Sugammadex in Ontario hospitals: Access and institutional policies.

RATIONALE AND AIMS: Sugammadex is a novel neuromuscular blockade reversal agent which rapidly reverses the effects of rocuronium and vecuronium. Compared with the first-generation neuromuscular blockade reversal agent, neostigmine, sugammadex has a number of superior properties; however, sugammadex is significantly more expensive per dose compared with neostigmine (~CAD$95 vs $4). Given the high cost of sugammadex, many Ontario hospitals either do not stock the drug or have specific policies on when the drug can be administered. This study was designed to determine access to sugammadex in Ontario hospitals, as well as the prevalence and content of institutional policies on its use. METHODS: We designed a survey assessing the availability of sugammadex and institutional policies on its use. We identified 60 Ontario hospitals with surgical services and obtained contact information for 45 of the anaesthesia departments. Surveys were sent to each department chief, and results were collected from July to October 2018. RESULTS: Thirty-four (75.6%) hospitals responded to the survey. Twenty-seven (79.4%) of the 34 respondent hospitals had sugammadex. Of the seven hospitals that did not have sugammadex, six were group B hospitals, and one was a paediatric hospital. Of the 27 hospitals with sugammadex, 16 (59.3%) hospitals had specific policies on when sugammadex may be used. Based on policies, sugammadex was most frequently allowed to be used in emergency situations, especially failed intubations or "can't intubate, can't ventilate" situations where 100% of policies allowed its use. Policies on specific patient populations for sugammadex use were uncommon, with 43.8% of existing hospital policies not specifying any patient populations. CONCLUSIONS: Though most hospitals have sugammadex available, there is a marked heterogeneity in hospital policies on its use. Given the high cost of sugammadex use, it is worthwhile to have evidence-based policies on its use. Judicious use of sugammadex may also have secondary cost-saving benefits, through improved operating room efficiency and decreased complication rates.

The paraventricular nucleus of the hypothalamus - a potential target for integrative treatment of autonomic dysfunction.

BACKGROUND: The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular). OBJECTIVES: Traditionally the PVN was viewed as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs, whether neuroendocrine or autonomic. Here we present data which suggest that the PVN plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition, we highlight recent work that suggests that dysfunction of such intranuclear integrative circuitry contributes to the pathology of conditions such as hypertension and congestive heart failure. CONCLUSIONS: This review highlights data showing that individual afferent inputs (subfornical organ), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.

Angiotensin depolarizes parvocellular neurons in paraventricular nucleus through modulation of putative nonselective cationic and potassium conductances.

Neurosecretory parvocellular neurons in the hypothalamic paraventricular nucleus (PVN) exercise considerable influence over the adenohypophysis and thus play a critical role in neuroendocrine regulation. ANG II has been demonstrated to act as a neurotransmitter in PVN, exerting significant impact on neuronal excitability and also influencing corticotrophin-releasing hormone secretion from the median eminence and, therefore, release of ACTH from the pituitary. We have used whole cell patch-clamp techniques in hypothalamic slices to examine the effects of ANG II on the excitability of neurosecretory parvocellular neurons. ANG II application resulted in a dose-dependent depolarization of neurosecretory neurons, a response that was maintained in tetrodotoxin (TTX), suggesting a direct mechanism of action. The depolarizing actions of this peptide were abolished by losartan, demonstrating these effects are AT(1) receptor mediated. Voltage-clamp analysis using slow voltage ramps revealed that ANG II activates a voltage-independent conductance with a reversal potential of -37.8 +/- 3.8 mV, suggesting ANG II effects on a nonselective cationic current. Further, a sustained potassium current characteristic of I(K) was significantly reduced (29.1 +/- 4.7%) by ANG II. These studies identify multiple postsynaptic modulatory sites through which ANG II can influence the excitability of neurosecretory parvocellular PVN neurons and, as a consequence of such actions, control hormonal secretion from the anterior pituitary.

Angiotensin II activates a nitric-oxide-driven inhibitory feedback in the rat paraventricular nucleus.

The hypothalamic paraventricular nucleus (PVN) has been shown to play major obligatory roles in autonomic and neuroendocrine regulation. Angiotensin II (ANG) acts as a neurotransmitter regulating the excitability of magnocellular neurons in this nucleus. We report here that ANG also activates a nitric-oxide-mediated negative feedback loop in the PVN that acts to regulate the functional output of magnocellular neurons. Thus in addition to its depolarizing actions on magnocellular neurons, ANG application results in an increase in the frequency of inhibitory postsynaptic potentials in a population of these neurons without effect on the amplitude of these events. ANG was also without significant effect on the mean frequency or amplitude of mini synaptic currents analyzed in voltage-clamp experiments. This increase in inhibitory input after ANG can be abolished by the nitric oxide synthase inhibitor Nomega-nitro-l-arginine methylester, demonstrating a requisite role for nitric oxide in the activation of this pathway. The depolarization of magnocellular neurons that show increased inhibitory postsynaptic potential (IPSP) frequency in response to ANG is significantly smaller than that observed in neurons in which IPSPs frequency was unaffected (3.2 +/- 1.1 vs. 8.0 +/- 0.5 mV, P < 0.05). Correspondingly, after nitric oxide synthase inhibition, the depolarizing effects of ANG on magnocellular neurons are augmented (2.0 +/- 0.7 vs. 6.7 +/- 0.7 mV, P < 0.05). The depolarization was also enhanced in the presence of the GABAergic antagonist bicuculline (1.9 +/- 1.2 vs. 11.9 +/- 2.3, P < 0.001). These data demonstrate that there exists within the PVN an intrinsic negative feedback loop that modulates neuronal excitability in response to peptidergic excitation.