Added Value of a Robotic-assisted Bronchoscopy Platform in Cone Beam Computed Tomography-guided Bronchoscopy for the Diagnosis of Pulmonary Parenchymal Lesions.

BACKGROUND: Cone beam computed tomography (CBCT)-guided bronchoscopic sampling of peripheral pulmonary lesions (PPLs) is associated with superior diagnostic outcomes. However, the added value of a robotic-assisted bronchoscopy platform in CBCT-guided diagnostic procedures is unknown. METHODS: We performed a retrospective review of 100 consecutive PPLs sampled using conventional flexible bronchoscopy under CBCT guidance (FB-CBCT) and 100 consecutive PPLs sampled using an electromagnetic navigation-guided robotic-assisted bronchoscopy platform under CBCT guidance (RB-CBCT). Patient demographics, PPL features, procedural characteristics, and procedural outcomes were compared between the 2 cohorts. RESULTS: Patient and PPL characteristics were similar between the FB-CBCT and RB-CBCT cohorts, and there were no significant differences in diagnostic yield (88% vs. 90% for RB-CBCT, P=0.822) or incidence of complications between the 2 groups. As compared with FB-CBCT cases, RB-CBCT cases were significantly shorter (median 58 min vs. 92 min, P<0.0001) and used significantly less diagnostic radiation (median dose area product 5114 µGy•m2 vs. 8755 µGy•m2, P<0.0001). CONCLUSION: CBCT-guided bronchoscopy with or without a robotic-assisted bronchoscopy platform is a safe and effective method for sampling PPLs, although the integration of a robotic-assisted platform was associated with significantly shorter procedure times and significantly less radiation exposure.

Immediate and Follow-up Imaging Findings after Cone-Beam CT-guided Transbronchial Lung Cryobiopsy.

Purpose: To evaluate findings after transbronchial lung cryobiopsy (TBLC) using intraprocedural cone-beam CT (CBCT) and follow-up chest CT examinations. Materials and Methods: A single-center, prospective cohort study was performed with 14 participants (mean age, 65 years ± 13 [SD]; eight male participants) undergoing CBCT-guided TBLC between August 2020 and February 2021 who underwent follow-up chest CT imaging. Intraprocedural CBCT and follow-up chest CT images were interpreted for changes compared with baseline CT images. Statistical analyses were performed using independent samples t test and analysis of variance. Results: A total of 62 biopsies were performed, with 48 in the field of view of CBCT immediately after biopsy. All 48 biopsy sites had evidence of postprocedural hemorrhage, and 17 (35%) had pneumatoceles at the biopsy site. Follow-up CT images showed resolution of these findings. Solid nodules developed at 18 of the 62 (29%) biopsy sites. Conclusion: Postbiopsy hemorrhage and pneumatoceles on intraprocedural CBCT images (which were clinically occult and resolved spontaneously) and new solid nodules on follow-up chest CT images were commonly observed after TBLC. These findings may help alleviate unnecessary follow-up imaging and tissue sampling.Keywords: Biopsy/Needle Aspiration, CT, Lungs, Lung Biopsy, Interventional Bronchoscopy© RSNA, 2023.

Pathophysiology of Hypoxemia in COVID-19 Lung Disease.

As the pandemic has progressed, our understanding of hypoxemia in coronavirus disease 2019 (COVID-19) lung disease has become more nuanced, although much remains to be understood. In this article, we review ventilation-perfusion mismatching in COVID-19 and the evidence to support various biologic theories offered in explanation. In addition, the relationship between hypoxemia and other features of severe COVID-19 lung disease such as respiratory symptoms, radiographic abnormalities, and pulmonary mechanics is explored. Recognizing and understanding hypoxemia in COVID-19 lung disease remains essential for risk stratification, prognostication, and choice of appropriate treatments in severe COVID-19.

Performance and reliability of two frequently used point-of-care blood gas analyzers at 423 and 4,559 m.

