Significant Arterial Hypoxemia Research Articles

Clinical Phenotypes of Hypoxia in Patients with COVID-19

The aim of the studywas to examine the clinical phenotypes of hypoxia in patients with COVID-19 in relation to the severity of acute respiratory failure (ARF).Material and methods. Sixty patients with severe COVID-19 and manifestations of acute respiratory failure admitted to the infectious disease hospitals of Nizhny Novgorod were enrolled in the study.The study included patients with transcutaneous saturation (SpO2) below 93% on spontaneous breathing, who required correction of respiratory alterations according to the Interim Clinical Guidelines for the Treatment of Patients with COVID-19. All patients were divided into 2 groups of 30 patients each according to the nature of respiratory impairment. Group 1 included patients without breathing difficulties who had respiratory rate up to 25 per minute. Group 2 patients had breathing difficulties and respiratory rate over 25 per minute.In addition to SpO2, severity of respiratory difficulties, respiratory rate (RR), forced breathing (FB), heart rate (HR), acid-base balance (ABB) and arterial and venous blood gases, capillary refill time, blood lactate level were assessed. The severity of lung involvement was determined using chest computed tomography, and severity of disease was assessed using the NEWS score. Respiratory treatment required for ARF correction and the outcome of hospitalization were also considered.Results. In group 1, the mean age was 66 (56; 67) years and the disease severity was 8 (7; 10) points. Group 1 patients had minor tachycardia and tachypnoea, there were no lactate elevation or prolonged capillary refill time. Mean SpO2was as low as 86 (83; 89)%. Venous blood pH and pCO2 values were within normal reference intervals, mean BE was 6 (4; 9) mmol/l, pO2was 42 (41; 44) mm Hg, and SO2was 67 (65; 70)%. Mean arterial blood pO2was 73 (69; 75) mm Hg, SO2was 86 (83; 90)%, and O2was 37 (35; 39) mm Hg. Oxygen therapy with the flow rate of 5-15 l/min in prone position helped correct ARF. All patients of this group were discharged from hospital.In group 2, the mean age was 76 (70;79) years and the disease severity was 14 (12; 18) points. Anxiety was observed in 15 patients, prolonged capillary refill time was seen in 13 patients, and increased lactate level in 18 patients. Mean RR was 34 (30; 37) per minute, HR was 110 (103; 121) per minute, and SpO2was 76 (69; 83)%. Mean venous blood pH was 7.21 (7.18; 7.27), pCO2was 69 (61; 77) mm Hg, BE was -5 (-7; 2) mmol/l, pO2was 25 (22; 28) mm Hg, SO2was 47 (43; 55)%. Mean arterial blood pO2was 57 (50; 65) mm Hg, SO2was 74 (69; 80)%, and pCO2was 67 (58; 74) mm Hg. In the group 2 patients, the standard oxygen therapy in prone position failed to correct ARF, and high flow oxygen therapy, noninvasive CPAP with FiO2of 50-90% or noninvasive CPAP+PS were administered. Fourteen patients were started on invasive lung ventilation. There were 10 fatal outcomes (33%) in this group.Conclusion. Two clinical phenotypes of hypoxia in patients with COVID-19 can be distinguished. The first pattern is characterized by reduced SpO2(80-93%), no tachypnoea (RR >25 per minute) and moderate arterial hypoxemia without tissue hypoxia and acidosis («silent hypoxia»). It is typical for younger patients and associates with less lung damage and disease severity than in patients with severe ARF. Hypoxemia can be corrected by prone position and oxygen therapy and does not require switching to mechanical ventilation. The second pattern of hypoxia is characterized by significant arterial hypoxemia and hypercapnia with tissue hypoxia and acidosis. Its correction requires the use of noninvasive or invasive mechanical ventilation.

