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European Journal of Anaesthesiology May 2024Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines...
Extravascular injection of neuromuscular blocking drugs (NMBDs) can cause a neuromuscular block because of systemic absorption. Currently, there are no guidelines available on managing extravasation of NMBDs. This article reviews the available literature on extravasation of NMBDs. Medline and Embase databases were searched for studies concerning the paravenous or subcutaneous injection of NMBDs. Nine articles were included consisting of seven case reports, one case series and one clinical trial. Rocuronium was used as primary NMBD in nine cases, vecuronium in two cases and pancuronium in one case. Although there exists significant heterogeneity between the reported information in the included studies, the majority of the case reports describe a slower onset, with a median delay of 20 min and prolonged duration of the neuromuscular block. Nine patients had a residual neuromuscular block at the end of the surgery. Postoperative monitoring in the recovery room was prolonged (median time 4 h). Most studies suggest that the delay in NMBD onset and recovery is caused by the formation of a subcutaneous depot, from which the NMBD is slowly absorbed into the systemic circulation. According to the current literature, extravasation of NMBDs results in an unpredictable neuromuscular block. Strategies to prevent potentially harmful side effects, such as frequent train-of-four (TOF) monitoring, the use of NMBD reversal agents and prolonged length of stay in the postanaesthesia care unit (PACU), should be considered. This article suggests a clinical pathway that can be used after extravascular injection of NMBDs.
Topics: Humans; Neuromuscular Blockade; Rocuronium; Vecuronium Bromide; Delayed Emergence from Anesthesia; Monitoring, Intraoperative
PubMed: 38410855
DOI: 10.1097/EJA.0000000000001967 -
British Journal of Anaesthesia Mar 2024The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium...
The phenomena of residual curarisation and recurarisation after the use of long-acting non-depolarising neuromuscular blocking drugs such as tubocurarine and pancuronium were well recognised 60 years ago. But the incidence seemed to decline with the introduction of atracurium and vecuronium. However, recently there have been an increasing number of reports of residual and recurrent neuromuscular block. Some of these reports are a result of inappropriate doses of rocuronium, sugammadex or both, together with inadequate neuromuscular monitoring. We urge clinicians to review their practice to ensure the highest standards of clinical care when using neuromuscular blocking drugs and reversal agents. This includes the use of quantitative neuromuscular monitoring whenever neuromuscular blocking drugs are administered.
Topics: Humans; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Androstanols; Rocuronium; Vecuronium Bromide; Neuromuscular Blocking Agents
PubMed: 38135525
DOI: 10.1016/j.bja.2023.12.001 -
The Journal of Physiology Dec 2023The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed...
The role played by the transient receptor potential vanilloid 1 (TRPV1) channel on the thin fibre afferents evoking the exercise pressor reflex is controversial. To shed light on this controversy, we compared the exercise pressor reflex between newly developed TRPV1 , TRPV1 and TRPV1 rats. Carotid arterial injection of capsaicin (0.5 μg), evoked significant pressor responses in TRPV1 and TRPV1 rats, but not in TRPV1 rats. In acutely isolated dorsal root ganglion neurons innervating the gastrocnemius muscles, capsaicin evoked inward currents in neurons isolated from TRPV1 and TRPV1 rats but not in neurons isolated from TRPV1 rats. The reflex was evoked by stimulating the tibial nerve in decerebrated rats whose femoral artery was either freely perfused or occluded. We found no difference between the reflex in the three groups of rats regardless of the patency of the femoral artery. For example, the peak pressor responses to contraction in TRPV1 , TRPV1 and TRPV1 rats with patent femoral arteries averaged 17.1 ± 7.2, 18.9 ± 12.4 and 18.4 ± 8.6 mmHg, respectively. Stimulation of the tibial nerve after paralysis with pancuronium had no effect on arterial pressure, findings which indicated that the pressor responses to contraction were not caused by electrical stimulation of afferent tibial nerve axons. We also found that expression levels of acid-sensing ion channel 1 and endoperoxide 4 receptor in the L4 and 5 dorsal root ganglia were not upregulated in the TRPV1 rats. We conclude that TRPV1 is not needed to evoke the exercise pressor reflex in rats whose contracting muscles have either a patent or an occluded arterial blood supply. KEY POINTS: A reflex arising in contracting skeletal muscle contributes to the increases in arterial blood pressure, cardiac output and breathing evoked by exercise. The sensory arm of the reflex comprises both mechanoreceptors and metaboreceptors, of which the latter signals that blood flow to exercising muscle is not meeting its metabolic demand. The nature of the channel on the metaboreceptor sensing a mismatch between supply and demand is controversial; some believe that it is the transient receptor potential vanilloid 1 (TRPV1) channel. Using genetically engineered rats in which the TRPV1 channel is rendered non-functional, we have shown that it is not needed to evoke the metaboreflex.
