| 1. |
- Jonsson, M., et al.
(author)
-
Neuromuscular blocking agents block carotid body neuronal nicotinic acetylcholine receptors
- 2004
-
In: European Journal of Pharmacology. - : Elsevier BV. - 0014-2999 .- 1879-0712. ; 497:2, s. 173-180
-
Journal article (peer-reviewed)abstract
- Neuromuscular blocking agents predominantly block muscle type nicotinic acetylcholine receptors as opposed to the neuronal type. However, there is growing evidence that neuromuscular blocking agents have affinity to some neuronal nicotinic acetylcholine receptors. The carotid body chemoreceptor as the essential oxygen-sensing cell, relies on cholinergic signalling. Atracurium and vecuronium impair carotid body chemoreceptor activity during hypoxia. Here, we characterize atracurium and vecuronium as antagonists at nicotinic receptors of the carotid body chemoreceptor. Isolated rabbit carotid body preparations with carotid sinus nerve were used, and chemoreceptor activities were recorded. There was a concentration-dependent reduction in the chemoreceptor responses to nicotine, with an IC50 to 50 µg nicotine of 3.64 and 1.64 µM and to 500 µg nicotine of 27.00 µM and 7.29 µM for atracurium and vecuronium, respectively. It is concluded that atracurium and vecuronium depress nicotine-induced chemoreceptor responses of the carotid body in a dose-dependent fashion. © 2004 Elsevier B.V. All rights reserved.
|
|
| 2. |
- Nielsen, Niklas, et al.
(author)
-
Target temperature management after out-of-hospital cardiac arrest-a randomized, parallel-group, assessor-blinded clinical trial-rationale and design
- 2012
-
In: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 541-548
-
Journal article (peer-reviewed)abstract
- Background Experimental animal studies and previous randomized trials suggest an improvement in mortality and neurologic function with induced hypothermia after cardiac arrest. International guidelines advocate the use of a target temperature management of 32 degrees C to 34 degrees C for 12 to 24 hours after resuscitation from out-of-hospital cardiac arrest. A systematic review indicates that the evidence for recommending this intervention is inconclusive, and the GRADE level of evidence is low. Previous trials were small, with high risk of bias, evaluated select populations, and did not treat hyperthermia in the control groups. The optimal target temperature management strategy is not known. less thanbrgreater than less thanbrgreater thanMethods The TTM trial is an investigator-initiated, international, randomized, parallel-group, and assessor-blinded clinical trial designed to enroll at least 850 adult, unconscious patients resuscitated after out-of-hospital cardiac arrest of a presumed cardiac cause. The patients will be randomized to a target temperature management of either 33 degrees C or 36 degrees C after return of spontaneous circulation. In both groups, the intervention will last 36 hours. The primary outcome is all-cause mortality at maximal follow-up. The main secondary outcomes are the composite outcome of all-cause mortality and poor neurologic function (cerebral performance categories 3 and 4) at hospital discharge and at 180 days, cognitive status and quality of life at 180 days, assessment of safety and harm. less thanbrgreater than less thanbrgreater thanDiscussion The TTM trial will investigate potential benefit and harm of 2 target temperature strategies, both avoiding hyperthermia in a large proportion of the out-of-hospital cardiac arrest population.
|
|
| 3. |
- Wyon, Nicholas
(author)
-
On the interaction between a neuromuscular blocking agent and regulation of breathing during hypoxia
- 2003
-
Doctoral thesis (other academic/artistic)abstract
- It was previously generally agreed that a mechanical train-of-four (TOF) ratio >0.70 represented an adequate recovery of respiratory function after neuromuscular blockade. Normal respiratory parameters at this level of recovery and during air breathing support this view. We doubted whether this level of recovery also was associated with a normal response to hypercarbic or hypoxic challenge. The aim of the first study was to investigate the influence of a partial neuromuscular block on the ventilatory responses to hypercarbia and hypoxemia. We found that a vecuronium-induced partial neuromuscular block, corresponding to a TOF-ratio of 0.70 is associated with a normal resting ventilation and ventilatory response to hypercarbia while a marked reduction in the ventilatory response to hypoxaemia was found. We conclude that a mechanical TOF ratio of 0.70 following vecuronium is associated with an inadequate ventilatory response to hypoxaemia. These findings, and the theory that they were caused by an interaction between vecuronium and the normal response to hypoxemia at the peripheral chemoreceptors of the carotid body, lead to our second study. Here we studied the effects of close carotid body injections of vecuronium on phrenic nerve activity, at different states of oxygenation, in anaesthetised and mechanically ventilated adult rabbits. A close carotid body injection of vecuronium reduced the hypoxia-induced increase in phrenic nerve activity. We conclude that this was most likely caused by a vecuronium-induced depression of carotid body chemosensitivity, but that further investigations were necessary to confirm this hypothesis. To elucidate whether this reduced response to hypoxic challenge was caused by an effect of Vecuronium on the peripheral chemo receptors, and not by a central effect, we designed a third study. This time we excluded central regulation by directly recording single fibre sinus nerve activity. The effect of systemic administration of vecuronium on a single fibre preparation of the carotid sinus nerve, was studied in seven mechanically ventilated rabbits. Our findings showed that systemic administration of vecuronium reversibly depresses the chemoreceptor function of the carotid body as measured on a single fibre afferent chemoreceptor preparation during hypoxia. We conclude that vecuronium, in addition to muscular paralysis, causes depression of carotid body chemoreceptor function during hypoxia and that the depression recovers spontaneously. To further demonstrate that the reduction in chemoreceptor activity observed in the previous experiments was being caused by an effect of the neuromuscular blocking agent on the peripheral receptor it was necessary to completely isolate the carotid body and sinus nerve from the rest of the organism. An isolated carotid body preparation with adjacent sinus nerve was used. Nicotine-induced carotid body responses were significantly depressed by the neuromuscular blocking agents vecuronium and atracurium. Increased dose caused an increased depression. We conclude that atracurium and vecuronium depress nicotine-induced chemoreceptor responses of the carotid body in a dose dependent manner and note that equipotent neuromuscular blocking concentrations give rise to a similar degree of chemoreceptor depression. Our findings have contributed to a change in attitude towards the clinical consequences of residual neuromuscular block. A TOF ratio of >=0.90 is now recommended for safe extubation, at which levels our research indicates that the hypoxic ventilatory response has recovered.
|
|
