Onset Of Hypoxemia Research Articles

Nosocomial SARS-CoV-2 transmission in a neonatal unit in Botswana: chronic overcrowding meets a novel pathogen

We describe a cluster of six SARS-CoV-2 infections occurring in a crowded neonatal unit in Botswana, including presumed transmission among mothers, postnatal mother-to-neonate transmission and three neonate-to-healthcare worker transmissions. The...

A Review of Acute Respiratory Distress Syndrome Management and Treatment.

Acute respiratory distress syndrome (ARDS) was first described in 1967, but its definition has evolved considerably since then. ARDS is defined as the onset of hypoxemia, tachypnea, and loss of lung compliance due to some stimulus. In the United States, the incidence of ARDS has been growing because it is being increasingly recognized. The incidence of ARDS has also gone up recently due to the COVID-19 pandemic. To date, there is no known one treatment for ARDS. Multiple studies have looked into various causes of ARDS, pathophysiology, and ventilation and management strategies. However, there is still considerable variability in the treatment and management of these patients from institution to institution. A literature search was conducted through PubMed and Google Scholar. Publications describing the epidemiology, diagnostic criteria, pathophysiology, and treatment were included in this review. The definition of ARDS has evolved over the years. The most recent and agreed upon diagnostic criteria are based on the Berlin criteria for ARDS. Management of patients with ARDS includes low tidal volume ventilation, prone ventilation, paralysis in certain patient populations, and perhaps extracorporeal membrane oxygenation (ECMO). This also applies to patients with ARDS due to COVID-19. Patients with ARDS have a high mortality due to the incredibly complex disease process. Because of the complexity of ARDS, the management and treatment is equally as difficult. This article reviews some of the strategies used to date, including the role of ECMO, and includes some society recommendations. Further research must be done into which methods best guide lung ventilation in severe ARDS and patients on ECMO.

Prognostic classification based on P/F and PEEP in invasively ventilated ICU patients with hypoxemia\u2014insights from the MARS study

BackgroundOutcome prediction in patients with acute respiratory distress syndrome (ARDS) greatly improves when patients are reclassified based on predefined arterial oxygen partial pressure to fractional inspired oxygen ratios (PaO2/FiO2) and positive end–expiratory pressure (PEEP) cutoffs 24 h after the initial ARDS diagnosis. The aim of this study was to test whether outcome prediction improves when patients are reclassified based on predefined PaO2/FiO2 and PEEP cutoffs 24 h after development of mild hypoxemia while not having ARDS.MethodsPost hoc analysis of a large prospective, multicenter, observational study that ran in the ICUs of two academic hospitals in the Netherlands between January 2011 and December 2013. Patients were classified into four groups using predefined cutoffs for PaO2/FiO2 (250 mmHg) and PEEP (5 cm H2O), both at onset of hypoxemia and after 24 h: PaO2/FiO2 ≥ 250 mmHg and PEEP < 6 cm H2O (group I), PaO2/FiO2 ≥ 250 mmHg and PEEP ≥ 6 cm H2O (group II), PaO2/FiO2 < 250 mmHg and PEEP < 6 cm H2O (group III), and PaO2/FiO2 < 250 mmHg and PEEP ≥ 6 cm H2O (group IV), to look for trend association with all-cause in-hospital mortality, the primary outcome. Secondary outcome were ICU- and 90-day mortality, and the number of ventilator-free days or ICU-free days and alive at day 28.ResultsThe analysis included 689 consecutive patients. All-cause in-hospital mortality was 35%. There was minimal variation in mortality between the four groups at onset of hypoxemia (33, 36, 38, and 34% in groups I to IV, respectively; P = 0.65). Reclassification after 24 h resulted in a strong trend with increasing mortality from group I to group IV (31, 31, 37, and 48% in groups I to IV, respectively; P < 0.01). Similar trends were found for the secondary endpoints.ConclusionsReclassification using PaO2/FiO2 and PEEP cutoffs after 24 h improved classification for outcome in invasively ventilated ICU patients with hypoxemia not explained by ARDS, compared to classification at onset of hypoxemia.Trial registrationClinicalTrials.gov identifier: NCT01905033. Registered on July 11, 2013. Retrospectively registered.

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Efficacy of Almitrine in the Treatment of Hypoxemia in Sars-Cov-2 Acute Respiratory Distress Syndrome

Emerging trends, techniques, and equipment for airway management in pediatric patients.

