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OBJECTIVES: Experimental models suggest that prone position and positive end-expiratory pressure (PEEP) homogenize ventral-dorsal ventilation distribution and regional respiratory compliance. However, this response still needs confirmation on humans. Therefore, this study aimed to assess the changes in global and regional respiratory mechanics in supine and prone positions over a range of PEEP levels in acute respiratory distress syndrome (ARDS) patients. DESIGN: A prospective cohort study. PATIENTS: Twenty-two intubated patients with ARDS caused by COVID-19 pneumonia. INTERVENTIONS: Electrical impedance tomography and esophageal manometry were applied during PEEP titrations from 20 cm H2O to 6 cm H2O in supine and prone positions. MEASUREMENTS: Global respiratory system compliance (Crs), chest wall compliance, regional lung compliance, ventilation distribution in supine and prone positions. MAIN RESULTS: Compared with supine position, the maximum level of Crs changed after prone position in 59% of ARDS patients (n = 13), of which the Crs decreased in 32% (n = 7) and increased in 27% (n = 6). To reach maximum Crs after pronation, PEEP was changed in 45% of the patients by at least 4 cm H2O. After pronation, the ventilation and compliance of the dorsal region did not consistently change in the entire sample of patients, increasing specifically in a subgroup of patients who showed a positive change in Crs when transitioning from supine to prone position. These combined changes in ventilation and compliance suggest dorsal recruitment postpronation. In addition, the subgroup with increased Crs postpronation demonstrated the most pronounced difference between dorsal and ventral ventilation distribution from supine to prone position (p = 0.01), indicating heterogeneous ventilation distribution in prone position. CONCLUSIONS: Prone position modifies global respiratory compliance in most patients with ARDS. Only a subgroup of patients with a positive change in Crs postpronation presented a consistent improvement in dorsal ventilation and compliance. These data suggest that the response to pronation on global and regional mechanics can vary among ARDS patients, with some patients presenting more dorsal lung recruitment than others.
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Rationale: The effects of high-dose inhaled nitric oxide on hypoxemia in coronavirus disease (COVID-19) acute respiratory failure are unknown. Objectives: The primary outcome was the change in arterial oxygenation (PaO2/FiO2) at 48 hours. The secondary outcomes included: time to reach a PaO2/FiO2.300mmHg for at least 24 hours, the proportion of participants with a PaO2/FiO2.300mmHg at 28 days, and survival at 28 and at 90 days. Methods: Mechanically ventilated adults with COVID-19 pneumonia were enrolled in a phase II, multicenter, single-blind, randomized controlled parallel-arm trial. Participants in the intervention arm received inhaled nitric oxide at 80 ppm for 48 hours, compared with the control group receiving usual care (without placebo). Measurements and Main Results: A total of 193 participants were included in the modified intention-to-treat analysis. The mean change in PaO2/FiO2 ratio at 48 hours was 28.3mmHg in the intervention group and 21.4mmHg in the control group (mean difference, 39.1mmHg; 95% credible interval [CrI], 18.1 to 60.3). The mean time to reach a PaO2/FiO2.300mmHg in the interventional group was 8.7 days, compared with 8.4 days for the control group (mean difference, 0.44; 95% CrI, 23.63 to 4.53). At 28 days, the proportion of participants attaining a PaO2/FiO2.300mmHg was 27.7% in the inhaled nitric oxide group and 17.2% in the control subjects (risk ratio, 2.03; 95% CrI, 1.11 to 3.86). Duration of ventilation and mortality at 28 and 90 days did not differ. No serious adverse events were reported. Conclusions: The use of high-dose inhaled nitric oxide resulted in an improvement of PaO2/FiO2 at 48 hours compared with usual care in adults with acute hypoxemic respiratory failure due to COVID-19.
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COVID-19 , Insuficiencia Respiratoria , Adulto , Humanos , Óxido Nítrico/uso terapéutico , COVID-19/complicaciones , Método Simple Ciego , Insuficiencia Respiratoria/tratamiento farmacológico , Insuficiencia Respiratoria/etiología , Respiración Artificial , Administración por InhalaciónRESUMEN
We report a 10-year-old boy with a de novo pathogenic variant in ALDH18A1, a rare form of metabolic cutis laxa, which was complicated by atlantoaxial instability and spinal cord compression following a fall from standing height. The patient required emergent cervical spine fusion and decompression followed by a 2-month hospitalization and rehabilitation. In addition to the core clinical features of joint and skin laxity, hypotonia, and developmental delays, we expand the connective tissue phenotype by adding a new potential feature of cervical spine instability. Patients with pathogenic variants in ALDH18A1 may warrant cervical spine screening to minimize possible morbidity. Neurosurgeons, geneticists, primary care providers, and families should be aware of the increased risk of severe cervical injury from minor trauma.