BACKGROUND AND OBJECTIVES: Blood gas analyzers (BGA) aid medical decision-making. Their specified performance criteria are based on sea level conditions. However, millions of people are living at high altitude (HA) where the performance of BGAs is poorly characterized. We investigated the effect of exposure to 4,559 m on the reliability and robustness of two BGAs widely used at HA. METHODS: In this prospective study arterial blood samples from 13 volunteers (2 female) with susceptibility to the development of high-altitude pulmonary edema were collected once near sea level at 423 m (nSL423) and three times at high altitude (HA4,559). Samples were measured in triplicate with the cartridge BGAs Rapidpoint 500 (SIE; Siemens Healthcare) and the ABL90 (RAD; Radiometer) to calculate coefficients of variation (CV) and intraclass correlation coefficients (ICC) within a mixed model. RESULTS: At nSL423 and HA4,559, 3% and 17% of all data were not reported with SIE, mainly due to clotting of the sample caused by delays because of the frequent automated calibration routines. No data were missing with RAD. ICCs were not significantly lower (mean (min-max) 0.87 (0.68-0.98) vs. 0.94 (0.84-1.00); p = 0.217) with SIE at nSL423, but significantly lower at HA4,559 (0.87 (0.49-1.00) vs. 0.99 (0.96-1.00); p = 0.025). All CVs, except that for arterial oxygen saturation at HA4,559,were higher with SIE . CONCLUSION: In this study, the reliability of RAD was superior to SIE at nSL423 and HA4,559. In contrast to RAD, the performance of SIE declined at HA4,559. SIE was more prone to not reporting all variables, especially at HA4559.

Oxygen Therapy Part 1 - History, Physiology, and Evaluation.

History, Physiology, and Evaluation of Oxygen TherapyOxygen is standard therapy for acute cardiopulmonary diseases, and long-term oxygen therapy is common in the outpatient setting. In part I of a two-part review, Wemple and colleagues discuss the physiology of tissue hypoxia, mechanisms of hypoxemia, and its clinical assessment.

Oxygen Therapy Part 2 - Indications and Toxicity.

Oxygen Therapy Part 2: Indications and ToxicityWemple et al. continue their review of oxygen therapy, discussing the acute and chronic indications for oxygen and the delivery of supplemental oxygen (and its potential adverse effects and toxicity).

Effects of acetazolamide on pulmonary artery pressure and prevention of high-altitude pulmonary edema after rapid active ascent to 4,559 m.

Acetazolamide prevents acute mountain sickness (AMS) by inhibition of carbonic anhydrase. Since it also reduces acute hypoxic pulmonary vasoconstriction (HPV), it may also prevent high-altitude pulmonary edema (HAPE) by lowering pulmonary artery pressure. We tested this hypothesis in a randomized, placebo-controlled, double-blind study. Thirteen healthy, nonacclimatized lowlanders with a history of HAPE ascended (<22 h) from 1,130 to 4,559 m with one overnight stay at 3,611 m. Medications were started 48 h before ascent (acetazolamide: n = 7, 250 mg 3 times/day; placebo: n = 6, 3 times/day). HAPE was diagnosed by chest radiography and pulmonary artery pressure by measurement of right ventricular to atrial pressure gradient (RVPG) by transthoracic echocardiography. AMS was evaluated with the Lake Louise Score (LLS) and AMS-C score. The incidence of HAPE was 43% versus 67% (acetazolamide vs. placebo, P = 0.39). Ascent to altitude increased RVPG from 20 ± 5 to 43 ± 10 mmHg (P < 0.001) without a group difference (P = 0.68). Arterial Po2 fell to 36 ± 9 mmHg (P < 0.001) and was 8.5 mmHg higher with acetazolamide at high altitude (P = 0.025). At high altitude, the LLS and AMS-C score remained lower in those taking acetazolamide (both P < 0.05). Although acetazolamide reduced HAPE incidence by 35%, this effect was not statistically significant, and was considerably less than reductions of about 70%-100% with prophylactic dexamethasone, tadalafil, and nifedipine performed with the same ascent profile at the same location. We could not demonstrate a reduction in RVPG compared with placebo treatment despite reductions in AMS severity and better arterial oxygenation. Limited by small sample size, our data do not support recommending acetazolamide for the prevention of HAPE in mountaineers ascending rapidly to over 4,500 m.NEW & NOTEWORTHY This randomized, placebo-controlled, double-blind study is the first to investigate whether acetazolamide, which reduces acute mountain sickness (AMS), inhibits short-term hypoxic pulmonary vasoconstriction, and also prevents high-altitude pulmonary edema (HAPE) in a fast-climbing ascent to 4,559 m. We found no statistically significant reduction in HAPE incidence or differences in hypoxic pulmonary artery pressures compared with placebo despite reductions in AMS and greater ventilation-induced arterial oxygenation. Our data do not support recommending acetazolamide for HAPE prevention.

Validity of Peripheral Oxygen Saturation Measurements with the Garmin Fenix® 5X Plus Wearable Device at 4559 m.

