Post-operative residual neuromuscular blockade after the administration of a single intubating dose of intermediate-acting non-depolarising neuromuscular blocking agent in adult elective surgical procedures

Objectives: Post-operative residual neuromuscular blockade may result in life-threatening conditions if not properly managed making it a common and significant concern among anaesthesiologists. Among adult elective surgeries requiring single intubating dose of intermediate-acting non-depolarising neuromuscular blocking agent, the study determined the incidence and risk factors associated with post-operative residual neuromuscular blockade during early post-operative period. Materials and Methods: A prospective, open-labelled, non-randomised observational study conducted in an operating room and post-anaesthesia care unit. A total of 175 ASA-PS Class I and II patients admitted in the surgical wards scheduled for elective surgical operation and were administered of a single intubating dose of intravenous intermediate-acting non-depolarising neuromuscular blocking drug. The train-of-four (TOF) method of peripheral nerve stimulation detects the presence of post-operative residual neuromuscular blockade. Results: A significant post-operative residual paralysis was identified in specific age groups (26–35, 46–55 and 56–65), in surgical procedures in the orthopaedic service, and among patients who were given a reversal agent. Residual neuromuscular blockade is still present even if the interval between the last dose of muscle relaxant and the measurement of TOF ratio at the post-anaesthesia care unit was long, however, less than that observed in short interval surgeries. Conclusion: Clinical importance of residual neuromuscular blockade is still evident up to the present time and the present study recommends routine monitoring of neuromuscular blockade and pharmacologic antagonism in the reversal of non-depolarising neuromuscular blocking drugs.

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Preclinical Pharmacology in the Rhesus Monkey of CW 1759-50, a New Ultra-short Acting Nondepolarizing Neuromuscular Blocking Agent, Degraded and Antagonized by L-Cysteine

Anesthesiology ◽

10.1097/aln.0000000000002408 ◽

2018 ◽

Vol 129 (5) ◽

pp. 970-988 ◽

Cited By ~ 2

Author(s):

John J. Savarese ◽

Hiroshi Sunaga ◽

Jeff D. McGilvra ◽

Matthew R. Belmont ◽

Matthew T. Murrell ◽

...

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Neuromuscular Blockade ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Duration Of Action ◽

Short Acting ◽

Circulatory Effects

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Structure–activity studies were performed to identify a new neuromuscular blocking agent retaining the ultra-short acting characteristics of gantacurium, including degradation and reversal by l-cysteine, but lacking its histaminoid properties in man. CW 1759-50 has emerged from this program. Methods Adduction of CW 1759-50 with l-cysteine was studied by high-performance liquid chromatography and mass spectrometry. Institutional Animal Care and Use Committee–approved comparisons of CW 1759-50 to gantacurium were performed in rhesus monkeys. ED95 for neuromuscular blockade was established. Spontaneous recovery was compared to reversal by l-cysteine in paired studies of boluses or infusions. In addition, changes in mean arterial pressure and heart rate after very large doses of 15 to 60 × ED95 were compared. Results The half-time of adduction of l-cysteine to CW 1759-50 in vitro was 2.3 min. The ED95 of CW 1759-50 was 0.069 ± 0.02 mg/kg; ED95 of gantacurium was 0.081 ± 0.05 mg/kg (P = 0.006). Duration of action (recovery to 95% twitch height after 98 to 99% blockade) was as follows: CW 1759-50, 8.2 ± 1.5 min; and gantacurium, 7.4 ± 1.9 min; (n = 8 and 9, P = 0.355). Administration of l-cysteine (30 mg/kg) shortened recovery (i.e., induced reversal) from CW 1759-50 after boluses or infusions (P always less than 0.0001). Recovery intervals (5 to 95% twitch) ranged from 6.1 to 6.7 min (and did not differ significantly) after boluses of 0.10 to 0.50 mg/kg, as well as control infusions (P = 0.426 by analysis of variance). Dose ratios comparing changes of 30% in mean arterial pressure or heart rate to ED95 for neuromuscular blockade (ED 30% Δ [mean arterial pressure or heart rate]/ED95) were higher for CW 1759-50 than for gantacurium. Conclusions CW 1759-50, similar to gantacurium, is an ultra-short acting neuromuscular blocking agent, antagonized by l-cysteine, in the monkey. The circulatory effects, however, are much reduced in comparison with gantacurium, suggesting a trial in humans.

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The Clinical Neuromuscular Pharmacology of 51W89 in Patients Receiving Nitrous Oxide/Opioid/Barbiturate Anesthesia

Anesthesiology ◽

10.1097/00000542-199505000-00008 ◽

1995 ◽

Vol 82 (5) ◽

pp. 1139-1145 ◽

Cited By ~ 106

Author(s):

Matthew R. Belmont ◽

Cynthia A. Lien ◽

Steve Quessy ◽

Martha M. Abou-Donia ◽

Amy Abalos ◽

...