Pediatric patients present unique anatomic and physiologic considerations in airway management, which impose significant physiologic limits on safe apnea time before the onset of hypoxemia and subsequent bradycardia. These issues are even more pronounced for the pediatric difficult airway. In the last decade, the development of pediatric sized supraglottic airways specifically designed for intubation, as well as advances in imaging technology such that current pediatric airway equipment now finally rival those for the adult population, has significantly expanded the pediatric anesthesiologist's tool kit for pediatric airway management. Equally important, techniques are increasingly implemented that maintain oxygen delivery to the lungs, safely extending the time available for pediatric airway management. This review will focus on emerging trends and techniques using existing tools to safely handle the pediatric airway including videolaryngoscopy, combination techniques for intubation, techniques for maintaining oxygenation during intubation, airway management in patients at risk for aspiration, and considerations in cannot intubate cannot oxygenate scenarios.

Rapid Onset of Hypoxemia in a Man with Graft-versus-Host Disease after Stem Cell Transplant Leukemia

Rapid Onset of Hypoxemia in a Man with Graft-versus-Host Disease after Stem Cell Transplant Leukemia

A Practical Approach to Apneic Oxygenation during Endotracheal Intubation

Patients undergoing general anesthesia with endotracheal intubation are exposed to a brief apnea period that is usually well tolerated. Conventional preoxygenation techniques may not provide adequate time for safe airway management in patients at high risk for desaturation or when an unanticipated difficult airway arises. Continuous oxygen administration during the apnea period, termed apneic oxygenation, can be used in conjunction with traditional pre-oxygenation techniques to prolong the time to patient desaturation when tracheal intubation is attempted. Clinical studies have evaluated the efficacy of apneic oxygenation using multiple techniques, nasopharyngeal catheters, nasal prongs, modified laryngoscopes, and buccal oxygen administration, all proved to be effective at prolonging the duration of apnea, by delaying the onset of hypoxemia.

A reply

Thank you for the opportunity to reply to Drs Dhara and Liu. We are delighted that our paper has generated some interest. Our primary purpose in performing this study was to ascertain the safety of transtracheal jet ventilation (TTJV) via a Ravussin catheter, which we advocate for elective use and for airway rescue. As such our observations and comments are principally concerned with this and not ‘high frequency oscillatory jet ventilation’ and transglottic techniques. We still question the usefulness of measuring upper tracheal pressure at one fixed point (from a proximal lumen) above the jet exit (from the distal lumen) when we have clearly shown quite different pressure profiles along the length of the trachea, with the highest pressure measured distally at the carina. We believe that for quantifying airway pressures it is necessary to make measurements at least as far as the carina. The transduced fibrescope is a simple system for performing this task. We agree that jetting directly onto the tracheal mucosa may be problematic and would counsel against using non-dedicated equipment. The anterior curve and stiffness of the Ravussin catheter together with the side holes at the distal end tend to centre the jet stream in the trachea, thus making it the catheter of choice for transtracheal jet ventilation [1, 2]. This is not the case with a much softer multilumen intravenous catheter. In Dhara and Butler's case report [3], the rigidity of the multilumen catheter was attributed to the foil wrapped around the catheter and not the stiffness of the catheter used. Clearly structures proximal to the glottis can cause expiratory obstruction and we therefore stressed the importance of maintaining a clear expiratory pathway during TTJV. At endoscopy in these patients there was no pathological airway obstruction and given the small diameter and flexibility of the fibrescope it is unlikely to have significantly contributed to maintaining a patent airway or altering the measured pressures. Layman's original report is in keeping with our findings of no significant negative pressure phase [4]. As an additional point, we were dismayed to see the Difficult Airway Society in the UK not making a clear and unambiguous statement in favour of small needle transtracheal ventilation as first choice technique for the ‘can’t ventilate, can't intubate' scenario in its guidelines [5], and furthermore inserting a warning therein effectively promoting recourse to such techniques only after the onset of hypoxaemia. We would maintain that no patient should suffer an airway death without a timely and competent attempt at transtracheal ventilation having been made using dedicated equipment [6].

