Experimental validation of a portable tidal volume indicator for bag valve mask ventilation.

INTRODUCTION: Short-term emergency ventilation is most typically accomplished through bag valve mask (BVM) techniques. BVMs like the AMBU® bag are cost-effective and highly portable but are also highly prone to user error, especially in high-stress emergent situations. Inaccurate and inappropriate ventilation has the potential to inflict great injury to patients through hyper- and hypoventilation. Here, we present the BVM Emergency Narration-Guided Instrument (BENGI) - a tidal volume feedback monitoring device that provides instantaneous visual and audio feedback on delivered tidal volumes, respiratory rates, and inspiratory/expiratory times. Providing feedback on the depth and regularity of respirations enables providers to deliver more consistent and accurate tidal volumes and rates. We describe the design, assembly, and validation of the BENGI as a practical tool to reduce manual ventilation-induced lung injury. METHODS: The prototype BENGI was assembled with custom 3D-printed housing and commercially available electronic components. A mass flow sensor in the central channel of the device measures air flow, which is used to calculate tidal volume. Tidal volumes are displayed via an LED ring affixed to the top of the BENGI. Additional feedback is provided through a speaker in the device. Central processing is accomplished through an Arduino microcontroller. Validation of the BENGI was accomplished using benchtop simulation with a clinical ventilator, BVM, and manikin test lung. Known respiratory quantities were delivered by the ventilator which were then compared to measurements from the BENGI to validate the accuracy of flow measurements, tidal volume calculations, and audio cue triggers. RESULTS: BENGI tidal volume measurements were found to lie within 4% of true delivered tidal volume values (95% CI of 0.53 to 3.7%) when breaths were delivered with 1-s inspiratory times, with similar performance for breaths delivered with 0.5-s inspiratory times (95% CI of 1.1 to 6.7%) and 2-s inspiratory times (95% CI of -1.1 to 2.3%). Audio cues "Bag faster" (1.84 to 2.03 s), "Bag slower" (0.35 to 0.41 s), and "Leak detected" (43 to 50%) were triggered close to target trigger values (2.00 s, 0.50 s, and 50%, respectively) across varying tidal volumes. CONCLUSIONS: The BENGI achieved its proposed goals of accurately measuring and reporting tidal volumes delivered through BVM systems, providing immediate feedback on the quality of respiratory performance through audio and visual cues. The BENGI has the potential to reduce manual ventilation-induced lung injury and improve patient outcomes by providing accurate feedback on ventilatory parameters.

Efficacy and safety testing of a COVID-19 era emergency ventilator in a healthy rabbit lung model.

BACKGROUND: The COVID-19 pandemic revealed a substantial and unmet need for low-cost, easily accessible mechanical ventilation strategies for use in medical resource-challenged areas. Internationally, several groups developed non-conventional COVID-19 era emergency ventilator strategies as a stopgap measure when conventional ventilators were unavailable. Here, we compared our FALCON emergency ventilator in a rabbit model and compared its safety and functionality to conventional mechanical ventilation. METHODS: New Zealand white rabbits (n = 5) received mechanical ventilation from both the FALCON and a conventional mechanical ventilator (Engström Carestation™) for 1 h each. Airflow and pressure, blood O2 saturation, end tidal CO2, and arterial blood gas measurements were measured. Additionally, gross and histological lung samples were compared to spontaneously breathing rabbits (n = 3) to assess signs of ventilator induced lung injury. RESULTS: All rabbits were successfully ventilated with the FALCON. At identical ventilator settings, tidal volumes, pressures, and respiratory rates were similar between both ventilators, but the inspiratory to expiratory ratio was lower using the FALCON. End tidal CO2 was significantly higher on the FALCON, and arterial blood gas measurements demonstrated lower arterial partial pressure of O2 at 30 min and higher arterial partial pressure of CO2 at 30 and 60 min using the FALCON. However, when ventilated at higher respiratory rates, we observed a stepwise decrease in end tidal CO2. Poincaré plot analysis demonstrated small but significant increases in short-term and long-term variation of peak inspiratory pressure generation from the FALCON. Wet to dry lung weight and lung injury scoring between the mechanically ventilated and spontaneously breathing rabbits were similar. CONCLUSIONS: Although conventional ventilators are always preferable outside of emergency use, the FALCON ventilator safely and effectively ventilated healthy rabbits without lung injury. Emergency ventilation using accessible and inexpensive strategies like the FALCON may be useful for communities with low access to medical resources and as a backup form of emergency ventilation.