The Frequency and Significance of Portopulmonary Venous Anastomosis (PPVA) and Transvenous Obliteration for Gastric Varices

A Portopulmonary Venous Anastomosis (PPVA) is a direct vascular connection between the portal venous system and the pulmonary veins, close to the left atrium. We describe a patient with advanced cirrhosis and moderately severe Hepatopulmonary Syndrome (HPS) in whom (PPVA) was demonstrated by a high resolution computed tomographic scan. In order to reduce the symptoms of hypoxia in our patient, we sequentially performed Transjugular Intrahepatic Portosystemic Shunt (TIPS) followed by a catheter based obliteration of the PPVA. The case raised three questions which were addressed through an extensive literature review. Among patients with advanced cirrhosis, what is the frequency of PPVA? Our literature review suggests that the frequency of finding a PPVA in patients with portal hypertension depends on the imaging technique used. Transhepatic or transvenous portal venography may demonstrate PPVA in about 20% of patients with cirrhosis and varices. Limited published experience with contrast enhanced (bubble) echocardiography suggests that PPVA may be present in about 30% of such patients. An increasing number of case reports of PPVA have been published in recent years. This observation indicates that routine use of High Resolution Computed Tomography (HRCT) and magnetic resonance imaging is able to identify PPVA in cirrhotic patients. The visualization of PPVA with HRCT depends on the timing of the contrast injection and the expertise of the viewer. The present report describes three patients with portopulmonary venous anastomosis (PPVA) in whom balloon-occluded retrograde transvenous obliteration (B-RTO) of gastric varices was attempted. No patients had a gastrorenal shunt. In one patient, after an approach from the inferior phrenic vein (IPV), the PPVA was embolized with the use of microcoils. Portopulmonary Venous Anastomosis Detected at Balloon-occluded Retrograde Transvenous Obliteration for Gastric Varices among cirrhotic patients with PPVA, what is the clinical significance of the PPVA? There are multiple causes of clinically significant hypoxia in patients with cirrhosis. A PPVA is a right to left shunt that, theoretically, could be associated with clinically significant systemic arterial hypoxemia or emboli. There is not definitive evidence in the published literature that PPVA alone causes clinically significant hypoxia in cirrhotic patients. PPVA is, however, a documented important risk factor for systemic emboli when needle or catheter techniques are used to treat or prevent bleeding from gastroesophageal varices.

Ischemic Preconditioning Does Not Improve Peak Exercise Capacity at Sea Level or Simulated High Altitude

Ischemic preconditioning (IPC) may improve blood flow and oxygen delivery to tissues, including skeletal muscle, and has the potential to improve intense aerobic exercise performance, especially that which results in arterial hypoxemia. PURPOSE: To determine the effects of IPC of the legs on peak exercise capacity (Wpeak), submaximal and peak cardiovascular hemodynamics, and peripheral capillary oxygen saturation (SpO2) in trained males at sea level (SL) and simulated high altitude (HA; 13.3% FIO2, ∼3650 m). METHODS: Fifteen highly trained male cyclists and triathletes completed two Wpeak tests (SL and HA) and four experimental exercise trials (10 min at 55% altitude specific Wpeak then increasing by 30 W every 2 min until exhaustion) with and without IPC. RESULTS: HA resulted in significant arterial hypoxemia during exercise compared to SL (73 ± 6 vs. 93 ± 4% SpO2, p < 0.001) that was associated with 21% lower Wpeak values. IPC did not significantly improve Wpeak at SL or HA. Additionally, IPC failed to improve cardiovascular hemodynamics or SpO2 during submaximal exercise or at Wpeak. CONCLUSION: IPC performed 45 min prior to exercise does not improve Wpeak or systemic oxygen delivery during submaximal or peak exercise at SL or HA. Future studies must examine the influence of IPC on local factors such as working limb blood flow, oxygen delivery, and arteriovenous oxygen difference as well as whether the effectiveness of IPC is altered by the volume of muscle made ischemic, the timing prior to exercise, and high altitude acclimatization.

Alveolar to Arterial Gas Exchange During Constant-load Exercise in Healthy Active Men and Women