Topics: Animals; Rats; Blood Pressure; Capsaicin; Femoral Artery; Muscle Contraction; Muscle, Skeletal; Rats, Sprague-Dawley; Reflex; Transient Receptor Potential Channels
PubMed: 37878364
DOI: 10.1113/JP285267 -
PloS One 2023Muscle relaxants are indispensable for surgical anesthesia. Early studies suggested that a classical non-depolarizing muscle relaxant pancuronium competitively binds to...
Muscle relaxants are indispensable for surgical anesthesia. Early studies suggested that a classical non-depolarizing muscle relaxant pancuronium competitively binds to the ligand binding site to block nicotinic acetylcholine receptors (nAChR). Our group recently showed that nAChR which has two distinct subunit combinations are expressed in zebrafish muscles, αβδε and αβδ, for which potencies of pancuronium are different. Taking advantage of the distinct potencies, we generated chimeras between two types of nAChRs and found that the extracellular ACh binding site is not associated with the pancuronium sensitivity. Furthermore, application of either 2 μM or 100 μM ACh in native αβδε or αβδ subunits yielded similar IC50 of pancuronium. These data suggest that pancuronium allosterically inhibits the activity of zebrafish nAChRs.
Topics: Animals; Pancuronium; Receptors, Nicotinic; Zebrafish; Muscles; Neuromuscular Blocking Agents
PubMed: 37824562
DOI: 10.1371/journal.pone.0292262 -
ACS Sensors Jul 2023Electrochemical detection methods are attractive for developing miniaturized, disposable, and portable sensors for molecular diagnostics. In this article, we present a...
Electrochemical detection methods are attractive for developing miniaturized, disposable, and portable sensors for molecular diagnostics. In this article, we present a cucurbit[7]uril-based chemosensor with an electrochemical signal readout for the micromolar detection of the muscle relaxant pancuronium bromide in buffer and human urine. This is possible through a competitive binding assay using a chemosensor ensemble consisting of cucurbit[7]uril as the host and an electrochemically active platinum(II) compound as the guest indicator. The electrochemical properties of the indicator are strongly modulated depending on the complexation state, a feature that is exploited to establish a functional chemosensor. Our design avoids cumbersome immobilization approaches on electrode surfaces, which are associated with practical and conceptual drawbacks. Moreover, it can be used with commercially available screen-printed electrodes that require minimal sample volume. The design principle presented here can be applied to other cucurbit[]uril-based chemosensors, providing an alternative to fluorescence-based assays.
Topics: Humans; Bridged-Ring Compounds; Imidazoles; Electrodes; Electrochemical Techniques
PubMed: 37339775
DOI: 10.1021/acssensors.3c00008 -
European Journal of Pharmaceutical... Aug 2023During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking...
Predictive stability, novel HPLC-MS analysis and semi-automatic compounding process for the emergency implementation of a production line of pancuronium in injectable solution.
During the early months of the COVID-19 pandemic, the international medical product supply chain was tight, causing breaks in the availability of neuromuscular blocking agents essential for the treatment of patients in intensive care units. The present study describes the pharmaceutical development of an injectable 2 mg/mL solution of pancuronium bromide (PC) in a very short lapse of time. The sterile solution was compounded into a good manufacturing practice grade A clean room, filtered (0.2 µm) and filled into 10 mL type I glass, manually sealed with bromobutyl rubber stoppers. A novel HPLC-MS stability indicating method for pancuronium quantification and its degradation product was developed and validated. This fast, sensitive and straightforward method was used to study the stability of the formulation using a semi-predictive method, enabling a very fast attribution of a temporary shelf-life, which was confirmed by a classic prospective stability study. The production line and the analytical tools set-up were performed in six weeks and the semi-predictive stability study was conducted in 90 days, allowing us to predict a shelf life, which was successfully confirmed by prospective study. In conclusion, using innovative methods, we were able to rapidly overcome the shortage of a critical drug.
Topics: Humans; Chromatography, High Pressure Liquid; Pancuronium; Prospective Studies; Pandemics; COVID-19; Drug Stability; Drug Compounding
PubMed: 37169099
DOI: 10.1016/j.ejps.2023.106464