2 mg/kg when rapid onset and intermediate-duration neuromuscular block are needed in children.

ORG 9487 Neuromuscular Block at the Adductor Pollicis and the Laryngeal Adductor Muscles in Humans 

1997 ◽  
Vol 86 (6) ◽  
pp. 1300-1305 ◽  
Author(s):  
Bertrand Debaene ◽  
Thomas Lieutaud ◽  
Valerie Billard ◽  
Claude Meistelman
Keyword(s):  
Neuromuscular Block ◽  
Onset Time ◽  
Rapid Onset ◽  
Adductor Pollicis ◽  
Vocal Cords ◽  
Onset Of Action ◽  
Duration Of Action ◽  
Adductor Pollicis Muscle ◽  
Org 9487 ◽  
Adductor Muscles

Background ORG 9487 is a new steroidal nondepolarizing muscle relaxant with a rapid onset of action. This study was designed to determine the neuromuscular blocking profile of ORG 9487 at the adductor muscles of the larynx and the adductor pollicis. Methods In 30 adults, anesthesia was induced with propofol (2-5 mg/kg) and fentanyl (2-3 microg/kg). After train-of-four stimulation, the block of the laryngeal adductor muscles was evaluated by measuring the pressure changes in the cuff of the tracheal tube placed between the vocal cords, and the force of the contraction of the adductor pollicis was measured with a force transducer. Patients were randomly allocated to receive ORG 9487 at intravenous bolus doses of 0.75, 1.5 or 2 mg/kg (n = 10 in each group). Results Time to peak effect was significantly shorter at the vocal cords than at the adductor pollicis muscle (P &lt; 0.001). Onset time at the vocal cords was 62 +/- 16 s, 62 +/- 13 s, and 52 +/- 14 s (mean +/- SD) after doses of 0.75, 1.5, and 2 mg/kg, respectively (not significant). Onset time at the adductor pollicis muscle was 126 +/- 33 s, 96 +/- 20 s, and 82 +/- 21 s after 0.75, 1.5, and 2 mg/kg doses, respectively (P &lt; 0.001). Maximum block was significantly less intense at the vocal cords than at the adductor pollicis muscle (69 +/- 15% vs. 94 +/- 4% after 0.75 mg/kg; 86 +/- 7% vs. 97 +/- 4% after 1.5 mg/kg; and 91 +/- 5% vs. 99 +/- 1% after 2 mg/kg). After 1.5 mg/kg duration to 25%, recovery was 3.7 +/- 2.2 min versus 10.2 +/- 2.5 min at the vocal cords and the adductor pollicis muscle, respectively, and 75% recovery occurred at 9.7 +/- 3.7 min at the vocal cords and at 18.3 +/- 5.2 min at the adductor pollicis muscle. Conclusions ORG 9487 has a rapid onset of action at the laryngeal adductor and the adductor pollicis muscles. Onset and duration of action are faster at the vocal cords than at the adductor pollicis muscle. However, the maximum block obtained at the laryngeal muscles was less than at the adductor pollicis, regardless of the dose of ORG 9487.

scholarly journals The Effect of Midazolam Pre-Medication on Rocuronium-Induced Neuromuscular Blockade

2002 ◽  
Vol 30 (3) ◽  
pp. 318-321 ◽  
Author(s):  
H Hepağuşlar ◽  
S Öztekin ◽  
Ö Mavioğlu ◽  
B Tuncali ◽  
Z Elar
Keyword(s):  
Neuromuscular Blockade ◽  
Time Course ◽  
Elective Surgery ◽  
Control Group ◽  
Duration Of Action ◽  
Sevoflurane Anaesthesia ◽  
Related Data ◽  
Course Of Action ◽  
Train Of Four ◽  
Neuromuscular Responses

We investigated the effect of midazolam pre-medication on rocuronium-induced neuromuscular blockade during sevoflurane anaesthesia. Twenty-two patients scheduled for elective surgery were randomly divided to receive either no pre-medication (control group) or pre-medication with 0.1 mg/kg midazolam intramuscularly (midazolam group). Anaesthesia was induced with fentanyl and propofol, and maintained with sevoflurane and nitrous oxide in oxygen. Neuromuscular responses were monitored using acceleromyography. The onset and clinical duration of action, time to recovery of first twitch of train-of-four (TOF) response to 75% of control, recovery index and time for TOF recovery to 25% and 50% were recorded. Patient-related data were similar in both groups. The parameters recorded were not significantly different between the groups. Midazolam pre-medication does not influence the time-course of action of rocuronium during sevoflurane anaesthesia.

