Tracheal intubation in coronavirus disease 2019 (COVID-19) patients creates a risk to physiologically compromised patients and to attending healthcare providers. Clinical information on airway management and expert recommendations in these patients are urgently needed. By analysing a two-centre retrospective observational case series from Wuhan,

Central respiratory chemoreception is the mechanism by which the CNS maintains physiologically appropriate pH and PCO 2 via control of breathing. A prominent hypothesis holds that neural substrates for this process are distributed widely in the respiratory network, especially because many neurons that make up this network are chemosensitive in vitro. We and others have proposed that TASK channels (TASK-1, K 2P 3.1 and/or TASK-3, K 2P 9.1) may serve as molecular sensors for central chemoreception because they are highly expressed in multiple neuronal populations in the respiratory pathway and contribute to their pH sensitivity in vitro. To test this hypothesis, we examined the chemosensitivity of two prime candidate chemoreceptor neurons in vitro and tested ventilatory responses to CO 2 using TASK channel knock-out mice. The pH sensitivity of serotonergic raphe neurons was abolished in TASK channel knock-outs. In contrast, pH sensitivity of neurons in the mouse retrotrapezoid nucleus (RTN) was fully maintained in a TASK null background, and pharmacological evidence indicated that a K ϩ channel with properties distinct from TASK channels contributes to the pH sensitivity of rat RTN neurons. Furthermore, the ventilatory response to CO 2 was completely retained in single or double TASK knock-out mice. These data rule out a strict requirement for TASK channels or raphe neurons in central respiratory chemosensation. Furthermore, they indicate that a non-TASK K ϩ current contributes to chemosensitivity of RTN neurons, which are profoundly pH-sensitive and capable of driving respiratory output in response to local pH changes in vivo.

Output properties of neurons are greatly shaped by voltage-gated ion channels, whose biophysical properties and localization within axodendritic compartments serve to significantly transform the original input. The hyperpolarization-activated current, Ih, is mediated by HCN channels and plays a fundamental role in influencing neuronal excitability by regulating both membrane potential and input resistance. In neurons such as cortical and hippocampal pyramidal neurons, the subcellular localization of HCN channels plays critical functional role, yet mechanisms controlling HCN channel trafficking are not fully understood. Because ion channel function and localization are often influenced by interacting proteins, we generated a knockout mouse lacking the HCN channel auxiliary subunit, TRIP8b. Eliminating expression of TRIP8b dramatically reduced Ih expression in hippocampal pyramidal neurons. Loss of Ih-dependent membrane voltage properties was attributable to reduction of HCN channels on the neuronal surface, and there was a striking disruption of the normal expression pattern of HCN channels in pyramidal neuron dendrites. In heterologous cells and neurons, absence of TRIP8b increased HCN subunit targeting to and degradation by lysosomes. Mice lacking TRIP8b demonstrated motor learning deficits and enhanced resistance to multiple tasks of behavioral despair with high predictive validity for antidepressant efficacy. We observed similar resistance to behavioral despair in distinct mutant mice lacking HCN1 or HCN2. These data demonstrate that interaction with the auxiliary subunit TRIP8b is a major mechanism underlying proper expression of HCN channels and Ih in vivo, and suggest that targeting Ih may provide a novel approach to treatment of depression.

Ketamine has important anesthetic, analgesic, and psychotropic actions. It is widely believed that NMDA receptor inhibition accounts for ketamine actions, but there remains a dearth of behavioral evidence to support this hypothesis. Here, we present an alternative, behaviorally relevant molecular substrate for anesthetic effects of ketamine: the HCN1 pacemaker channels that underlie a neuronal hyperpolarization-activated cationic current (I h ). Ketamine caused subunit-specific inhibition of recombinant HCN1-containing channels and neuronal I h at clinically relevant concentrations; the channels were more potently inhibited by S-(ϩ)-ketamine than racemic ketamine, consistent with anesthetic actions of the compounds. In cortical pyramidal neurons from wild-type, but not HCN1 knock-out mice, ketamine induced membrane hyperpolarization and enhanced dendritosomatic synaptic coupling; both effects are known to promote cortical synchronization and support slow cortical rhythms, like those accompanying anesthetic-induced hypnosis. Accordingly, we found that the potency for ketamine to provoke a loss-of-righting reflex, a behavioral correlate of hypnosis, was strongly reduced in HCN1 knock-out mice. In addition, hypnotic sensitivity to two other intravenous anesthetics in HCN1 knock-out mice matched effects on HCN1 channels; propofol selectively inhibited HCN1 channels and propofol sensitivity was diminished in HCN1 knock-out mice, whereas etomidate had no effect on HCN1 channels and hypnotic sensitivity to etomidate was unaffected by HCN1 gene deletion. These data advance HCN1 channels as a novel molecular target for ketamine, provide a plausible neuronal mechanism for enhanced cortical synchronization during anesthetic-induced hypnosis and suggest that HCN1 channels might contribute to other unexplained actions of ketamine.

