Arterial Oxygen Saturation: A Vital Sign?

ABSTRACT: The physical examination is a key part of a continuum that extends from the history of the present illness to the therapeutic outcome. An understanding of the pathophysiological mechanism behind a physical sign is essential for arriving at the correct diagnosis. Early detection of deteriorating physical/vital signs and their appropriate interpretation is thus the key to achieve correct and timely management. By definition, vital signs are "the signs of life that may be monitored or measured, namely pulse rate, respiratory rate, body temperature, and blood pressure." Vital signs are the simplest, cheapest and probably the most inexpensive information gathered bedside in outpatient or hospitalized patients. The pulse oximeter was introduced in the 1980s. It is an accurate and non-invasive method for the measurement of arterial hemoglobin oxygen saturation (SaO2). Pulse oximetry-based arterial oxygen saturation can be effectively used bedside in in-hospital and ambulatory patients with diagnosed or suspected lung disease. The present pandemic of COVID-19 should be considered as a wake-up call. Articles related to arterial oxygen saturation and its importance as a vital sign in patient care were searched online especially in PubMed. Available studies were studied in full length and data was extracted. Discussion: A. Clinical Utility of Oxygen Saturation Monitoring: There are many studies reporting the clinical applicability and usefulness of pulse oximetry in the early detection of hypoxemic events during intraoperative and postoperative periods. B. Role of clinical expertise accompanied by knowledge of physiology: A diagnostic sign is useful only if it is interpreted accurately and applied appropriately while evaluating a patient. The World Health Organisation also appreciates these facts and published "The WHO Pulse Oximetry Training Manual." Understanding the physiology behind and overcoming limitations of the diagnostic sign by clinical expertise is important. While using pulse oximetry, a clinician needs to keep in mind the sigmoidal nature of the oxygen-Hb dissociation curve. Considering these benefits of SaO2 measurement, there have been several references in the past to consider oxygen saturation as the fifth vital sign. In the present pandemic oxygen saturation i.e., SpO2 (arterial oxygen saturation) measured by pulse oxymeter, has been the single most important warning and prognostic sign be it for households, offices, street vendors, hospitals or governments. Measurement of trends of SaO2 added with respiratory rate will provide clinicians with a holistic overview of respiratory functions and multidimensional conditions associated with hypoxemia.

Effects of moderate-intensity intermittent hypoxic training on health outcomes of patients recovered from COVID-19: the AEROBICOVID study protocol for a randomized controlled trial.

BACKGROUND: Recent studies point to a lower number and reduced severity of cases in higher altitude cities with decreased oxygen concentration. Specific literature has shown several benefits of physical training, so, in this sense, physical training with hypoxic stimulus appears as an alternative that supports the conventional treatments of the COVID-19 patient's recovery. Thus, this study's primary aim is to analyze the effects of moderate-intensity intermittent hypoxic training on health outcomes in COVID-19 recovered patients. METHODS: A clinical trial controlled double-blind study was designed. Participants (30-69 years old) will be recruited among those with moderate to severe COVID-19 symptoms, approximately 30 days after recovery. They will be included in groups according to the training (T) and recovery (R) association with hypoxia (H) or normoxia (N): (a) TH:RH, (b) TN:RH, (c) TN:RN, and last (d) the control group. The 8-week exercise bike intervention will be carried out with a gradual load increase according to the established periods, three times a week in sets of 5 min, 90 to 100% of the anaerobic threshold (AT), and a 2.5-min break. Blood will be collected for genotyping. First, after 4 weeks (partial), after 8 weeks, and later, 4 weeks after the end of the physical training intervention, participants will perform assessments. The primary outcome is the maximum oxygen consumption (VO2peak). The secondary outcomes include lung function, inflammatory mediators, hematological, autonomic parameters, AT, body composition analysis, quality of life, mental health, anthropometric measurements, and physical fitness. The statistical analysis will be executed using the linear regression model with mixed effects at a 5% significance level. DISCUSSION: This study is designed to provide evidence to support the clinical benefits of moderate-intensity intermittent hypoxic training as a part of the treatment of patients recovered from COVID-19. It may also provide evidence on the efficacy and safety of intermittent hypoxic training in different health conditions. Lastly, this study presents an innovative strategy enabling up to 16 participants in the same training session. TRIAL REGISTRATION: ClinicalTrials.gov RBR-5d7hkv. Registered after the start of inclusion on 3 November 2020 with the Brazilian Clinical Trials Registry.

Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea.

Nocturnal hypoxemic burden is established as a robust prognostic metric of sleep-disordered breathing (SDB) to predict mortality and treating hypoxemic burden may improve prognosis. The aim of this study was to evaluate improvements in nocturnal hypoxemic burden using transvenous phrenic nerve stimulation (TPNS) to treat patients with central sleep apnea (CSA). The remede System Pivotal Trial population was examined for nocturnal hypoxemic burden. The minutes of sleep with oxygen saturation < 90% significantly improved in Treatment compared with control (p < .001), with the median improving from 33 min at baseline to 14 min at 6 months. Statistically significant improvements were also observed for average oxygen saturation and lowest oxygen saturation. Hypoxemic burden has been demonstrated to be more predictive for mortality than apnea-hypopnea index (AHI) and should be considered a key metric for therapies used to treat CSA. Transvenous phrenic nerve stimulation is capable of delivering meaningful improvements in nocturnal hypoxemic burden. There is increasing interest in endpoints other than apnea-hypopnea index in sleep-disordered breathing. Nocturnal hypoxemia burden may be more predictive for mortality than apnea-hypopnea index in patients with poor cardiac function. Transvenous phrenic nerve stimulation is capable of improving nocturnal hypoxemic burden. Graphical Abstract.

Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia.

A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.

The impact of pulse oximetry and Integrated Management of Childhood Illness (IMCI) training on antibiotic prescribing practices in rural Malawi: A mixed-methods study.

BACKGROUND: The misdiagnosis of non-malarial fever in sub-Saharan Africa has contributed to the significant burden of pediatric pneumonia and the inappropriate use of antibiotics in this region. This study aims to assess the impact of 1) portable pulse oximeters and 2) Integrated Management of Childhood Illness (IMCI) continued education training on the diagnosis and treatment of non-malarial fever amongst pediatric patients being treated by the Global AIDS Interfaith Alliance (GAIA) in rural Malawi. METHODS: This study involved a logbook review to compare treatment patterns between five GAIA mobile clinics in Mulanje, Malawi during April-June 2019. An intervention study design was employed with four study groups: 1) 2016 control, 2) 2019 control, 3) IMCI-only, and 4) IMCI and pulse oximeter. A total of 3,504 patient logbook records were included based on these inclusion criteria: age under five years, febrile, malaria-negative, and treated during the dry season. A qualitative questionnaire was distributed to the participating GAIA providers. Fisher's Exact Testing and odds ratios were calculated to compare the prescriptive practices between each study group and reported with 95% confidence intervals. RESULTS: The pre- and post-exam scores for the providers who participated in the IMCI training showed an increase in content knowledge and understanding (p<0.001). The antibiotic prescription rates in each study group were 75% (2016 control), 85% (2019 control), 84% (IMCI only), and 42% (IMCI + pulse oximeter) (p<0.001). An increase in pneumonia diagnoses was detected for patients who received pulse oximeter evaluation with an oxygen saturation <95% (p<0.001). No significant changes in antibiotic prescribing practices were detected in the IMCI-only group (p>0.001). However, provider responses to the qualitative questionnaires indicated alternative benefits of the training including improved illness classification and increased provider confidence. CONCLUSION: Clinics that implemented both the IMCI course and pulse oximeters exhibited a significant decrease in antibiotic prescription rates, thus highlighting the potential of this tool in combatting antibiotic overconsumption in low-resource settings. Enhanced detection of hypoxia in pediatric patients was regarded by clinicians as helpful for identifying pneumonia cases. GAIA staff appreciated the IMCI continued education training, however it did not appear to significantly impact antibiotic prescription rates and/or pneumonia diagnosis.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.

