Blackburn MB, Andrade MA, Toney GM. Hypothalamic PVN contributes to acute intermittent hypoxia-induced sympathetic but not phrenic long-term facilitation. J Appl Physiol 124: 1233-1243, 2018. First published December 19, 2017; doi: 10.1152/japplphysiol.00743.2017 .- Acute intermittent hypoxia (AIH) repetitively activates the arterial chemoreflex and triggers a progressive increase of sympathetic nerve activity (SNA) and phrenic nerve activity (PNA) referred to as sympathetic and phrenic long-term facilitation (S-LTF and P-LTF), respectively. Neurons of the hypothalamic paraventricular nucleus (PVN) participate in the arterial chemoreflex, but their contribution to AIH-induced LTF is unknown. To determine this, anesthetized rats were vagotomized and exposed to 10 cycles of AIH, each consisting of ventilation for 3 min with 100% O followed by 3 min with 15% O. Before AIH, rats received bilateral PVN injections of artificial cerebrospinal fluid (aCSF; vehicle) or the GABA-A receptor agonist muscimol (100 pmol in 50 nl) to inhibit neuronal activity. Thirty minutes after completing the AIH protocol, during which rats were continuously ventilated with 100% O, S-LTF and P-LTF were quantified from recordings of integrated splanchnic SNA and PNA, respectively. PVN muscimol attenuated increases of SNA during hypoxic episodes occurring in later cycles (6-10) of AIH ( P < 0.03) and attenuated post-AIH S-LTF ( P < 0.001). Muscimol, however, did not consistently affect peak PNA responses during hypoxic episodes and did not alter AIH-induced P-LTF. These findings indicate that PVN neuronal activity contributes to sympathetic responses during AIH and to subsequent generation of S-LTF. NEW & NOTEWORTHY Neural circuits mediating acute intermittent hypoxia (AIH)-induced sympathetic and phrenic long-term facilitation (LTF) have not been fully elucidated. We found that paraventricular nucleus (PVN) inhibition attenuated sympathetic activation during episodes of AIH and reduced post-AIH sympathetic LTF. Neither phrenic burst patterning nor the magnitude of AIH-induced phrenic LTF was affected. Findings indicate that PVN neurons contribute to AIH-induced sympathetic LTF. Defining mechanisms of sympathetic LTF could improve strategies to reduce sympathetic activity in cardiovascular and metabolic diseases.

ANG II-salt hypertension selectively increases splanchnic sympathetic nerve activity (sSNA), but the extent to which this reflects increased respiratory versus cardiac rhythmic bursting is unknown. Here, integrated sSNA was elevated in ANG II-infused rats fed a high-salt (2% NaCl) diet (ANG II-HSD) compared with vehicle-infused rats fed a normal-salt (0.4% NaCl) diet (Veh-NSD; P < 0.01). Increased sSNA was not accompanied by increased inspiratory or expiratory bursting, consistent with no group difference in central inspiratory drive. Consistent with preserved inhibitory baroreflex entrainment of elevated sSNA in ANG II-HSD rats, the time integral ( P < 0.05) and amplitude ( P < 0.01) of cardiac rhythmic sSNA were increased. Consistent with activity of hypothalamic paraventricular nucleus (PVN) neurons supporting basal SNA in ANG II-salt hypertension, inhibition of PVN with the GABA-A receptor agonist muscimol reduced mean arterial pressure (MAP) and integrated sSNA only in the ANG II-HSD group ( P < 0.001). PVN inhibition had no effect on respiratory rhythmic sSNA bursting in either group but reduced cardiac rhythmic sSNA in ANG II-HSD rats only ( P < 0.01). The latter likely reflected reduced inhibitory baroreflex entrainment subsequent to the fall of MAP. Of note is that MAP as well as integrated and rhythmic burst patterns of sSNA were similar in vehicle-infused rats whether they were fed a normal or high-salt diet. Findings indicate that PVN neurons support elevated sSNA in ANG II-HSD rats by driving a tonic component of activity without altering respiratory or cardiac rhythmic bursting. Because sSNA was unchanged in Veh-HSD rats, activation of PVN-driven tonic sSNA appears to require central actions of ANG II. NEW & NOTEWORTHY ANG II-salt hypertension is strongly neurogenic and depends on hypothalamic paraventricular nucleus (PVN)-driven splanchnic sympathetic nerve activity (sSNA). Here, respiratory and cardiac bursts of sSNA were preserved in ANG II-salt rats and unaltered by PVN inhibition, suggesting that PVN neurons drive a tonic component of sSNA rather than modulating dominant patterns of burst discharge.