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Cutis Laxo , Inestabilidad de la Articulación , Enfermedades de la Columna Vertebral , Masculino , Humanos , Niño , Inestabilidad de la Articulación/diagnóstico , Inestabilidad de la Articulación/genética , Cutis Laxo/genética , Mutación , Vértebras Cervicales/cirugía , Vértebras Cervicales/patologíaRESUMEN
BACKGROUND: Several nitric oxide (NO) generating devices have been developed to deliver NO between 1 part per million (ppm) and 80 ppm. Although inhalation of high-dose NO may exert antimicrobial effects, the feasibility and safety of producing high-dose (more than 100 ppm) NO remains to be established. In the current study, we designed, developed, and tested three high-dose NO generating devices. METHODS: We constructed three NO generating devices: a double spark plug NO generator, a high-pressure single spark plug NO generator, and a gliding arc NO generator. The NO and NO2 concentrations were measured at different gas flows and under various atmospheric pressures. The double spark plug NO generator was designed to deliver gas through an oxygenator and mixing with pure oxygen. The high-pressure and gliding arc NO generators were used to deliver gas through a ventilator into artificial lungs to mimic delivering high-dose NO in the clinical settings. The energy consumption was measured and compared among the three NO generators. RESULTS: The double spark plug NO generator produced 200 ± 2 ppm (mean ± SD) of NO at gas flow of 8 L/min (or 320 ± 3 ppm at gas flow of 5 L/min) with electrode gap of 3 mm. The nitrogen dioxide (NO2) levels were below 3.0 ± 0.1 ppm when mixing with various volumes of pure oxygen. The addition of a second generator increased the delivered NO from 80 (with one spark plug) to 200 ppm. With the high-pressure chamber, the NO concentration reached 407 ± 3 ppm with continuous air flow at 5 L/min when employing the 3 mm electrode gap under 2.0 atmospheric pressure (ATA). When compared to 1 ATA, NO production was increased 22% at 1.5 ATA and 34% at 2 ATA. The NO level was 180 ± 1 ppm when connecting the device to a ventilator with a constant inspiratory airflow of 15 L/min, and NO2 levels were below 1 (0.93 ± 0.02) ppm. The gliding arc NO generator produced up to 180 ± 4 ppm of NO when connecting the device to a ventilator, and the NO2 level was below 1 (0.91 ± 0.02) ppm in all testing conditions. The gliding arc device required more power (in watts) to generate the same concentrations of NO when compared to double spark plug or high-pressure NO generators. CONCLUSIONS: Our results demonstrated that it is feasible to enhance NO production (more than 100 ppm) while maintaining NO2 level relatively low (less than 3 ppm) with the three recently developed NO generating devices. Future studies might include these novel designs to deliver high doses of inhaled NO as an antimicrobial used to treat upper and lower respiratory tract infections.
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Óxido Nítrico , Dióxido de Nitrógeno , Terapia Respiratoria , Pulmón , Administración por Inhalación , OxígenoRESUMEN
OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) has been used successfully to support adults with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related cardiac or respiratory failure refractory to conventional therapies. Comprehensive reports of children and adolescents with SARS-CoV-2-related ECMO support for conditions, including multisystem inflammatory syndrome in children (MIS-C) and acute COVID-19, are needed. DESIGN: Case series of patients from the Overcoming COVID-19 public health surveillance registry. SETTING: Sixty-three hospitals in 32 U.S. states reporting to the registry between March 15, 2020, and December 31, 2021. PATIENTS: Patients less than 21 years admitted to the ICU meeting Centers for Disease Control criteria for MIS-C or acute COVID-19. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The final cohort included 2,733 patients with MIS-C ( n = 1,530; 37 [2.4%] requiring ECMO) or acute COVID-19 ( n = 1,203; 71 [5.9%] requiring ECMO). ECMO patients in both groups were older than those without ECMO support (MIS-C median 15.4 vs 9.9 yr; acute COVID-19 median 15.3 vs 13.6 yr). The body mass index percentile was similar in the MIS-C ECMO versus no ECMO groups (89.9 vs 85.8; p = 0.22) but higher in the COVID-19 ECMO versus no ECMO groups (98.3 vs 96.5; p = 0.03). Patients on ECMO with MIS-C versus COVID-19 were supported more often with venoarterial ECMO (92% vs 41%) for primary cardiac indications (87% vs 23%), had ECMO initiated earlier (median 1 vs 5 d from hospitalization), shorter ECMO courses (median 3.9 vs 14 d), shorter hospital length of stay (median 20 vs 52 d), lower in-hospital mortality (27% vs 37%), and less major morbidity at discharge in survivors (new tracheostomy, oxygen or mechanical ventilation need or neurologic deficit; 0% vs 11%, 0% vs 20%, and 8% vs 15%, respectively). Most patients with MIS-C requiring ECMO support (87%) were admitted during the pre-Delta (variant B.1.617.2) period, while most patients with acute COVID-19 requiring ECMO support (70%) were admitted during the Delta variant period. CONCLUSIONS: ECMO support for SARS-CoV-2-related critical illness was uncommon, but type, initiation, and duration of ECMO use in MIS-C and acute COVID-19 were markedly different. Like pre-pandemic pediatric ECMO cohorts, most patients survived to hospital discharge.