Australian guidelines for the clinical care of people with COVID-19 - Australian National COVID-19 Clinical Evidence Taskforce

This guideline aims to provide specific, patient-focused recommendations on management and care of people with suspected or confirmed COVID-19. With the exception of chemoprophylaxis for the prevention of infection in people exposed to COVID-19, the guideline does not include other interventions used in the prevention of COVID-19 infection or transmission. Within each recommendation, the patient population of interest is specified.

Mitochondria-targeted Ir@AuNRs as bifunctional therapeutic agents for hypoxia imaging and photothermal therapy.

Ir(iii) complex modified gold nanorods, Ir@AuNRs, were developed as mitochondria-targeted theranostic nanoagents. Their hypoxia imaging and photothermal therapeutic properties were demonstrated in vitro and in vivo.

The association of coffee consumption and oxygen desaturation index during sleep among Japanese male workers.

BACKGROUND AND OBJECTIVE: Coffee is a major caffeine-containing food source that can be used for treatment of apnea in prematurity. However, few studies have examined the association between coffee consumption and sleep-disordered breathing (SDB). We investigated whether coffee consumption is associated with the oxygen desaturation index (ODI) as a marker of SDB among middle-aged Japanese male workers. METHODS: The subjects were 1126 male local government workers aged 22-59 who participated in SDB screening in 2011-2012. Daily coffee consumption was assessed by a self-administered questionnaire. We measured 3% oxygen desaturation (3%ODI) during a night's sleep using a pulse oximeter. A general linear model was used to calculate the multivariate-adjusted means of 3%ODI per quartile of coffee consumption. We further analyzed the data after stratifying by overweight and current smoking status. RESULTS: A inverse association between coffee consumption and 3%ODI was found. The multivariate-adjusted mean of 3%ODI for the lowest and highest coffee consumption groups were 11.9 times/h and 10.6 times/h (p for trend = 0.06), respectively; 14.6 and 11.5 times/h (p for trend = 0.01) in overweight participants; and 12.7 and 11.0 times/h (p for trend = 0.06) in non-smokers. No associations were found in non-overweight and smoking workers. CONCLUSIONS: Our results suggest that higher coffee consumption was associated with lower 3% ODI as a marker of SDB in overweight and non-smoking workers.

Post-Hospitalization Short-Term Oxygen Therapy: Use of a Clinical Management Pathway and Long-Term Follow-Up.

BACKGROUND: Home oxygen therapy is commonly prescribed for patients who remain hypoxemic at hospital discharge, although evidence supporting this practice is lacking. This study aimed to evaluate oxygen prescription and follow-up for patients who were prescribed post-discharge short-term oxygen therapy (STOT) and to assess their long-term outcome. METHODS: A retrospective audit was undertaken of subjects prescribed STOT following hospitalization at a single site in Melbourne, Australia, between January 2011 and December 2015. During the study period, a designated clinical pathway for STOT prescription and follow-up after hospital discharge was in place. Chart review was performed to collect subject demographics and comorbidities, results of oxygen assessment (arterial blood gas and 6-min walk tests) and prescription, and results at follow-up re-assessment and mortality. RESULTS: Over five 5 years, 205 subjects were prescribed STOT upon hospital discharge. Common indications for oxygen treatment were chronic lung disease (54%) and dyspnea palliation (26%). Of the 152 subjects who were discharged with non-palliative oxygen therapy, 28% did not fulfil the recommended prescribing criteria or did not have recommended assessments. Among the 118 subjects who returned for re-assessment 4 weeks after initial oxygen provision, 47 (40%) did not fulfill criteria for long-term oxygen therapy. The 1-y cumulative survival rate for the study population was 56%. CONCLUSIONS: A significant proportion of subjects who were prescribed post-discharge STOT did not fulfill the recommended prescribing criteria. The long-term prognosis for subjects who were prescribed post-discharge STOT was poor.