Keyword(s):

Nitrous Oxide ◽

Surgical Procedures ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Blocking Effect ◽

Preclinical Studies ◽

Physical Status ◽

Elective Surgical Procedures ◽

Recovery Index

Background Atracurium is a mixture of ten stereoisomers. 51W89, one of these isomers, is a potent nondepolarizing intermediate-duration neuromuscular blocking agent. Preclinical studies have shown 51W89 to be significantly more potent than atracurium but with a similar neuromuscular blocking profile. This study was undertaken to establish the neuromuscular blocking potency and pharmacodynamics of 51W89 in patients undergoing elective surgical procedures. Methods Ninety-nine ASA physical status 1 or 2 patients undergoing elective surgical procedures under nitrous oxide/opioid/barbiturate anesthesia were studied. The neuromuscular blocking effect of 51W89 was assessed after administration of bolus doses from 0.015 to 0.4 mg/kg, as well as during and after continuous infusions from 11 to 249 min in length. Results The calculated ED95 for inhibition of adductor pollicis twitch evoked at 0.15 Hz was 0.048 mg/kg. At 0.10 mg/kg, maximum block developed within 5.2 +/- 0.3 min, and recovery to 95% twitch height occurred 64.4 +/- 3.9 min after injection. At 0.4 mg/kg, onset was 1.9 +/- 0.1 min, and 95% recovery developed within 121.0 +/- 5.9 min. Comparative recovery indexes from 5% to 95% or from 25% to 75% twitch heights did not differ significantly among all dosage groups from 0.1 to 0.4 mg/kg (means ranged from 29.6 to 32.3 min and from 12.6 to 14.3 min, respectively). The average infusion rate necessary to maintain approximately 95% twitch suppression was 1.35 micrograms/kg/min. Recovery indexes from infusions were 5-95% 33.2 +/- 1.8 min and 25-75% 15.0 +/- 0.6 min, not differing significantly from recovery indexes from single bolus doses. Twenty-five patients received neostigmine (0.06 mg/kg) with atropine (0.03 mg/kg) at twitch height recovery of between 6% and 21%. Antagonism to 95% control twitch height developed within 6.8 +/- 0.3 min, and the neostigmine-accelerated 25-75% recovery index was 2.8 +/- 0.2 min. Conclusions 51W89 is a potent nondepolarizing neuromuscular blocking agent that shows noncumulative intermediate-duration neuromuscular blocking pharmacodynamics.

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Response to Pancuronium after Loss of Atracurium-Induced Neuromuscular Blockade

Annals of Pharmacotherapy ◽

10.1177/106002809302700707 ◽

1993 ◽

Vol 27 (7-8) ◽

pp. 862-865 ◽

Cited By ~ 3

Author(s):

Karl J. Kelly ◽

Diann M. Clarens ◽

Philip R. Kohls ◽

Avi Nahum ◽

Kyle Vance-Bryan

Keyword(s):

Neuromuscular Blockade ◽

Infusion Rate ◽

Respiratory Control ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Constant Infusion ◽

Cross Tolerance ◽

Standard Dosage ◽

Airway Pressures

OBJECTIVE: To describe a previously unreported event in which a patient became refractory to atracurium-induced neuromuscular blockade, but subsequently was adequately paralyzed with a standard dosage of pancuronium. CASE SUMMARY: A previously healthy 17-year-old woman who sustained multiple trauma developed tolerance to an atracurium infusion she was receiving while undergoing mechanical ventilation. On day 3 of neuromuscular blockade, she became unresponsive to atracurium as evidenced by excessive physical movement, increased peak airway pressures, and overbreathing assist control ventilation. Repeat boluses and increases in the atracurium infusion rate to a maximum of 1.27 mg/kg/h failed to provide a desired clinical response. A bolus dose of pancuronium 0.15 mg/kg was administered and the constant infusion was then changed to pancuronium 0.078 mg/kg/h. Within minutes, decreased respirations, peak airway pressures, and agitation were noted. The pancuronium infusion rate was then tapered to 0.045 mg/kg/h over 72 hours and continued to maintain adequate neuromuscular blockade. DISCUSSION: Potential pharmacokinetic and pharmacodynamic causes of loss of neuromuscular blockade in this patient are postulated. Possible explanations for loss of neuromuscular blockade include increased degradation of atracurium and/or a change in acetylcholine receptor physiology. CONCLUSIONS: The development of resistance to a specific neuromuscular blocking agent in the intensive care setting does not necessarily imply cross-tolerance or resistance to alternative agents. Also, loss of respiratory control by one neuromuscular blocking agent may be overcome by changing agents.