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When inappropriate for salt status, the mineralocorticoid aldosterone induces cardiac and renal injury. Autonomous overproduction of aldosterone from the adrenal zona glomerulosa (ZG) is also the most frequent cause of secondary hypertension. Yet, the etiology of nontumorigenic primary hyperaldosteronism caused by bilateral idiopathic hyperaldosteronism remains unknown. Here, we show that genetic deletion of TWIK-related acid-sensitive K (TASK)-1 and TASK-3 channels removes an important background K current that results in a marked depolarization of ZG cell membrane potential. Although TASK channel deletion mice (TASK −/− ) adjust urinary Na excretion and aldosterone production to match Na intake, they produce more aldosterone than control mice across the range of Na intake. Overproduction of aldosterone is not the result of enhanced activity of the renin–angiotensin system because circulating renin concentrations remain either unchanged or lower than those of control mice at each level of Na intake. In addition, TASK −/− mice fail to suppress aldosterone production in response to dietary Na loading. Autonomous aldosterone production is also demonstrated by the failure of an angiotensin type 1 receptor blocker, candesartan, to normalize aldosterone production to control levels in TASK −/− mice. Thus, TASK −/− channel knockout mice exhibit the hallmarks of primary hyperaldosteronism. Our studies establish an animal model of nontumorigenic primary hyperaldosteronism and identify TASK channels as a possible therapeutic target for primary hyperaldosteronism.

Interventions: Anesthetic management and infection control guidelines for emergency procedures for patients with suspected 2019-nCoV were drafted and applied in 4 hospitals in Wuhan. Measurements and Main Results: Cross-infection in the operating rooms of the 4 hospitals was effectively reduced by implementing the new measures and procedures. The majority of patients with laboratory-confirmed 2019-nCoV infection or suspected infection were female (23 [62%] of 37), and the mean age was 41.0 years old (standard deviation 19.6; range 4-78). 10 (27%) patients had chronic medical illnesses, including 4 (11%) with diabetes, 8 (22%) with hypertension, and 8 (22%) with digestive system disease. Twenty-five (68%) patients presented with lymphopenia, and 23 (62%) patients exhibited multiple mottling and ground-glass opacity on computed tomography scanning. Conclusions: The present study indicates that COVID 19Àspecific guidelines for emergency procedures for patients with confirmed or suspected 2019-nCoV may effectively prevent cross-infection in the operating room. Most patients with confirmed or suspected COVID 19 presented with fever and dry cough and demonstrated bilateral multiple mottling and ground-glass opacity on chest computed tomography scans. Ó 2020 Elsevier Inc. All rights reserved.

The outbreak of the new Coronavirus disease, COVID-19, has been involved in 77,262 cases in China as well as in 27 other countries as of February 24, 2020. Because the virus is novel to human beings, and there is no vaccine yet available, every individual is susceptible and can become infected. Healthcare workers are at high risk, and unfortunately, more than 3,000 healthcare workers in China have been infected. Anesthesiologists are among healthcare workers who are at an even higher risk of becoming infected because of their close contact with infected patients and high potential of exposure to respiratory droplets or aerosol from their patients’ airways. In order to provide healthcare workers with updated recommendations on the management of patients in the perioperative setting as well as for emergency airway management outside of the operating room, the two largest anesthesia societies, the Chinese Society of Anesthesiology (CSA) and the Chinese Association of Anesthesiologists (CAA) have formed a task force to produce the recommendations. The task force hopes to help healthcare workers, particularly anesthesiologists, optimize the care of their patients and protect patients, healthcare workers, and the public from becoming infected. The recommendations were created mainly based on the practice and experience of anesthesiologists who provide care to patients in China. Therefore, adoption of these recommendations outside of China must be done with caution, and the local environment, culture, uniqueness of the healthcare system, and patients’ needs should be considered. The task force will continuously update the recommendations and incorporate new information in future versions.