Nitric Oxide Synthesis Inhibition during Cerebral Hypoxemia and Reoxygenation with 100% Oxygen in Newborn Pigs

The objective of our study was to evaluate the effects of N_σ-nitro-L-arginine methyl ester (L-NAME), an inhibitor of the nitric oxide (NO) pathway, on cerebral microcirculation during hypoxemia and reoxygenation with 100% oxygen in newborn pigs. Twenty-two pigs were randomized to hypoxemia [inspired fraction of oxygen (FIO₂) 0.08; 20 min] and reoxygenation (FIO₂ 1.0; 60 min) or normoxia. The hypoxemic animals were further randomized to receive either an intravenous bolus injection of 5 mg/kg L-NAME (n = 8) or a corresponding volume of isotonic saline (n = 8) 30 min before the onset of hypoxemia. The normoxemic group (n = 6) received the same pretreatment with L-NAME. Cerebral hemodynamics were assessed by laser Doppler flowmetry and intracranial pressure monitoring. The cerebral NO concentration was continuously measured using an electrochemical sensor. Pretreatment with L-NAME resulted in a more severe systemic hypotension and reduced cerebral microcirculation during the period of hypoxemia compared with the saline/hypoxemia group. NO synthesis inhibition during reoxygenation with 100% oxygen, however, blunted the increase in NO concentration (p < 0.05) without reduction of cerebral blood flow and cerebral perfusion pressure. In conclusion, in this newborn pig model, pretreatment with a bolus infusion of L-NAME induced severe hypotension and reduced cerebral microcirculation during hypoxemia. However, it appears to have no significant adverse effect on cerebral hemodynamics during the period of reoxygenation with 100% oxygen. This deleterious effect during hypoxemia limits the use of L-NAME as a preventive drug but suggests beneficial effects during reoxygenation with 100% oxygen.

An in vivo nitric oxide clamp to investigate the influence of nitric oxide on continuous umbilical blood flow during acute hypoxaemia in the sheep fetus.

1. The aims of this study in the ovine fetus were to (1) characterise continuous changes in umbilical blood flow and vascular conductance during acute hypoxaemia and (2) determine the effects of nitric oxide blockade on umbilical blood flow and vascular conductance during normoxic and hypoxaemic conditions using a novel in vivo 'nitric oxide clamp'. 2. Under 1-2% halothane anaesthesia, seven ovine fetuses were instrumented between 118 and 125 days of gestation (term is ca 145 days) with vascular and amniotic catheters and a flow probe around an umbilical artery. At least 5 days after surgery, all fetuses were subjected to a 3 h protocol: 1 h of normoxia, 1 h of hypoxaemia and 1 h of recovery during fetal I.V. infusion with saline or, 1-2 days later, during combined fetal treatment with the nitric oxide (NO) inhibitor N (G)-nitro-L-arginine methyl ester (L-NAME, 100 mg x kg(-1)) and the NO donor sodium nitroprusside (NP, 5.1 +/- 2.0 microg x kg(-1) x min(-1), the 'nitric oxide clamp'). Following the end of the 3 h experimental protocol, the infusion of NP was withdrawn to unmask any persisting effects of fetal treatment with L-NAME alone. 3. During acute hypoxaemia, the reduction in arterial partial pressure of O2 (Pa,O2) was similar in fetuses infused with saline or treated with the nitric oxide clamp. In all fetuses, acute hypoxaemia led to a progressive increase in mean arterial blood pressure and a fall in heart rate. In saline-infused fetuses, acute hypoxaemia led to a rapid, but transient, decrement in umbilical vascular conductance. Thereafter, umbilical vascular conductance was maintained and a significant increase in umbilical blood flow occurred, which remained elevated until the end of the hypoxaemic challenge. In contrast, while the initial decrement in umbilical vascular conductance was prevented in fetuses treated with the nitric oxide clamp, the increase in umbilical blood flow during hypoxaemia was similar to that in fetuses infused with saline. After the 1 h recovery period of the acute hypoxaemia protocol, withdrawal of the sodium nitroprusside infusion from fetuses undergoing the nitric oxide clamp led to a significant, but transient, hypertension and a sustained umbilical vasoconstriction. 4. In conclusion, the data reported in this study of unanaesthetised fetal sheep (1) show that minute-by-minute analyses of haemodynamic changes in the umbilical vascular bed reveal an initial decrease in umbilical vascular conductance at the onset of hypoxaemia followed by a sustained increase in umbilical blood flow for the duration of the hypoxaemic challenge, (2) confirm that the increase in umbilical blood flow after 15 min hypoxaemia is predominantly pressure driven, and (3) demonstrate that nitric oxide plays a major role in the maintenance of umbilical blood flow under basal, but not under acute hypoxaemic, conditions.