Hypoxemia following generalized convulsive seizures: Risk factors and effect of oxygen therapy.

OBJECTIVE: To analyze the factors that determine the occurrence or severity of postictal hypoxemia in the immediate aftermath of a generalized convulsive seizure (GCS). METHODS: We reviewed the video-EEG recordings of 1,006 patients with drug-resistant focal epilepsy included in the REPO2MSE study to identify those with ≥1 GCS and pulse oximetry (SpO2) measurement. Factors determining recovery of SpO2 ≥ 90% were investigated using Cox proportional hazards models. Association between SpO2 nadir and person- or seizure-specific variables was analyzed after correction for individual effects and the varying number of seizures. RESULTS: A total of 107 GCS in 73 patients were analyzed. A transient hypoxemia was observed in 92 GCS (86%). Rate of GCS with SpO2 <70% dropped from 40% to 21% when oxygen was administered early (p = 0.046). Early recovery of SpO2 ≥90% was associated with early administration of oxygen (p = 0.004), absence of postictal generalized EEG suppression (PGES) (p = 0.014), and extratemporal lobe epilepsy (p = 0.001). Lack of early administration of O2 (p = 0.003), occurrence of PGES (p = 0.018), and occurrence of ictal hypoxemia during the focal phase (p = 0.022) were associated with lower SpO2 nadir. CONCLUSION: Postictal hypoxemia was observed in the immediate aftermath of nearly all GCS but administration of oxygen had a strong preventive effect. Severity of postictal hypoxemia was greater in temporal lobe epilepsy and when hypoxemia was already observed before the onset of secondary GCS.

Nasal high flow therapy: a novel treatment rather than a more expensive oxygen device.

Nasal high flow is a promising novel oxygen delivery device, whose mechanisms of action offer some beneficial effects over conventional oxygen systems. The administration of a high flow of heated and humidified gas mixture promotes higher and more stable inspiratory oxygen fraction values, decreases anatomical dead space and generates a positive airway pressure that can reduce the work of breathing and enhance patient comfort and tolerance. Nasal high flow has been used as a prophylactic tool or as a treatment device mostly in patients with acute hypoxaemic respiratory failure, with the majority of studies showing positive results. Recently, its clinical indications have been expanded to post-extubated patients in intensive care or following surgery, for pre- and peri-oxygenation during intubation, during bronchoscopy, in immunocompromised patients and in patients with "do not intubate" status. In the present review, we differentiate studies that suggest an advantage (benefit) from other studies that do not suggest an advantage (no benefit) compared to conventional oxygen devices or noninvasive ventilation, and propose an algorithm in cases of nasal high flow application in patients with acute hypoxaemic respiratory failure of almost any cause.

Lateral positioning for critically ill adult patients.