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Adulto , Humanos , Niño , Adolescente , COVID-19/terapia , SARS-CoV-2 , Hospitalización , Unidades de Cuidados Intensivos , Estudios RetrospectivosRESUMEN
Access to medical technologies is a critical component of universal access to care; however, the advancement of technologies for children has historically lagged behind those for adults. The small market size, anatomic and physiologic variability, and legal and ethical implications pose unique barriers to developing and commercialising paediatric biomedical innovations. These challenges are magnified in low-resource settings (LRS), which often lack appropriate regulatory oversight, support for service contracts, and supply chain capacity. The COVID-19 pandemic exposed shortcomings in the traditional industry model for medical technologies, while also catalysing open-source approaches to technology development and dissemination. Open-source pathways - where products are freely licenced to be distributed and modified - addressed key shortages in critical equipment. Relatedly, we argue that open-source approaches can accelerate paediatric global health technology development. Open-source approaches can be tailored to clinical challenges independent of economic factors, embrace low-cost manufacturing techniques, and can be highly customisable. Furthermore, diverse stakeholders, including families and patients, are empowered to participate in collaborative communities of practice. How to regulate the development, manufacture, and distribution of open-source technologies remains an ongoing area of exploration. The need for democratised innovation must be carefully balanced against the imperatives of safety and quality for paediatric-specific solutions. This can be achieved, in part, through close coordination between national regulatory agencies and decentralised networks where products can be peer-reviewed and tested. Altogether, there is significant potential for open source to advance more equitable and sustainable medical innovations for all children.
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Tecnología Biomédica , COVID-19 , Salud Global , Humanos , COVID-19/epidemiología , Niño , Pediatría , SARS-CoV-2 , PandemiasRESUMEN
OBJECTIVE: To evaluate whether the use of inhaled nitric oxide (iNO)200 improves respiratory function. METHODS: This retrospective cohort study used data from pregnant patients hospitalized with severe bilateral coronavirus disease 2019 (COVID-19) pneumonia at four teaching hospitals between March 2020 and December 2021. Two cohorts were identified: 1) those receiving standard of care alone (SoC cohort) and 2) those receiving iNO200 for 30 minutes twice daily in addition to standard of care alone (iNO200 cohort). Inhaled nitric oxide, as a novel therapy, was offered only at one hospital. The prespecified primary outcome was days free from any oxygen supplementation at 28 days postadmission. Secondary outcomes were hospital length of stay, rate of intubation, and intensive care unit (ICU) length of stay. The multivariable-adjusted regression analyses accounted for age, body mass index, gestational age, use of steroids, remdesivir, and the study center. RESULTS: Seventy-one pregnant patients were hospitalized for severe bilateral COVID-19 pneumonia: 51 in the SoC cohort and 20 in the iNO200 cohort. Patients receiving iNO200 had more oxygen supplementation-free days (iNO200: median [interquartile range], 24 [23-26] days vs standard of care alone: 22 [14-24] days, P=.01) compared with patients in the SoC cohort. In the multivariable-adjusted analyses, iNO200 was associated with 63.2% (95% CI 36.2-95.4%; P<.001) more days free from oxygen supplementation, 59.7% (95% CI 56.0-63.2%; P<.001) shorter ICU length of stay, and 63.6% (95% CI 55.1-70.8%; P<.001) shorter hospital length of stay. No iNO200-related adverse events were reported. CONCLUSION: In pregnant patients with severe bilateral COVID-19 pneumonia, iNO200 was associated with a reduced need for oxygen supplementation and shorter hospital stay.