Mechanical ventilation with a lower tidal volume resulted in decreased mortality in patients with acute lung injury and the acute respiratory distress syndrome

The Acute Respiratory Distress Syndrome Network. Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome. N Engl J...

Chemoreflex and endocrine components of cardiovascular responses to acute hypoxemia in the llama fetus.

We tested the hypothesis that the llama fetus has a blunted cardiovascular chemoreflex response to hypoxemia by investigating the effects of acute hypoxemia on perfusion pressure, heart rate, and the distribution of the combined ventricular output in 10 chronically instrumented fetal llamas at 0.6-0.7 gestation. Four llama fetuses had the carotid sinus nerves sectioned. In the intact fetuses, there was a marked bradycardia, an increase in perfusion pressure, and a pronounced peripheral vasoconstriction during hypoxemia. These cardiovascular responses during hypoxemia in intact fetuses were accompanied by a pronounced increase in plasma vasopressin, but not in plasma angiotensin II concentrations. Carotid denervation prevented the bradycardia at the onset of hypoxemia, but it did not affect the intense vasoconstriction during hypoxemia. Plasma vasopressin and angiotensin II levels were not measured in carotid-denervated fetuses. Our results do not support the hypothesis that the carotid chemoreflex during hypoxemia is blunted in the llama fetus. However, they emphasize that other mechanisms, such as increased vasopressin concentrations, operate to produce an intense vasoconstriction in hypoxemia. This intense vasoconstriction in the llama fetus during hypoxemia may reflect the influence of chronic exposure to the hypoxia of high altitude on the magnitude and gain of fetal cardiovascular responses to a superimposed acute episode of hypoxemia.

Cardiac function in fetal sheep during two weeks of hypoxemia.

Although several studies have examined fetal cardiac responses to acute hypoxemia, relatively little is known of the response to prolonged hypoxemia. To determine the effects of long-term hypoxemia on ovine fetal cardiac function, we measured right (QRV) and left ventricular outputs (QLV) and determined the effects of increasing preload (ventricular function curve) and afterload (arterial pressure sensitivity curve) on the left ventricle. Six days after fetal surgical instrumentation with catheters and electromagnetic flow probes (approximately 123 days gestation), we administered N2 into the maternal trachea for 14 days to reduce maternal PO2 to approximately 55 Torr (hypoxemic group, Hyp, n = 6). Normoxic animals were used as controls (Cont, n = 6). With the onset of hypoxemia, fetal arterial PO2 was reduced from approximately 27 to approximately 18 Torr. Fetal heart rate in Hyp fetuses decreased approximately 22% on day 14 compared with Cont (P < 0.05). Mean arterial pressure in the Hyp group was higher than that of Cont but not significantly so. Right and left atrial pressures were not affected by hypoxemia. QRV in Hyp fetuses was maintained on day 1 but decreased significantly by day 3 (approximately 19%) and further decreased on days 7 (approximately 28%) and 14 (approximately 34%). QLV was not depressed until day 7 (approximately 20%), with a further decrease on day 14 (approximately 38%). In association with the decreased QLV the plateau of the ventricular function curve in Hyp fetuses was depressed significantly on days 7 and 14. In contrast, the slope of the arterial pressure sensitivity curve in the Hyp group did not differ from Cont.(ABSTRACT TRUNCATED AT 250 WORDS)

Fetal iron and cytochrome c status after intrauterine hypoxemia and erythropoietin administration.