Decreased oxygen saturation (SO2) at high altitude is associated with potentially life-threatening diseases, e.g., high-altitude pulmonary edema. Wearable devices that allow continuous monitoring of peripheral oxygen saturation (SpO2), such as the Garmin Fenix® 5X Plus (GAR), might provide early detection to prevent hypoxia-induced diseases. We therefore aimed to validate GAR-derived SpO2 readings at 4559 m. SpO2 was measured with GAR and the medically certified Covidien Nellcor SpO2 monitor (COV) at six time points in 13 healthy lowlanders after a rapid ascent from 1130 m to 4559 m. Arterial blood gas (ABG) analysis served as the criterion measure and was conducted at four of the six time points with the Radiometer ABL 90 Flex. Validity was assessed by intraclass correlation coefficients (ICCs), mean absolute percentage error (MAPE), and Bland-Altman plots. Mean (±SD) SO2, including all time points at 4559 m, was 85.2 ± 6.2% with GAR, 81.0 ± 9.4% with COV, and 75.0 ± 9.5% with ABG. Validity of GAR was low, as indicated by the ICC (0.549), the MAPE (9.77%), the mean SO2 difference (7.0%), and the wide limits of agreement (-6.5; 20.5%) vs. ABG. Validity of COV was good, as indicated by the ICC (0.883), the MAPE (6.15%), and the mean SO2 difference (0.1%) vs. ABG. The GAR device demonstrated poor validity and cannot be recommended for monitoring SpO2 at high altitude.

The Pathophysiology and Dangers of Silent Hypoxemia in COVID-19 Lung Injury.

The ongoing coronavirus disease (COVID-19) pandemic has been unprecedented on many levels, not least of which are the challenges in understanding the pathophysiology of these new critically ill patients. One widely reported phenomenon is that of a profoundly hypoxemic patient with minimal to no dyspnea out of proportion to the extent of radiographic abnormality and change in lung compliance. This apparently unique presentation, sometimes called "happy hypoxemia or hypoxia" but better described as "silent hypoxemia," has led to the speculation of underlying pathophysiological differences between COVID-19 lung injury and acute respiratory distress syndrome (ARDS) from other causes. We explore three proposed distinctive features of COVID-19 that likely bear on the genesis of silent hypoxemia, including differences in lung compliance, pulmonary vascular responses to hypoxia, and nervous system sensing and response to hypoxemia. In the context of known principles of respiratory physiology and neurobiology, we discuss whether these particular findings are due to direct viral effects or, equally plausible, are within the spectrum of typical ARDS pathophysiology and the wide range of hypoxic ventilatory and pulmonary vascular responses and dyspnea perception in healthy people. Comparisons between lung injury patterns in COVID-19 and other causes of ARDS are clouded by the extent and severity of this pandemic, which may underlie the description of "new" phenotypes, although our ability to confirm these phenotypes by more invasive and longitudinal studies is limited. However, given the uncertainty about anything unique in the pathophysiology of COVID-19 lung injury, there are no compelling pathophysiological reasons at present to support a therapeutic approach for these patients that is different from the proven standards of care in ARDS.

Systemic arterial gas embolism (SAGE) as a complication of bronchoscopic lung biopsy: a case report and systematic literature review.

BACKGROUND: Systemic arterial gas embolism (SAGE) is a rare yet serious and underrecognized complication of bronchoscopic procedures. A recent case of presumed SAGE after transbronchial needle aspiration prompted a systematic literature review of SAGE after biopsy procedures during flexible bronchoscopy. METHODS: We performed a systematic database search for case reports and case series pertaining to SAGE after bronchoscopic lung biopsy; reports or series involving only bronchoscopic laser therapy or argon plasma coagulation (APC) were excluded. Patient data were extracted directly from published reports. RESULTS: A total of 29 unique patient reports were assessed for patient demographics, specifics of the procedure, clinical manifestations, diagnostic findings, and clinical outcomes. Cases of SAGE occurred after multiple types of bronchoscopic biopsy and under both positive and negative pressure ventilation. The most common clinical findings were neurologic, followed by cardiac manifestations; temporal patterns included acute onset of cardiac or neurologic emergencies immediately after biopsy, or delayed awakening post-procedure. There was a high mortality rate among cases (28%), with residual neurologic deficits also common (24%). DISCUSSION: SAGE is an underrecognized but severe adverse effect of bronchoscopic lung biopsy, which often presents with acute coronary or cerebral ischemia or delayed awakening from sedation. It is important for all physicians who perform bronchoscopic biopsies to be aware of the clinical manifestations and therapeutic management of SAGE in order to mitigate morbidity and mortality among patients undergoing these procedures.

Impact of Sepsis Mandates on Sepsis Care: Unintended Consequences.