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Tratamiento Farmacológico de COVID-19 , Femenino , Humanos , Óxido Nítrico , Oxígeno , Embarazo , Estudios Retrospectivos , SARS-CoV-2RESUMEN
BACKGROUND: Distribution of long-lasting insecticide treated nets (LLINs) is the most widely used intervention for the prevention of malaria but recall and social desirability biases may lead to challenges in accurately measuring use of bednets. SmartNet is a remote electronic monitor that provides objective measurements of bednet use over weeks at a time. Assessing local acceptability is important when implementing innovative global health technologies such as SmartNet. This study draws on established models such as the Technology Acceptance Model (TAM) and Theoretical Framework of Acceptability (TFA) to assess acceptability of SmartNet in Ugandan households. METHODS: Semi-structured qualitative interviews were conducted at weeks one and six following installation of SmartNet in ten households in Western Uganda. Heads-of-households answered open-ended questions addressing the main acceptability domains of the TFA and TAM models (i.e. perceived ease of use, ethicality, etc.). Responses were digitally recorded, transcribed, coded and analyzed using a thematic analysis approach. RESULTS: Seven out of ten households interviewed reported no difference in use between SmartNet and a standard LLIN. Households stated the large size, soft fabric, and the efficacy of SmartNet relative to a standard LLIN contributed to perceived usefulness and perceived ease of use. Opportunity costs of the novel monitoring system expressed by households included difficulty washing nets and dislike of blinking lights on the device. Barriers to SmartNet use focused on questions of the ethics of bednet use monitoring, discomfort with technical aspects of the device and a poor understanding of its function amongst others in the community. However, explaining SmartNet to other community members resolved these concerns and often resulted in interest and acceptance among peers. CONCLUSION: Objective monitoring of bednet use with SmartNet appears acceptable to these households in Uganda. Use of SmartNet seems to be similar to behaviors around use of standard LLINs. Viewpoints on many aspects of SmartNet were generally favorable. Concerns around ethicality of bednet monitoring are present and indicate the need for continuing community education. The device will continue to be optimized to make it more acceptable to users and to accurately reflect standard LLIN use to improve our understanding of prevention behaviors in malaria endemic settings.
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Mosquiteros Tratados con Insecticida , Malaria , Estudios Transversales , Electrónica , Humanos , Malaria/epidemiología , Malaria/prevención & control , Control de Mosquitos , UgandaRESUMEN
BACKGROUND: Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator and mild bronchodilator that has been shown to improve systemic oxygenation, but has rarely been administered in the Emergency Department (ED). In addition to its favorable pulmonary vascular effects, in-vitro studies report that NO donors can inhibit replication of viruses, including SARS Coronavirus 2 (SARS-CoV-2). This study evaluated the administration of high-dose iNO by mask in spontaneously breathing emergency department (ED) patients with respiratory symptoms attributed to Coronavirus disease 2019 (COVID-19). METHODS: We designed a randomized clinical trial to determine whether 30 min of high dose iNO (250 ppm) could be safely and practically administered by emergency physicians in the ED to spontaneously-breathing patients with respiratory symptoms attributed to COVID-19. Our secondary goal was to learn if iNO could prevent the progression of mild COVID-19 to a more severe state. FINDINGS: We enrolled 47 ED patients with acute respiratory symptoms most likely due to COVID-19: 25 of 47 (53%) were randomized to the iNO treatment group; 22 of 47 (46%) to the control group (supportive care only). All patients tolerated the administration of high-dose iNO in the ED without significant complications or symptoms. Five patients receiving iNO (16%) experienced asymptomatic methemoglobinemia (MetHb) > 5%. Thirty-four of 47 (72%) subjects tested positive for SARS-CoV-2: 19 of 34 were randomized to the iNO treatment group and 15 of 34 subjects to the control group. Seven of 19 (38%) iNO patients returned to the ED, while 4 of 15 (27%) control patients did. One patient in each study arm was hospitalized: 5% in iNO treatment and 7% in controls. One patient was intubated in the iNO group. No patients in either group died. The differences between these groups were not significant. CONCLUSION: A single dose of iNO at 250 ppm was practical and not associated with any significant adverse effects when administered in the ED by emergency physicians. Local disease control led to early study closure and prevented complete testing of COVID-19 safety and treatment outcomes measures.