Chronic fetal hypoxemia stimulates erythropoiesis and may result in a redistribution of fetal iron from plasma into erythrocytes. We studied the response of fetal plasma erythropoietin (Ep) to hypoxemia, the role of Ep in stimulating erythropoiesis in utero, and the effect of augmented erythropoiesis on fetal plasma Ep and iron and tissue cytochrome c concentrations in 19 chronically instrumented late-gestation fetal sheep. The fetuses were stimulated to produce 28 erythropoietic responses after exposure to 1) acute hypoxemia (1-5 days), 2) chronic hypoxemia (greater than 7 days), and/or 3) administration of 1,500 U recombinant human Ep concurrently during normoxemia. Plasma Ep peaked less than 12 h after the onset of hypoxemia or Ep bolus. Plasma iron decreased 24-48 h later and returned to baseline 48-96 h after normalization of Ep levels to baseline. The plasma iron response was directly related to the erythropoietin stimulus (r = 0.79, P less than 0.001) and inversely related to liver iron concentration at death (r = -0.84, P less than 0.001). Nine fetuses with depleted liver iron concentrations at autopsy had significantly lower heart and skeletal muscle iron concentrations compared with animals with 10% of control liver iron remaining. Skeletal muscle and heart iron and cytochrome c concentrations were significantly correlated. Ep has a potent biological effect on fetal erythropoiesis and iron metabolism. Augmented fetal erythropoiesis, mediated by Ep, results in decreased plasma iron, hepatic storage iron, and skeletal and cardiac muscle iron and cytochrome c. The model potentially explains the iron abnormalities found in newborn infants after fetal hypoxia.

Effects of hypoxemia with and without acidemia on the isometric contraction time and the electromechanical delay of the fetal myocardium: An experimental study on the ovine fetus

This study assessed the response of the preejection period during hypoxemia with and without acidemia. In five pregnant ewes, hypoxemia was created during 1 hour followed by fetal infusion of lactic acid during 2 hours. A micromanometer catheter positioned above the fetal aortic valve, an endocavitary phonocardiogram, and a fetal electrocardiogram allowed measurements of the two components of the preejection period--the isometric contraction time and the electromechanical delay. At the onset of hypoxemia, because of changes in isometric contraction time, the preejection period began to shorten. When acidemia was induced, the preejection period modified slowly in the opposite direction and lengthened, initially because of a prolongation of electromechanical delay and later because of an increase in the already shortened isometric contraction time. This process developed slowly and at the end of 2 hours of acidemia, preejection period were back to preexperimental values. It can be concluded that systolic time intervals can be normal and misleading when acidosis complicates hypoxemia.

Effects of fructose-1,6-diphosphate, glucose, and saline on cardiac resuscitation.

Severe hypoxemia causes respiratory and cardiac arrest, in part, because severe hypoxemia decreases glycolysis and adenosine triphosphate (ATP) production by a lactic acid-induced decrease in the activity of phosphofructokinase and glyceraldehyde-3-P dehydrogenase. Fructose-1,6-diphosphate (FDP) administration increases the ATP concentration of blood. The authors hypothesized that FDP might increase the number of rabbits that could be resuscitated from hypoxemic cardiac arrest. To test this hypothesis, heart rate, arterial pressure, left ventricular end-diastolic pressure, and blood gases and pH were measured during normoxemia (FIO2 = 0.21) and again during hypoxemia (FIO2 = 0.04) in 28 adult, white, New Zealand rabbits anesthetized with pentobarbital. With the onset of hypoxemia, we gave either 40 mg/kg of 5% FDP (n = 10), 5% glucose (n = 11), or an equal volume (2.5 ml) of normal saline (n = 7) intravenously and began a continuous infusion of 2.0 mg X kg-1 X min-1 of the same sugar or 0.12 ml/min of saline. FDP-treated rabbits breathed for 20.9 +/- 4.9 (mean +/- SEM) min after initiation of hypoxemia; glucose-treated rabbits breathed for 1.4 +/- 0.2 min, and saline-treated rabbits breathed 10.3 +/- 4 min. Cardiac arrest occurred 2.5 +/- 0.5 min after the onset of respiratory arrest in FDP-treated rabbits, 4.1 +/- 0.2 min in glucose-treated rabbits, and 2.9 +/- 0.4 min in saline-treated rabbits. We could resuscitate all ten FDP-treated rabbits; two of 11 glucose-treated (FDP vs. glucose, P less than 0.001); and one of seven saline-treated rabbits (FDP vs. saline, P less than 0.001) from cardiac arrest.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic hypoxemia in the newborn lamb: cardiovascular, hematopoietic, and growth adaptations.