BACKGROUND: Critically ill patients require regular body position changes to minimize the adverse effects of bed rest, inactivity and immobilization. However, uncertainty surrounds the effectiveness of lateral positioning for improving pulmonary gas exchange, aiding drainage of tracheobronchial secretions and preventing morbidity. In addition, it is unclear whether the perceived risk levied by respiratory and haemodynamic instability upon turning critically ill patients outweighs the respiratory benefits of side-to-side rotation. Thus, lack of certainty may contribute to variation in positioning practice and equivocal patient outcomes. OBJECTIVES: To evaluate effects of the lateral position compared with other body positions on patient outcomes (mortality, morbidity and clinical adverse events) in critically ill adult patients. (Clinical adverse events include hypoxaemia, hypotension, low oxygen delivery and global indicators of impaired tissue oxygenation.) We examined single use of the lateral position (i.e. on the right or left side) and repeat use of the lateral position (i.e. lateral positioning) within a positioning schedule. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2015, Issue 5), MEDLINE (1950 to 23 May 2015), the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1937 to 23 May 2015), the Allied and Complementary Medicine Database (AMED) (1984 to 23 May 2015), Latin American Caribbean Health Sciences Literature (LILACS) (1901 to 23 May 2015), Web of Science (1945 to 23 May 2015), Index to Theses in Great Britain and Ireland (1950 to 23 May 2015), Trove (2009 to 23 May 2015; previously Australasian Digital Theses Program (1997 to December 2008)) and Proquest Dissertations and Theses (2009 to 23 May 2015; previously Proquest Digital Dissertations (1980 to 23 May 2015)). We handsearched the reference lists of potentially relevant reports and two nursing journals. SELECTION CRITERIA: We included randomized and quasi-randomized trials examining effects of lateral positioning in critically ill adults. We included manual or automated turns but limited eligibility to studies that included duration of body position of 10 minutes or longer. We examined each lateral position versus at least one comparator (opposite lateral position and/or another body position) for single therapy effects, and the lateral positioning schedule (repeated lateral turning) versus other positioning schedules for repetitive therapy effects. DATA COLLECTION AND ANALYSIS: We pre-specified methods to be used for data collection, risk of bias assessment and analysis. Two independent review authors carried out each stage of selection and data extraction and settled differences in opinion by consensus, or by third party adjudication when disagreements remained unresolved. We planned analysis of pair-wise comparisons under composite time intervals with the aim of considering recommendations based on meta-analyses of studies with low risk of bias. MAIN RESULTS: We included 24 studies of critically ill adults. No study reported mortality as an outcome of interest. Two randomized controlled trials (RCTs) examined lateral positioning for pulmonary morbidity outcomes but provided insufficient information for meta-analysis. A total of 22 randomized trials examined effects of lateral positioning (four parallel-group and 18 cross-over designs) by measuring various continuous data outcomes commonly used to detect adverse cardiopulmonary events within critical care areas. However, parallel-group studies were not comparable, and cross-over studies provided limited data as the result of unit of analysis errors. Eight studies provided some data; most of these were single studies with small effects that were imprecise. We pooled partial pressure of arterial oxygen (PaO2) as a measure to detect hypoxaemia from two small studies of participants with unilateral lung disease (n = 19). The mean difference (MD) between lateral positions (bad lung down versus good lung down) was approximately 50 mmHg (MD -49.26 mmHg, 95% confidence interval (CI) -67.33 to -31.18; P value < 0.00001). Despite a lower mean PaO2 for bad lung down, hypoxaemia (mean PaO2 < 60 mmHg) was not consistently reported. Furthermore, pooled data had methodological shortcomings with unclear risk of bias. We had similar doubts regarding internal validity for other studies included in the review. AUTHORS' CONCLUSIONS: Review authors could provide no clinical practice recommendations based on the findings of included studies. Available research could not eliminate the uncertainty surrounding benefits and/or risks associated with lateral positioning of critically ill adult patients. Research gaps include the effectiveness of lateral positioning compared with semi recumbent positioning for mechanically ventilated patients, lateral positioning compared with prone positioning for acute respiratory distress syndrome (ARDS) and less frequent changes in body position. We recommend that future research be undertaken to address whether the routine practice of repositioning patients on their side benefits all, some or few critically ill patients.

Midwives' Experiences, Education, and Support Needs Regarding Basic Newborn Resuscitation in Jordan.