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COVID-19 , Insuficiencia Respiratoria , Administración por Inhalación , Servicio de Urgencia en Hospital , Humanos , Óxido Nítrico/uso terapéutico , Insuficiencia Respiratoria/terapia , SARS-CoV-2RESUMEN
Nitric oxide (NO) activity in vivo is the combined results of its direct effects, the action of its derivatives generated from NO autoxidation, and the effects of nitrosated compounds. Measuring NO metabolites is essential to studying NO activity both at vascular levels and in other tissues, especially in the experimental settings where exogenous NO is administered. Ozone-based chemiluminescence assays allow precise measurements of NO and NO metabolites in both fluids (including plasma, tissue homogenates, cell cultures) and gas mixtures (e.g., exhaled breath). NO reacts with ozone to generate nitrogen dioxide in an excited state. The consequent light emission allows photodetection and the generation of an electric signal reflecting the NO content of the sample. Aliquots from the same sample can be used to measure specific NO metabolites, such as nitrate, nitrite, S-nitrosothiols, and iron-nitrosyl complexes. In addition, NO consumed by cell-free hemoglobin is also quantified with chemiluminescence analysis. An illustration of all these techniques is provided.
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Luminiscencia , Óxido Nítrico , Mediciones Luminiscentes/métodos , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismoRESUMEN
The global COVID-19 pandemic has become the largest public health challenge of recent years. The incidence of COVID-19-related acute hypoxemic respiratory failure (AHRF) occurs in up to 15% of hospitalized patients. Antiviral drugs currently available to clinicians have little to no effect on mortality, length of in-hospital stay, the need for mechanical ventilation, or long-term effects. Inhaled nitric oxide (iNO) administration is a promising new non-standard approach to directly treat viral burden while enhancing oxygenation. Along with its putative antiviral affect in COVID-19 patients, iNO can reduce inflammatory cell-mediated lung injury by inhibiting neutrophil activation, lowering pulmonary vascular resistance and decreasing edema in the alveolar spaces, collectively enhancing ventilation/perfusion matching. This narrative review article presents recent literature on the iNO therapy use for COVID-19 patients. The authors suggest that early administration of the iNO therapy may be a safe and promising approach for the treatment of COVID-19 patients. The authors also discuss unconventional approaches to treatment, continuous versus intermittent high-dose iNO therapy, timing of initiation of therapy (early versus late), and novel delivery systems. Future laboratory and clinical research is required to define the role of iNO as an adjunct therapy against bacterial, viral, and fungal infections.
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OBJECTIVES: A recent study suggests that Multisystem Inflammatory Syndrome in Children (MIS-C) is triggered by gastrointestinal breach of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral particles from the gut lumen into systemic circulation. The virus remains in the gut weeks to months after respiratory infection, causing zonulin release from the intestinal epithelial cells. Zonulin loosens tight junctions, permitting trafficking of highly inflammatory viral particles into circulation. Current MIS-C treatments target the subsequent immune hyperactivation, not the causative loss of mucosal barrier integrity. Larazotide, a zonulin inhibitor, prevents breakdown of tight junctions, limiting antigen trafficking. DESIGN: Children with MIS-C were treated with larazotide as an adjuvant to steroid/intravenous immunoglobulin therapy. Clinical outcomes, SARS-CoV-2 antigenemia, and cytokine profiles are reported. Outcomes were compared with children with MIS-C receiving steroids and/or IVIG therapy alone. PATIENTS: Four children with MIS-C, ages 3-17 years, were enrolled. INTERVENTIONS: Patients were treated with open label larazotide 10 mcg/kg (maximum 500 mcg/dose) orally four times daily for 21 days. MEASUREMENTS AND MAIN RESULTS: All four patients tolerated larazotide without adverse effects and displayed reduction in Spike antigenemia to undetectable levels. When compared with 22 children with MIS-C receiving steroids and/or intravenous immunoglobulin therapy alone, larazotide-treated patients reported significantly improved time to resolution of gastrointestinal symptoms (p = 0.03), and time to clearance of Spike antigenemia (p = 0.04), plus a trend towards shorter length of stay. CONCLUSIONS: Larazotide appears safe and well-tolerated and may offer potential benefit as an adjuvant to immune-targeted therapies. Expansion of clinical trials is urgently needed to ascertain the clinical impact of larazotide on MIS-C.