Occipital Nerve Stimulation: An Alternative Treatment of Chronic Migraine.

PURPOSE OF REVIEW: This paper will examine the efficacy and safety of occipital nerve stimulation as a non-pharmacological alternative treatment for migraine. RECENT FINDINGS: Migraine is characterized as a primary headache disorder with possible premonitory and aura phases, both of which vary greatly in symptomatology. The most common treatments for chronic migraine are pharmacological and are aimed at both acute relief (e.g., nonsteroidal anti-inflammatory drugs, triptans, and ergots) and prophylaxis (e.g., propranolol, valproic acid, and topiramate). For patients with medically refractory migraine, acute relief medication overuse can increase the risk of developing more severe and more frequent migraine attacks. Occipital nerve stimulation is a non-pharmacological alternative treatment for chronic migraine, which could eliminate the risk of adverse effects from acute relief medication overuse. Neurostimulation is thought to prevent pain by blocking signal transduction from small nociceptive fibers with non-painful signaling in larger adjacent fibers. Existing data from clinical trials support the overall safety and efficacy of occipital nerve stimulation for the treatment of chronic migraine. However, few large controlled, double-blinded studies have been conducted, due to both practical and ethical concerns. Currently, occipital nerve stimulation is available as an off-label use of neurostimulation for pain prevention but is not approved by the FDA specifically for the treatment of chronic migraine.

The Antisense Oligonucleotide Nusinersen for Treatment of Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a rare, autosomal recessive neuromuscular degenerative disease characterized by loss of spinal cord motor neurons leading to progressive muscle wasting. The most common pathology results from a homozygous disruption in the survival motor neuron 1 (SMN1) gene on chromosome 5q13 via deletion, conversion, or mutation. SMN2 is a near duplicate of SMN1 that can produce full-length SMN mRNA transcripts, but its overall production capability of these mRNA transcripts is lower than that seen in SMN1. This leads to lower levels of functional SMN protein within motor neurons. The FDA approved nusinersen in December 2016 to treat SMA associated with SMN1 gene mutation. It is administered directly to the central nervous system by intrathecal injection. An antisense oligonucleotide (ASO) drug, nusinersen, provides an upcoming and promising treatment option for SMA and represents a novel pharmacological approach with a mechanism of action relevant for other neurodegenerative disorders. Nusinersen begins with four initial loading doses that are followed by three maintenance doses per year. Three major studies (CHERISH, ENDEAR, and NURTURE) have shown to improve motor function in early and late-onset individuals and reduce the chances of ventilator requirements in pre-symptomatic infants. Studies investigating the timing of drug delivery in mouse models of SMA report the best outcomes when drugs are delivered early before any significant motor function is lost. Nusinersen is a novel therapeutic approach with consistent results in all three studies and is proof of the novel concept for treating SMA and other neurodegenerative disorders in the future.

Brexpiprazole for the Treatment of Schizophrenia and Major Depressive Disorder: A Comprehensive Review of Pharmacological Considerations in Clinical Practice.

Mood and psychotic disorders are a group of illnesses that affect behavior and cognition. Schizophrenia is characterized by positive symptoms, such as delusions and hallucinations, as well as negative symptoms. Major depressive disorder (MDD) is a mood disorder that affects the patient's emotions, energy, and motivation. Brexpiprazole works as a partial agonist at serotonin 5-hydroxytryptamine1A and dopamine D2 receptors and an antagonist at serotonin 5-hydroxytryptamine2A. Schizophrenia and MDD have a wide range of risk factors, both biological and environmental. Third generation antipsychotics, which include brexpiprazole, are the latest group of drugs to reach the market, demonstrating efficacy and tolerability. Patients with acute schizophrenia have responded well to brexpiprazole. In this regard, in patients who have MDD plus anxiety symptoms, brexpiprazole can be effective as an adjunctive therapy and can reduce anxiety symptoms. In summary, brexpiprazole has proved to be an effective alternative to typical or first and second-generation atypical antipsychotics.