We have created a model of chronic hypoxemia in the newborn lamb by decreasing pulmonary blood flow in the presence of an atrial septal defect. Via a left lateral thoracotomy, we place an inflatable balloon around the pulmonary artery and perform an atrial septostomy under direct vision. We also insert several vascular catheters and place an electromagnetic flow transducer around the ascending aorta. Three days after surgery, we inflated the balloon in 11 lambs such that arterial oxygen saturation decreased to 60 to 75%. Studies were performed on these lambs twice weekly and weekly on 12 normoxemic lambs. Growth decreased sharply (47 +/- 123 versus 221 +/- 82 g/day) at the onset of hypoxemia and remained low, although oxygen consumption followed the normal gradual decline. Heart rate remained elevated throughout the study. Arterial PCO2 levels decreased from 40 +/- 5 to 35 +/- 7 torr and remained low. Systemic blood flow decreased at balloon inflation but quickly returned to normal. Mixed venous saturation was low, but could decrease further with shivering. Systemic oxygen delivery decreased initially but returned to normal as Hb concentration rose (from 9.4 +/- 1.5 to 12.5 +/- 2.2 g/dl). P50 increased normally over the study period. Four of the 11 hypoxemic lambs died during the study. These data show that, in the chronically hypoxemic newborn, systemic oxygen delivery is maintained primarily by a rising Hb. Total body oxygen consumption is maintained at rest but is redistributed away from anabolic requirements and toward cardiorespiratory work. This signal to decrease growth occurs despite less than maximal oxygen extraction at rest.

319 CHRONIC HYPOXEMIA IN THE NEWBORN LAMB

The adaptive mechanisms by which oxygen delivery is maintained during chronic hypoxemia, and the costs of such adaptations, are not well defined. In the newborn lamb, we have induced chronic hypoxemia by placing an inflatable balloon around the pulmonary artery after performing an atrial septostomy. Three days after surgery, the balloon was gradually inflated in 11 lambs to create a right-to-left atrial shunt such that arterial oxygen saturation was between 60 and 75%. Twice weekly studies were performed on these lambs and weekly studies on 12 normoxemic lambs. Growth decreased sharply (47 ± 123 vs 221 ± 82 g/day) at the onset of hypoxemia and remained low, although oxygen consumption followed the normal gradual decline. Systemic blood flow decreased at balloon inflation but quickly returned to normal. Mixed venous and coronary sinus saturations were low, but could decrease further with shivering. Systemic oxygen delivery returned to normal as hemoglobin concentration rose (from 9.4 ± 1.5 to 12.5 ± 2.2 g/dl). P50 did not change. Four of the 11 hypoxemic lambs died during the 2 week study period. These data show that systemic oxygen delivery is maintained primarily by rising hemoglobin in the chronically hypoxemic newborn. There is a signal to decrease growth apparently to maintain some reserve. The limited reserve is shown by a high mortality rate despite normal oxygen delivery at rest.

Suctioning and Cerebral Blood Flow

To the Editor.— The article by Perlman and Volpe1 provides interesting information on physiologic changes associated with suctioning in the preterm infant. My observations during laryngoscopy and endotracheal intubation in preterm infants have also revealed a significant increase in arterial blood pressure which occurred before the onset of hypoxemia. It is possible that mechanical stimulation of the laryngopharyngeal and tracheobronchial regions as described in cats2 may arouse reflexes that increase sympathetic efferent activity, thereby contributing to the increase in blood pressure.

An Arterial Blood Gas Diagram for Clinical Use

A simple diagram for arterial blood gas tensions was constructed from values obtained from normal volunteers at rest, during voluntary breath-holding and during maximal voluntary hyperventilation. Thus, an appropriate arterial oxygen tension (PaO2) was established for any physiologic level of alveolar ventilation, as reflected by the arterial carbon dioxide tension (PaCO2). Blood gas tensions of 177 ambulatory patients with differing clinical types of pulmonary insufficiency were plotted against the diagram and the magnitude of the observed deviations from the normal range were compared to selected pulmonary function test results. The vast majority of test results exhibited lower oxygen tensions than predicted from the observed PaCO2. This actual-predicted PaO2 difference was directly related to the severity of airways obstruction in chronic obstructive pulmonary disease and to the severity of restriction in interstitial lung diseases. Patients in the early stages of lung disease had resting hypocarbia before the onset of hypoxemia or of significant pulmonary function test abnormality. The diagram provides a simple, rapid clinical method of diagnosing and estimating the severity of the blood gas disturbances which reflect V ˙ / Q ˙ mismatching at any physiologic level of alveolar ventilation.