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Treatment of multisystem inflammatory syndrome in children (MIS-C) can require significant critical care resources. Our aim is to alert mixed pediatric and adult hospitals worldwide of the possibility that pediatric and adult patients may simultaneously require cannulation to extracorporeal membrane oxygenation (ECMO) for MIS-C and severe COVID-19. We conducted a retrospective review of operations required to treat cardiogenic shock in 3 pediatric patients with a diagnosis of MIS-C admitted to a single medium-sized pediatric referral center located within a large academic medical center over a 14-day period. At this time, a large number of adult patients required ECMO for severe COVID-19 at our institution. Of the 11 pediatric patients who presented with MIS-C during the first surge of 2020, 2 patients required cannulation to venoarterial extracorporeal membrane oxygenation (VA-ECMO), and a third patient developed a life-threatening arrhythmia requiring transfer to a neighboring institution for consideration of VA-ECMO when our institution's ECMO capacity had briefly been reached. Pediatric referral centers located within institutions providing ECMO to adult patients with severe COVID-19 may benefit from frequent and direct communication with their adult and regional colleagues to devise a collaborative plan for safe and timely provision of ECMO to patients with MIS-C as the ongoing pandemic continues to consume this limited, lifesaving resource.
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COVID-19 , Oxigenación por Membrana Extracorpórea , COVID-19/complicaciones , COVID-19/terapia , Niño , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Síndrome de Respuesta Inflamatoria SistémicaRESUMEN
OBJECTIVE: Determine non-invasive ventilation with continuous positive airway pressure (CPAP) outcomes for paediatric respiratory distress in low-income and middle-income countries (LMICs). DESIGN: Systematic review and meta-analysis. SETTING: LMIC hospitals. PATIENTS: One month to 15 year olds with respiratory distress. INTERVENTIONS: We searched Medline, Embase, LILACS, Web of Science and Scopus on 7 April 2020. Included studies assessed CPAP safety, efficacy or effectiveness. All study types were included; neonatal only studies were excluded. Data were extracted by two reviewers and bias was assessed. Certainty of evidence was evaluated, and risk ratios (RR) were produced for meta-analyses. (PROSPERO protocol CRD42018084278). RESULTS: 2174 papers were screened, 20 were included in the systematic review and 3 were included in two separate meta-analyses of mortality and adverse events. Studies suitable for meta-analysis were randomised controlled trials (RCTs) from Bangladesh, Ghana and Malawi. For meta-analyses comparing death or adverse events between CPAP and low-flow oxygen recipients, we found no clear CPAP effect on mortality (RR 0.75, 95% CI 0.33 to 1.72) or adverse events (RR 1.52, CI 0.71 to 3.26). We downgraded the certainty of evidence for both death and adverse events outcomes to 'low' due to design issues and results discrepancies across RCTs. CONCLUSIONS: Evidence for CPAP efficacy against mortality and adverse events has low certainty and is context dependent. Hospitals introducing CPAP need to have mechanisms in place to optimise safety in the context it is being used; this includes the location (a high dependency or intensive care area), adequate numbers of staff trained in CPAP use, close monitoring and mechanisms for escalation, daily direct physician supervision, equipment that is age appropriate and user-friendly and continuous monitoring of outcomes and quality of care.
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Presión de las Vías Aéreas Positiva Contínua , Síndrome de Dificultad Respiratoria , Niño , Presión de las Vías Aéreas Positiva Contínua/efectos adversos , Cuidados Críticos , Humanos , Recién Nacido , Oxígeno , Respiración ArtificialRESUMEN
BACKGROUND: High-dose (≥ 80 ppm) inhaled nitric oxide (INO) has antimicrobial effects. We designed a trial to test the preventive effects of high-dose NO on coronavirus disease 2019 (COVID-19) in health care providers working with patients with COVID-19. The study was interrupted prematurely due to the introduction of COVID-19 vaccines for health care professionals. We thereby present data on safety and feasibility of breathing 160 ppm NO using 2 different NO sources, namely pressurized nitrogen/NO cylinders (INO) and electric NO (eNO) generators. METHODS: NO gas was inhaled at 160 ppm in air for 15 min twice daily, before and after each work shift, over 14 d by health care providers (NCT04312243). During NO administration, vital signs were continuously monitored. Safety was assessed by measuring transcutaneous methemoglobinemia (SpMet) and the inhaled nitrogen dioxide (NO2) concentration. RESULTS: Twelve healthy health care professionals received a collective total of 185 administrations of high-dose NO (160 ppm) for 15 min twice daily. One-hundred and seventy-one doses were delivered by INO and 14 doses by eNO. During NO administration, SpMet increased similarly in both groups (P = .82). Methemoglobin decreased in all subjects at 5 min after discontinuing NO administration. Inhaled NO2 concentrations remained between 0.70 ppm (0.63-0.79) and 0.75 ppm (0.67-0.83) in the INO group and between 0.74 ppm (0.68-0.78) and 0.88 ppm (0.70-0.93) in the eNO group. During NO administration, peripheral oxygen saturation and heart rate did not change. No adverse events occurred. CONCLUSIONS: This pilot study testing high-dose INO (160 ppm) for 15 min twice daily using eNO seems feasible and similarly safe when compared with INO.