Summary Airway simulators, or training manikins, are frequently used in research studies for device development and training purposes. This study was designed to determine the anatomic accuracy of the most frequently used low‐fidelity airway training manikins. Computerised tomography scans and ruler measurements were taken of the SynDaver®, Laerdal® and AirSim® manikins. These measurements were compared with human computerised tomography (CT) scans (n = 33) from patients at the University of Michigan Medical Center or previously published values. Manikin measurements were scored as a percentile among the distribution of the same measurements in the human population and 10 out of 27 manikin measurements (nine measurements each in three manikins) were outside of two standard deviations from the mean in the participants. All three manikins were visually identifiable as outliers when plotting the first two dimensions from multidimensional scaling. In particular, the airway space between the epiglottis and posterior pharyngeal wall, through which airway devices must pass, was too large in all three manikins. SynDaver, Laerdal and AirSim manikins do not have anatomically correct static dimensions in relation to humans and these inaccuracies may lead to imprecise airway device development, negatively affect training and cause over‐confidence in users.

Introduction Airway compromise is the second leading cause of potentially survivable death on the battlefield. The purpose of this study was to better understand wartime prehospital airway patients. Materials and Methods The Role 2 Database (R2D) was retrospectively reviewed for adult patients injured in Afghanistan between February 2008 and September 2014. Of primary interest were prehospital airway interventions and mortality. Prehospital combat mortality index (CMI-PH), hemodynamic interventions, injury mechanism, and demographic data were also included in various statistical analyses. Results A total of 12,780 trauma patients were recorded in the R2D of whom 890 (7.0%) received prehospital airway intervention. Airway intervention was more common in patients who ultimately died (25.3% vs. 5.6%); however, no statistical association was found in a multivariable logistic regression model (OR 1.28, 95% CI 0.98–1.68). Compared with U.S. military personnel, other military patients were more likely to receive airway intervention after adjusting for CMI-PH (OR 1.33, 95% CI 1.07–1.64). Conclusions In the R2D, airway intervention was associated with increased odds of mortality, although this was not statistically significant. Other patients had higher odds of undergoing an airway intervention than U.S. military. Awareness of these findings will facilitate training and equipment for future management of prehospital/prolonged field care airway interventions.

Prognostic and epidemiological study, level III.

WARNING RISK OF CARDIAC ARREST FROM HYPERKALEMIC RHABDOMYOLYSIS There have been rare reports of acute rhabdomyolysis with hyperkalemia followed by ventricular dysrhythmias, cardiac arrest, and death after the administration of succinylcholine to apparently healthy children who were subsequently found to have undiagnosed skeletal muscle myopathy, most frequently Duchenne's muscular dystrophy. This syndrome often presents as peaked T-waves and sudden cardiac arrest within minutes after the administration of the drug in healthy appearing children (usually, but not exclusively, males, and most frequently 8 years of age or younger). There have also been reports in adolescents. Therefore, when a healthy appearing infant or child develops cardiac arrest soon after administration of succinylcholine not felt to be due to inadequate ventilation, oxygenation, or anesthetic overdose, immediate treatment for hyperkalemia should be instituted. This should include administration of intravenous calcium, bicarbonate, and glucose with insulin, with hyperventilation. Due to the abrupt onset of this syndrome, routine resuscitative measures are likely to be unsuccessful. However, extraordinary and prolonged resuscitative efforts have resulted in successful resuscitation in some reported cases. In addition, in the presence of signs of malignant hyperthermia, appropriate treatment should be instituted concurrently. Since there may be no signs or symptoms to alert the practitioner to which patients are at risk, it is recommended that the use of succinylcholine in children should be reserved for emergency intubation or instances where immediate securing of the airway is necessary, e.g. laryngospasm, difficult airway, full stomach, or for intramuscular use when a suitable vein is inaccessible (see PRECAUTIONS: Pediatric Use and DOSAGE AND ADMINISTRATION). This drug should be used only by individuals familiar with its actions, characteristics, and hazards. DESCRIPTION ANECTINE (succinylcholine chloride) is an ultra short-acting depolarizing-type, skeletal muscle relaxant for intravenous (IV) administration.

Proper placement of the tracheal tube requires confirmation, and the predominant method in addition to clinical signs is the presence of end-tidal carbon dioxide. Such is the importance of confirmation that novel methods may also have a place. We previously demonstrated using ex-vivo swine tissue a unique spectral reflectance characteristic of tracheal tissue that differs from oesophageal tissue. We hypothesised that this characteristic would be present in living swine tissue and human cadavers. Reflectance spectra in the range 500-650 nm were captured using a customised fibreoptic probe, compact spectrometer and white light source from both the trachea and the oesophagus in anesthetised living swine and in human cadavers. A tracheal detection algorithm using ratio comparisons of reflectance was developed. The existence of the unique tracheal characteristic in both in-vivo swine and cadaver models was confirmed (p < 0.0001 for all comparisons between tracheal and oesophageal tissue at all target wavelengths in both species). Furthermore, our proposed tracheal detection algorithm exhibited a 100% positive predictive value in both models. This has potential utility for incorporation into airway management devices.

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