The creation of dedicated sepsis guidelines and their broad dissemination over the past 2 decades have contributed to significant improvements in sepsis care. These successes have spurred the creation of bundled care mandates by major healthcare payers, such as the Center for Medicare and Medicaid Services. However, despite the likely benefits of guideline-directed sepsis bundles, mandated treatments in sepsis may lead to unintended consequences as the standard of care in sepsis improves. In particular, the heterogeneous spectrum of presentation and disease severity in sepsis, as well as the complexity surrounding the benefits of specific interventions in sepsis, argues for an individualized and titrated approach to interventions: an approach generally not afforded by care mandates. In this review, we review the risks and benefits of mandated care for sepsis, with particular emphasis on the potential adverse consequences of common bundle components such as early empiric antibiotics, weight-based fluid administration, and serum lactate monitoring. Unlike guideline-directed care, mandated care in sepsis precludes providers from tailoring treatments to heterogeneous clinical scenarios and may lead to unintended harms for individual patients.

Evaluation of a novel 5-group classification system of sepsis by vasopressor use and initial serum lactate in the emergency department.

Prognostication in sepsis is limited by disease heterogeneity, and measures to risk-stratify patients in the proximal phases of care lack simplicity and accuracy. Hyperlactatemia and vasopressor dependence are easily identifiable risk factors for poor outcomes. This study compares incidence and hospital outcomes in sepsis based on initial serum lactate level and vasopressor use in the emergency department (ED). In a retrospective analysis of a prospectively identified dual-center ED registry, patients with sepsis were categorized by ED vasopressor use and initial serum lactate level. Vasopressor-dependent patients were categorized as dysoxic shock (lactate >4.0 mmol/L) and vasoplegic shock (≤4.0 mmol/L). Patients not requiring vasopressors were categorized as cryptic shock major (lactate >4.0 mmol/L), cryptic shock minor (>2.0 and ≤4.0 mmol/L), and sepsis without lactate elevation (≤2.0 mmol/L). Of 446 patients included, 4.9% (n = 22) presented in dysoxic shock, 11.7% (n = 52) in vasoplegic shock, 12.1% (n = 54) in cryptic shock major, 30.9% (n = 138) in cryptic shock minor, and 40.4% (n = 180) in sepsis without lactate elevation. Group mortality rates at 28 days were 50.0, 21.1, 18.5, 12.3, and 7.2%, respectively. After adjusting for potential confounders, odds ratios for mortality at 28 days were 15.1 for dysoxic shock, 3.6 for vasoplegic shock, 3.8 for cryptic shock major, and 1.9 for cryptic shock minor, when compared to sepsis without lactate elevation. Lactate elevation is associated with increased mortality in both vasopressor dependent and normotensive infected patients presenting to the emergency department (ED). Cryptic shock mortality (normotension + lactate >4 mmol/L) is equivalent to vasoplegic shock mortality (vasopressor requirement + lactate <4 mmol/L) in our population. The odds of normotensive, infected patients decompensating is three to fourfold higher with hyperlactemia. The proposed Sepsis-3 definitions exclude an entire group of high-risk ED patients. A simple classification in the ED by vasopressor requirement and initial lactate level may identify high-risk subgroups of sepsis. This study may inform prognostication and triage decisions in the proximal phases of care.

Acetazolamide and N-acetylcysteine in the treatment of chronic mountain sickness (Monge's disease).

Patients suffering from chronic mountain sickness (CMS) have excessive erythrocytosis. Low -level cobalt toxicity as a likely contributor has been demonstrated in some subjects. We performed a randomized, placebo controlled clinical trial in Cerro de Pasco, Peru (4380m), where 84 participants with a hematocrit (HCT) ≥65% and CMS score>6, were assigned to four treatment groups of placebo, acetazolamide (ACZ, which stimulates respiration), N-acetylcysteine (NAC, an antioxidant that chelates cobalt) and combination of ACZ and NAC for 6 weeks. The primary outcome was change in hematocrit and secondary outcomes were changes in PaO2, PaCO2, CMS score, and serum and urine cobalt concentrations. The mean (±SD) hematocrit, CMS score and serum cobalt concentrations were 69±4%, 9.8±2.4 and 0.24±0.15µg/l, respectively for the 66 participants. The ACZ arm had a relative reduction in HCT of 6.6% vs. 2.7% (p=0.048) and the CMS score fell by 34.9% vs. 14.8% (p=0.014) compared to placebo, while the reduction in PaCO2 was 10.5% vs. an increase of 0.6% (p=0.003), with a relative increase in PaO2 of 13.6% vs. 3.0%. NAC reduced CMS score compared to placebo (relative reduction of 34.0% vs. 14.8%, p=0.017), while changes in other parameters failed to reach statistical significance. The combination of ACZ and NAC was no better than ACZ alone. No changes in serum and urine cobalt concentrations were seen within any treatment arms. ACZ reduced polycythemia and CMS score, while NAC improved CMS score without significantly lowering hematocrit. Only a small proportion of subjects had cobalt toxicity, which may relate to the closing of contaminated water sources and several other environmental protection measures.