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COVID-19 , Óxido Nítrico , Administración por Inhalación , Vacunas contra la COVID-19 , Humanos , Saturación de Oxígeno , Proyectos Piloto , SARS-CoV-2RESUMEN
BACKGROUND: Inhaled nitric oxide (NO) is a selective pulmonary vasodilator. In-vitro studies report that NO donors can inhibit replication of SARS-CoV-2. This multicenter study evaluated the feasibility and effects of high-dose inhaled NO in non-intubated spontaneously breathing patients with Coronavirus disease-2019 (COVID-19). METHODS: This is an interventional study to determine whether NO at 160 parts-per-million (ppm) inhaled for 30 min twice daily might be beneficial and safe in non-intubated COVID-19 patients. RESULTS: Twenty-nine COVID-19 patients received a total of 217 intermittent inhaled NO treatments for 30 min at 160 ppm between March and June 2020. Breathing NO acutely decreased the respiratory rate of tachypneic patients and improved oxygenation in hypoxemic patients. The maximum level of nitrogen dioxide delivered was 1.5 ppm. The maximum level of methemoglobin (MetHb) during the treatments was 4.7%. MetHb decreased in all patients 5 min after discontinuing NO administration. No adverse events during treatment, such as hypoxemia, hypotension, or acute kidney injury during hospitalization occurred. In our NO treated patients, one patient of 29 underwent intubation and mechanical ventilation, and none died. The median hospital length of stay was 6 days [interquartile range 4-8]. No discharged patients required hospital readmission nor developed COVID-19 related long-term sequelae within 28 days of follow-up. CONCLUSIONS: In spontaneous breathing patients with COVID-19, the administration of inhaled NO at 160 ppm for 30 min twice daily promptly improved the respiratory rate of tachypneic patients and systemic oxygenation of hypoxemic patients. No adverse events were observed. None of the subjects was readmitted or had long-term COVID-19 sequelae.
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Tratamiento Farmacológico de COVID-19 , Hospitalización , Óxido Nítrico/administración & dosificación , Neumonía Viral/tratamiento farmacológico , Respiración/efectos de los fármacos , Administración por Inhalación , COVID-19/complicaciones , COVID-19/virología , Relación Dosis-Respuesta a Droga , Humanos , Óxido Nítrico/farmacología , Óxido Nítrico/uso terapéutico , Neumonía Viral/complicacionesRESUMEN
BACKGROUND: Pneumonia is a leading cause of sepsis and mortality in children under 5 years. However, our understanding of the causes of bacteremia in children with pneumonia is limited. METHODS: We characterized risk factors for bacteremia and death in a cohort of children admitted to the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b) between 2014 and 2017 with radiographically confirmed pneumonia. RESULTS: A total of 4007 young children were hospitalized with pneumonia over the study period. A total of 1814 (45%) had blood cultures obtained. Of those, 108 (6%) were positive. Gram-negative pathogens predominated, accounting for 83 (77%) of positive cultures. These included Pseudomonas (Nâ =â 22), Escherichia coli (Nâ =â 17), Salmonella enterica (Nâ =â 14, including 11 Salmonella Typhi), and Klebsiella pneumoniae (Nâ =â 11). Gram-positive pathogens included Pneumococcus (Nâ =â 7) and Staphylococcus aureus (Nâ =â 6). Resistance to all routinely used empiric antibiotics (ampicillin, gentamicin, ciprofloxacin, and ceftriaxone) for children with pneumonia at the icddr,b was observed in 20 of the 108 isolates. Thirty-one of 108 (29%) children with bacteremia died, compared to 124 of 1706 (7%) who underwent culture without bacteremia (odds ratio [OR], 5.1; 95% confidence interval [CI], 3.3-8.1; Pâ <â .001). Children infected with bacteria resistant to all routinely used empiric antibiotics were at greater risk of death compared to children without bacteremia (OR, 17.3; 95% CI, 7.0-43.1; Pâ <â .001). CONCLUSIONS: Antibiotic-resistant Gram-negative bacteremia in young children with pneumonia in Dhaka, Bangladesh was associated with a high mortality rate. The pandemic of antibiotic resistance is shortening the lives of young children in Bangladesh, and new approaches to prevent and treat these infections are desperately needed.