Temporal Relation between Acoustic and Force Responses at the Adductor Pollicis during Nondepolarizing Neuromuscular Block

2000 ◽  
Vol 93 (3) ◽  
pp. 646-652 ◽  
Author(s):  
François Bellemare ◽  
Jacques Couture ◽  
François Donati ◽  
Benoît Plaud
Keyword(s):  
Time Course ◽  
Mechanical Response ◽  
Elective Surgery ◽  
Neuromuscular Block ◽  
Adductor Pollicis ◽  
Adductor Pollicis Muscle ◽  
Palmar Surface ◽  
Force Relaxation ◽  
Train Of Four ◽  
Acoustic Myography

Background Contracting muscle emits sounds. The purpose of this study was to compare the time course of muscular paralysis at the adductor pollicis muscle (AP) with use of acoustic myography and mechanomyography. Methods Thirteen elective surgery patients, American Society of Anesthesiologists physical status I, received rocuronium (0.6 mg/kg intravenously) as a bolus dose during general anesthesia. Force of AP was measured with use of a strain gauge, and sounds were recorded simultaneously with use of a small condenser microphone fixed on the palmar surface of the hand over the AP. Supramaximal stimulation was applied to the ulnar nerve at 0.1 Hz for 45-60 min. In seven patients, the response to train-of-four stimulation was also recorded during recovery. Results Force and sounds both were equally sensitive in measuring maximum block. The relation between sound and force was curvilinear, with good agreement near 0 and 100% and acoustic response exceeding mechanical response at intermediate levels of block. The acoustic signal had a slower onset and a faster recovery than the force response. The fade response of sound to train-of-four stimulation also recovered faster than that of force. Conclusion Acoustic myography is an alternative method to monitor muscular paralysis that is easy to set up and applicable to most superficial muscles. However, the time course of relaxation at AP using acoustic myography differs from the time course of force relaxation. Therefore, these two methods are not equivalent when applied to AP.

Geographic Regional Differences in Rocuronium Bromide Dose–Response Relation and Time Course of Action

2006 ◽  
Vol 104 (5) ◽  
pp. 950-953 ◽  
Author(s):  
Ashraf A. Dahaba ◽  
Seth I. Perelman ◽  
David M. Moskowitz ◽  
Henry L. Bennett ◽  
Aryeh Shander ◽  
...  
Keyword(s):  
Dose Response ◽  
Time Course ◽  
Neuromuscular Block ◽  
Chinese Patients ◽  
Ambient Conditions ◽  
Response Curves ◽  
Rocuronium Bromide ◽  
Duration Of Action ◽  
Significant Difference ◽  
Geographic Regions

Background Geographic location is not acknowledged as a stratifying factor that can directly affect drug potency, because drugs are still licensed with the same recommended dose for different geographic regions. The aim of the current study was to compare the potency and duration of action of rocuronium bromide in 54 patients in three countries with different life habits, diet, and ambient conditions, namely white Austrians, white North Americans, and Han Chinese in China. Methods Neuromuscular block of six consecutive 50-microg/kg rocuronium incremental doses followed by 300 microg/kg was evaluated using the Relaxometer mechanomyograph (Groningen University, Groningen, Holland). Dose-response curves were created using log-dose-probit transformation. The authors compared rocuronium bromide ED50, ED90, and ED95 (effective doses required for 50%, 90%, and 95% first twitch depression, respectively) as well as Dur25 and Dur0.8 (times from last incremental dose administration until 25% first twitch and 0.8 train-of-four ratio recovery, respectively) in patients of the three countries. Results Rocuronium ED50, ED90, and ED95 were significantly higher in Austrian patients (258 +/- 68, 530 +/- 159, and 598 +/- 189 microg/kg) and Chinese patients (201 +/- 59, 413 +/- 107, and 475 +/- 155 microg/kg) compared with American patients (148 +/- 48, 316 +/- 116, and 362 +/- 149 microg/kg, respectively). Dur25 and Dur0.8 were significantly shorter in Austrian patients (22.3 +/- 5.5 and 36.9 +/- 12.8 min) and Chinese patients (30.4 +/- 7.5 and 45.7 +/- 15.9 min) compared with American patients (36.7 +/- 8.5 and 56.2 +/- 16.7 min, respectively). Conclusions The authors demonstrated a significant difference in rocuronium potency and duration of action among patients in the three countries. Larger studies are required for determining dosage recommendations for different geographic regions.