Newborns who are compromised at birth require rapid attention to stabilize their respiration attempts. Lack of knowledge regarding basic newborn resuscitation is a contributing factor to poor newborn health outcomes and increased mortality. The purpose of this study was to explore Jordanian midwives' experiences, education, and support needs to competently perform basic newborn resuscitation. Qualitative descriptive methodology was used to analyze a convenience sample of 20 midwives. A thematic approach was used to analyze the data. Participants discussed their experiences of basic newborn resuscitation including knowledge, skills, and barriers and suggested solutions to improve practice. Four themes were revealed: lack of knowledge and skills in newborn resuscitation, organizational constraints, inadequate teamwork, and educational needs. The midwives perceived that their ability to perform newborn resuscitation was hindered by lack of knowledge and skills in newborn resuscitation, organizational constraints (such as lack of equipment), and poor co-ordination and communication among team members.

Prevalence of Sleep-disordered Breathing in Obese Patients with Chronic Hypoxemia. A Cross-Sectional Study.

RATIONALE: Hypoxemia in obese patients is likely to be associated with a high prevalence of sleep-disordered breathing. Supplemental oxygen is commonly used to treat chronic hypoxemia but carries some risk in obese individuals due to unrecognized comorbid obstructive sleep apnea (OSA) and obesity hypoventilation syndrome (OHS). OBJECTIVES: The first step in the estimation of this risk is to determine the prevalence of OSA and OHS in obese individuals with chronic, awake hypoxemia. METHODS: A single-center retrospective cohort study was performed to assess the prevalence and severity of OSA and OHS among obese individuals with hypoxemia. One hundred eighty-four individuals underwent arterial blood gas testing and polysomnography. One hundred fifty-eight of these individuals also had spirometry. MEASUREMENTS AND MAIN RESULTS: The prevalence of OSA was 80%, and the prevalence of OHS was 51%. Chronic obstructive pulmonary disease (COPD) was confirmed by spirometry in 49% of the cohort, and OSA was found in 69% of those individuals. The severity of hypoxemia in this cohort was not statistically related to COPD, OSA, or OHS. CONCLUSIONS: OSA and OHS are highly prevalent in obese patients with chronic awake hypoxemia, and OSA frequently coexists with COPD. Evaluation of chronic, awake hypoxemia solely based on arterial blood gas measurements and pulmonary function testing is not sufficient to identify OSA and OHS. Further diagnostic sleep testing should be performed to identify those who could benefit from alternative therapies and to avoid potential harm from treatment with supplemental oxygen alone.

Conductive thermal ablation of 4T1 murine breast carcinoma reduces severe hypoxia in surviving tumour.

PURPOSE: The purpose of this study was to quantify hypoxia changes in viable tumour volumes after thermal ablation of a murine breast carcinoma. METHODS: Murine breast 4T1 tumours were grown in the rear leg of BALB/c mice to an average diameter of 10-12 mm. Tumours were treated with conductive interstitial thermal therapy (CITT) at a peak temperature of 80-90°C for 10 min. The animals were euthanised 72 h later, and the tumours were removed for immunohistochemical staining with pimonidazole - a marker of partial pressure of oxygen. The levels of pimonidazole staining intensity were used to quantify changes in hypoxia gradients in terms of strong, medium and weak positive pixel fractions. RESULTS: The pimonidazole staining ratio of viable control tumour tissue to viable tissue in tumours that were ablated was 0.7 for weak staining, 2.7 for medium staining and 8.0 (p < 0.03) for strong pimonidazole staining. CONCLUSION: This shift of pimonidazole staining toward lower intensity pixels in the remaining tumour indicates that tumour ablation with CITT may increase radiosensitivity of the remaining tumour tissue and presents a rationale for combination therapy.

Severe exercise-induced hypoxemia.

Exercise training is an essential component of pulmonary rehabilitation and is associated with improved function and other important outcomes in persons with chronic lung disease. A subset of pulmonary rehabilitation patients experience hypoxemia that may occur or worsen with exercise. For the purpose of this review, severe exercise-induced hypoxemia is defined as an S(pO(2)) of < 89% during exercise, despite use of supplemental oxygen delivered at up to 6 L/min. There is a paucity of evidence and clinical guidelines that address assessment and management of this important manifestation of chronic lung disease. This review presents background of this topic and suggests strategies for assessment, management, and safety measures for patients with severe exercise-induced hypoxemia.