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Importance: Multisystem inflammatory syndrome in children (MIS-C) is associated with recent or current SARS-CoV-2 infection. Information on MIS-C incidence is limited. Objective: To estimate population-based MIS-C incidence per 1â¯000â¯000 person-months and to estimate MIS-C incidence per 1â¯000â¯000 SARS-CoV-2 infections in persons younger than 21 years. Design, Setting, and Participants: This cohort study used enhanced surveillance data to identify persons with MIS-C during April to June 2020, in 7 jurisdictions reporting to both the Centers for Disease Control and Prevention national surveillance and to Overcoming COVID-19, a multicenter MIS-C study. Denominators for population-based estimates were derived from census estimates; denominators for incidence per 1â¯000â¯000 SARS-CoV-2 infections were estimated by applying published age- and month-specific multipliers accounting for underdetection of reported COVID-19 case counts. Jurisdictions included Connecticut, Georgia, Massachusetts, Michigan, New Jersey, New York (excluding New York City), and Pennsylvania. Data analyses were conducted from August to December 2020. Exposures: Race/ethnicity, sex, and age group (ie, ≤5, 6-10, 11-15, and 16-20 years). Main Outcomes and Measures: Overall and stratum-specific adjusted estimated MIS-C incidence per 1â¯000â¯000 person-months and per 1â¯000â¯000 SARS-CoV-2 infections. Results: In the 7 jurisdictions examined, 248 persons with MIS-C were reported (median [interquartile range] age, 8 [4-13] years; 133 [53.6%] male; 96 persons [38.7%] were Hispanic or Latino; 75 persons [30.2%] were Black). The incidence of MIS-C per 1â¯000â¯000 person-months was 5.1 (95% CI, 4.5-5.8) persons. Compared with White persons, incidence per 1â¯000â¯000 person-months was higher among Black persons (adjusted incidence rate ratio [aIRR], 9.26 [95% CI, 6.15-13.93]), Hispanic or Latino persons (aIRR, 8.92 [95% CI, 6.00-13.26]), and Asian or Pacific Islander (aIRR, 2.94 [95% CI, 1.49-5.82]) persons. MIS-C incidence per 1â¯000â¯000 SARS-CoV-2 infections was 316 (95% CI, 278-357) persons and was higher among Black (aIRR, 5.62 [95% CI, 3.68-8.60]), Hispanic or Latino (aIRR, 4.26 [95% CI, 2.85-6.38]), and Asian or Pacific Islander persons (aIRR, 2.88 [95% CI, 1.42-5.83]) compared with White persons. For both analyses, incidence was highest among children aged 5 years or younger (4.9 [95% CI, 3.7-6.6] children per 1â¯000â¯000 person-months) and children aged 6 to 10 years (6.3 [95% CI, 4.8-8.3] children per 1â¯000â¯000 person-months). Conclusions and Relevance: In this cohort study, MIS-C was a rare complication associated with SARS-CoV-2 infection. Estimates for population-based incidence and incidence among persons with infection were higher among Black, Hispanic or Latino, and Asian or Pacific Islander persons. Further study is needed to understand variability by race/ethnicity and age group.
Asunto(s)
COVID-19/epidemiología , Síndrome de Respuesta Inflamatoria Sistémica/epidemiología , Adolescente , Distribución por Edad , Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Incidencia , Masculino , Grupos Raciales/estadística & datos numéricos , SARS-CoV-2 , Estados Unidos/epidemiología , Adulto JovenRESUMEN
Nitric oxide (NO) is a biologically active molecule approved for the treatment of pulmonary hypertension in newborn patients. Commercially available NO delivery systems use pressurized cylinders as the source of NO and a sensor to control the concentrations of NO and nitrogen dioxide (NO2) delivered. Cylinder-based delivery systems are safe and widely used around the world, but they are bulky, expensive, and reliant on a robust supply chain. In the past few years, novel NO generators and delivery systems have been developed to overcome these limitations. Electric NO generators produce NO from ambient air using high-voltage electrical discharge to ionize air, which leads to the formation of NO, NO2, and ozone (O3). A scavenging system is incorporated to reduce the concentration of the toxic byproducts generated in this type of system. NO can also be generated by the reduction of NO2 by ascorbic acid or released from liquid solutions or solid nanoparticles. The development of easy-to-use, safe, and portable NO delivery systems may enable the delivery of NO in the out-patient setting or at home. Furthermore, non-cylinder-based NO generators reduce the cost of NO production and storage and may therefore make NO delivery feasible in low-resource settings. Here we review commercially available systems that can generate and administer inhalable NO.