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The availability and free use of sugammadex affects the choice of the neuromuscular blocking agent (NMBA) and the cost of neuromuscular blockade in general anaesthesia

10.26226/morressier.57108e2bd462b80290b49a43 ◽

2016 ◽

Author(s):

Elissavet Ypsilanti

Keyword(s):

General Anaesthesia ◽

Neuromuscular Blockade ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

The Cost

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Efek Pemberian Magnesium Sulfat 45 Mg/kgBB terhadap Kualitas Tindakan Intubasi Endotrakeal Tanpa Obat Pelumpuh Otot dan Perubahan Respons Hemodinamik

Jurnal Anestesi Perioperatif ◽

10.15851/jap.v7n1.1590 ◽

2019 ◽

Vol 7 (1) ◽

pp. 48-57

Author(s):

Fatima Fatima ◽

Erwin Pradian ◽

Dedi Fitri Yadi

Keyword(s):

Endotracheal Intubation ◽

Surgical Procedures ◽

Magnesium Sulphate ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Neuromuscular Blocking Agent ◽

Neuromuscular Blocking Agents ◽

Chi Square ◽

Blocking Agents

Intubasi endotrakeal merupakan tindakan berisiko tinggi yang menghasilkan stimulasi adrenergik. Intubasi endotrakeal menggunakan obat pelumpuh otot sebagai standar baku dapat menimbulkan efek samping berupa reaksi anafilaksis dan rekurisasi pascabedah. Intubasi endotrakeal tanpa obat pelumpuh otot ditujukan untuk prosedur pembedahan yang singkat, membutuhkan identifikasi saraf, dan terdapat kontraindikasi pemberian obat pelumpuh otot. Tujuan penelitian ini mengkaji pemberian magnesium sulfat 45 mg/kgBB terhadap kualitas intubasi dan respons hemodinamik pada tindakan intubasi endotrakeal tanpa obat pelumpuh otot. Penelitian ini merupakan penelitian eksperimental secara acak buta ganda yang dilakukan secara prospektif terhadap 42 subjek penelitian yang menjalani prosedur pembedahan dengan anestesi umum di Rumah Sakit Umum Pusat Dr. Hasan Sadikin, Bandung pada bulan April–Juli 2018. Pada penelitian ini, data numerik diuji dengan uji t tidak berpasangan, sedangkan data kategorik diuji dengan uji chi-square dan Mann Whitney. Hasil penelitian menunjukkan kualitas intubasi endotrakeal tanpa obat pelumpuh otot lebih baik dengan disertai penurunan respons hemodinamik pada kelompok yang diberikan magnesium sulfat 45 mg/kgBB dibanding dengan kelompok kontrol (p<0,05). Simpulan, pemberian magnesium sulfat 45 mg/kgBB meningkatkan kualitas tindakan intubasi endotrakeal tanpa obat pelumpuh otot yang dinilai menggunakan skor Copenhagen dan menurunkan respons hemodinamik pada tindakan intubasi endotrakeal tanpa obat pelumpuhotot.Effect of 45 mg/kgBW Magnesium Sulphate on Quality of Endotracheal Intubation without Neuromuscular Blocking Agents and Change in Hemodynamic ResponsesEndotracheal intubation is a high-risk procedure that can stimulate adrenergic response. Neuromuscular blocking agent is used to facilitate endotracheal intubation but it has undesirable effects such as anaphylactic reaction and postoperative recurarization. This technique is indicated for short surgical procedures, requires nerve identification, and is contraindicated for neuromuscular blocking agent. The purpose of this study was to review the effect of 45 mg/kgBW magnesium sulphate to the quality of intubation and hemodynamic responses in endotracheal intubation without neuromuscular blocking agent. This was a prospective double blind experimental study conducted on 42 research subjects underwent surgical procedures under general anesthesia in Dr. Hasan Sadikin General Hospital, Bandung in the period of April–July 2018. In this study, numerical data were tested by unpaired t test. Categorical data were tested by chi-square and Mann Whitney tests. The results showed that the quality of endotracheal intubation without neuromuscular blocking agent improved with minimum hemodynamic changes in the group receiving 45 mg/kgBW magnesium sulphate (p<0.05). It is concluded that 45 mg/kgBW magnesium sulphate improves intubating quality assessed using Copenhagen score and decreases hemodynamic responses to endotracheal intubation without neuromuscular blocking agents.

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Continuous Infusions of Muscle Relaxants — Why and How

Anaesthesia and Intensive Care ◽

10.1177/0310057x8701500111 ◽

1987 ◽

Vol 15 (1) ◽

pp. 83-89 ◽

Cited By ~ 6

Author(s):

G. H. Beemer

Keyword(s):

Continuous Infusion ◽

Neuromuscular Blockade ◽

Accurate Method ◽

Blocking Agent ◽

Neuromuscular Blocking ◽

Large Individual ◽

Variable Rate ◽

Pharmacokinetics And Pharmacodynamics ◽

Residual Neuromuscular Blockade ◽

Precise Degree

The degree of neuromuscular blockade that occurs in an individual patient following the administration of competitive neuromuscular blocking agents cannot be accurately predicted because of the large individual variation in the pharmacokinetics and pharmacodynamics of these agents. Without monitoring of the neuromuscular blockade, this unpredictability predisposes to the occurrence of residual curarisation with its potentially lethal consequences. Variable rate continuous infusion of a short-acting competitive neuromuscular blocking agent with monitoring of the neuromuscular blockade is a flexible and accurate method for maintaining a precise degree of neuromuscular blockade during prolonged surgical procedures which ensures reliable reversability of the residual neuromuscular blockade. A system for the continuous infusion of atracurium with manual monitoring of the neuromuscular blockade is described, together with the results of a study demonstrating its efficacy.

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