Trans sodium crocetinate: functional neuroimaging studies in a hypoxic brain tumor.

OBJECT: Intratumoral hypoxia is believed to be exhibited in high-grade gliomas. Trans sodium crocetinate (TSC) has been shown to increase oxygen diffusion to hypoxic tissues. In this research, the authors use oxygen-sensitive PET studies to evaluate the extent of hypoxia in vivo in a glioblastoma model and the effect of TSC on the baseline oxygenation of the tumor. METHODS: The C6 glioma cells were stereotactically implanted in the right frontal region of rat brains. Formation of intracranial tumors was confirmed on MR imaging. Animals were injected with Copper(II) diacetyl-di(N4-methylthiosemicarbazone) (Cu-ATSM) and then either TSC or saline (6 rats each). Positron emission tomography imaging was performed, and relative uptake values were computed to determine oxygenation within the tumor and normal brain parenchyma. Additionally, TSC or saline was infused into the animals, and carbonic anhydrase 9 (CA9) and hypoxia-inducing factor-1α (HIF-1α) protein expression were measured 1 day afterward. RESULTS: On PET imaging, all glioblastoma tumors demonstrated a statistically significant decrease in uptake of Cu-ATSM compared with the contralateral cerebral hemisphere (p = 0.000002). The mean relative uptake value of the tumor was 3900 (range 2203-6836), and that of the contralateral brain tissue was 1017 (range 488-2304). The mean relative hypoxic tumor volume for the saline group and TSC group (6 rats each) was 1.01 ± 0.063 and 0.69 ± 0.062, respectively (mean ± SEM, p = 0.002). Infusion of TSC resulted in a 31% decrease in hypoxic volume. Immunoblot analysis revealed expression of HIF-1α and CA9 in all tumor specimens. CONCLUSIONS: Some glioblastomas exhibit hypoxia that is demonstrable on oxygen-specific PET imaging. It appears that TSC lessens intratumoral hypoxia on functional imaging. Further studies should explore relative hypoxia in glioblastoma and the potential therapeutic gains that can be achieved by lessening hypoxia during delivery of adjuvant treatment.

Operation Everest II.

In October 1985, 25 years ago, 8 subjects and 27 investigators met at the United States Army Research Institute for Environmental Medicine (USARIEM) altitude chambers in Natick, Massachusetts, to study human responses to a simulated 40-day ascent of Mt. Everest, termed Operation Everest II (OE II). Led by Charlie Houston, John Sutton, and Allen Cymerman, these investigators conducted a large number of investigations across several organ systems as the subjects were gradually decompressed over 40 days to the Everest summit equivalent. There the subjects reached a V(O)(2)max of 15.3 mL/kg/min (28% of initial sea-level values) at 100 W and arterial P(O(2)) and P(CO(2)) of approximately 28 and approximately 10 mm Hg, respectively. Cardiac function resisted hypoxia, but the lungs could not: ventilation-perfusion inequality and O(2) diffusion limitation reduced arterial oxygenation considerably. Pulmonary vascular resistance was increased, was not reversible after short-term hyperoxia, but was reduced during exercise. Skeletal muscle atrophy occurred, but muscle structure and function were otherwise remarkably unaffected. Neurological deficits (cognition and memory) persisted after return to sea level, more so in those with high hypoxic ventilatory responsiveness, with motor function essentially spared. Nine percent body weight loss (despite an unrestricted diet) was mainly (67%) from muscle and exceeded the 2% predicted from energy intake-expenditure balance. Some immunological and lipid metabolic changes occurred, of uncertain mechanism or significance. OE II was unique in the diversity and complexity of studies carried out on a single, courageous cohort of subjects. These studies could never have been carried out in the field, and thus complement studies such as the American Medical Research Expedition to Everest (AMREE) that, although more limited in scope, serve as benchmarks and reality checks for chamber studies like OE II.