The Magnitude and Time Course of Vecuronium Potentiation by Desflurane Versus Isoflurane 

1995 ◽  
Vol 82 (2) ◽  
pp. 404-411 ◽  
Author(s):  
Peter M.C. Wright ◽  
Paul Hart ◽  
Marie Lau ◽  
Ronald Brown ◽  
Manohar L. Sharma ◽  
...  
Keyword(s):  
Time Course ◽  
Bolus Dose ◽  
Response Times ◽  
Muscle Relaxants ◽  
Dose Requirement ◽  
Duration Of Action ◽  
Isoflurane Anesthesia ◽  
Course Of Action ◽  
Anesthetic Concentration ◽  
End Tidal

Background Preliminary studies suggest that desflurane and isoflurane potentiate the action of muscle relaxants equally. However, variability between subjects may confound these comparisons. A crossover study was performed in volunteers on the ability of desflurane and isoflurane to potentiate the neuromuscular effect of vecuronium, to influence its duration of action, and on the magnitude and time course of reversal of potentiation when anesthesia was withdrawn. Methods Adductor pollicis twitch tension was monitored in 16 volunteers given 1.25 MAC desflurane on one occasion, and 1.25 MAC isoflurane on another. In eight subjects, vecuronium bolus dose potency was determined using a two-dose dose-response technique; the vecuronium infusion dose requirement to achieve 85% twitch depression also was determined. Also in these subjects, the magnitude and time course of spontaneous neuromuscular recovery were determined when the anesthetic was withdrawn while maintaining a constant vecuronium infusion. In the other eight subjects, the time course of action of 100 micrograms/kg vecuronium was determined. Results Vecuronium's ED50 and infusion requirement to maintain 85% twitch depression were 20% less during desflurane, compared to isoflurane, anesthesia; vecuronium plasma clearance was similar during the two anesthetics. After 100 micrograms/kg vecuronium, onset was faster and recovery was longer during desflurane anesthesia. When the end-tidal anesthetic concentration was abruptly reduced from 1.25 to 0.75 MAC, twitch tension increased similarly (approximately 15% of control), and time for the twitch tension to reach 90% of the final change was similar (approximately 30 min) with both anesthetics. Decreasing anesthetic concentration from 0.75 to 0.25 MAC increased twitch tension by 46 +/- 10% and 25 +/- 7% of control (mean +/- SD, P &lt; 0.001) with desflurane and isoflurane, respectively; 90% response times for these changes were 31 +/- 10 min and 18 +/- 7 min (P &lt; 0.05), respectively. Conclusions Desflurane potentiates the effect of vecuronium approximately 20% more than does an equipotent dose of isoflurane.

scholarly journals Coagulation under Mild Hypothermia Assessed by Thromboelastometry

2021 ◽  
pp. 1-7
Author(s):  
Tobias Nitschke ◽  
Philipp Groene ◽  
Alice-Christin Acevedo ◽  
Tobias Kammerer ◽  
Simon T. Schäfer
Keyword(s):  
Mild Hypothermia ◽  
Onset Time ◽  
Rotational Thromboelastometry ◽  
Lysis Time ◽  
Sample Data ◽  
In Vivo Testing ◽  
Fibrinolytic Capacity ◽  
Clot Formation Time

<b><i>Introduction:</i></b> While previous studies have shown a significant impact of extreme hypo- and hyperthermia on coagulation, effects of much more frequently occurring perioperative mild hypothermia are largely unknown. This study therefore aimed to analyze the effects of mild hypothermia using rotational thromboelastometry in vitro. <b><i>Materials and Methods:</i></b> Twelve healthy volunteers were included in this study. Standard thromboelastometric tests (EXTEM, INTEM, FIBTEM) were used to evaluate coagulation in vitro at 39, 37, 35.5, 35, and 33°C. Beyond standard thromboelastometric tests, we also evaluated the effects of mild hypothermia on the TPA-test (ClotPro, Enicor GmbH, Munich, Germany), a new test which aims to detect fibrinolytic capacity by adding tissue plasminogen activator to the sample. Data are presented as the median with 25/75th percentiles. <b><i>Results:</i></b> Extrinsically activated coagulation (measured by EXTEM) showed a significant increase in clot formation time (CFT; 37°C: 90 s [81/105] vs. 35°C: 109 s [99/126]; <i>p</i> = 0.0002), while maximum clot firmness (MCF) was not significantly reduced. Intrinsically activated coagulation (measured by INTEM) also showed a significant increase in CFT (37°C: 80 s [72/88] vs. 35°C: 94 s [86/109]; <i>p</i> = 0.0002) without significant effects on MCF. Mild hypothermia significantly increased both the lysis onset time (136 s [132/151; 37°C] vs. 162 s [141/228; 35°C], <i>p</i> = 0.0223) and lysis time (208 s [184/297; 37°C] vs. 249 s [215/358; 35°C]; <i>p</i> = 0.0259). <b><i>Conclusion:</i></b> This demonstrates that even under mild hypothermia coagulation is significantly altered in vitro. Perioperative temperature monitoring and management are greatly important and can help to prevent mild hypothermia and its adverse effects. Further investigation and in vivo testing of coagulation under mild hypothermia is needed.

Sign in / Sign up

Export Citation Format

Share Document