Exercise-induced arterial hypoxemia (EIAH) can result from inadequate hyperventilation and/or inefficient alveolar to arterial gas exchange. For these circumstances to occur demand typically exceeds capacity; as such, EIAH is more often reported in highly trained individuals (∼50%) during progressive maximal exercise. However, it has also been observed during lower levels of exercise in some individuals and is suggested to have a higher incidence in trained women. PURPOSE: To determine if the alveolar to arterial O2 difference (AaDO2) and ventilatory response during constant-load exercise in healthy active, but not highly trained, individuals suggests an innate sex difference that would make females more susceptible to EIAH. METHODS: Thirty-one healthy, active male (M) and 33 female (F) subjects (VO2MAX: 39±7 vs. 31±6mL/min/Kg, M vs. F) completed 18min of exercise on a cycle ergometer (40 and 75% peak W 9min/stage) with the final stage progressing towards maximal by end exercise (VO2: 90±7 vs. 92±9%VO2MAX, M vs. F). At rest and every 3min during exercise arterial blood gases were drawn and cardiac output (Q) was measured, while gas exchange was continuously assessed. Partial pressure of alveolar O2 (PAO2), AaDO2 and change from baseline for PaO2, PaCO2 and SaO2 were calculated. RESULTS: Both males and females demonstrated AaDO2 widening with each 3min increment of exercise (M: 8.6±4.4, 9.2±5.2, 10.3±5.6, 14.9±5.6, 16.5±6.6, 16.3±6.2 vs. F: 7.5±3.7, 8.3±5.0, 9.5±4.1, 14.4±6.9, 16.4±7.1, 19.1±6.0; for minutes 3, 6, 9 at 40% and 12, 15, 18 at 75%). There was no evidence of a difference in ventilatory response or a relative hypoventilation between sexes. No significant arterial hypoxemia was noted, but 6 M (19%) and 5 F (15%) had a drop in SaO2 ≥2% by the final minute of exercise. There was a negative relationship between ΔSaO2 and Q, AaDO2, and ΔPaCO2 during 75%VO2MAX exercise (Q: r= -0.31 p=0.01; AaDO2: r= -0.28 p=0.03; ΔPaCO2: r= -0.43 p=0.00). CONCLUSIONS: There was no evidence of pulmonary gas exchange inefficiencies during exercise that would increase EIAH susceptibility in females. The reported higher incidence of EIAH in highly trained females compared males, therefore appears to be a result of training induced changes rather than innate sex specific inefficiencies. Funding support: NIH HL71478 and AHA 56051Z

The Frequency and Significance of Portopulmonary Venous Anastomosis (PPVA): A Case Report and Literature Review

A Portopulmonary Venous Anastomosis (PPVA) is a direct vascular connection between the portal venous system and the pulmonary veins, close to the left atrium. We describe a patient with advanced cirrhosis and moderately severe Hepatopulmonary Syndrome (HPS) in whom (PPVA) was demonstrated by a high resolution computed tomographic scan. In order to reduce the symptoms of hypoxia in our patient, we sequentially performed Transjugular Intrahepatic Portosystemic Shunt (TIPS) followed by a catheter based obliteration of the PPVA. The case raised three questions which were addressed through an extensive literature review. Among patients with advanced cirrhosis, what is the frequency of PPVA? Our literature review suggests that the frequency of finding a PPVA in patients with portal hypertension depends on the imaging technique used. Transhepatic or transvenous portal venography may demonstrate PPVA in about 20% of patients with cirrhosis and varices. Limited published experience with contrast enhanced (bubble) echocardiography suggests that PPVA may be present in about 30% of such patients. An increasing number of case reports of PPVA have been published in recent years. This observation indicates that routine use of High Resolution Computed Tomography (HRCT) and magnetic resonance imaging is able to identify PPVA in cirrhotic patients. The visualization of PPVA with HRCT depends on the timing of the contrast injection and the expertise of the viewer. Among cirrhotic patients with PPVA, what is the clinical significance of the PPVA? There are multiple causes of clinically significant hypoxia in patients with cirrhosis. A PPVA is a right to left shunt that, theoretically, could be associated with clinically significant systemic arterial hypoxemia or emboli. There is not definitive evidence in the published literature that PPVA alone causes clinically significant hypoxia in cirrhotic patients. PPVA is, however, a documented important risk factor for systemic emboli when needle or catheter techniques are used to treat or prevent bleeding from gastroesophageal varices. What is the evidence that the obliteration of a documented PPVA will improve oxygenation in a cirrhotic patient with hypoxemia? Modern imaging methods may demonstrate a PPVA when patients with cirrhosis are investigated because of hypoxia. Previous authors have argued that the right to left shunting of blood in a PPVA does not have enough flow to significantly lower arterial oxygen concentration. Our report documents that the obliteration of a PPVA can be accomplished. However, our patient's oxygenation did not improve with obliteration of the PPVA. We do not believe that PPVA causes hypoxia. But knowledge of the frequency and clinical significance of PPVA is important for the care of patients with cirrhosis.

Hypoxic challenge assessment in individuals with obstructive sleep apnea

Background The degree of arterial hypoxemia during air travel in individuals with obstructive sleep apnea (OSA) is not known. The Aerospace Medical Association considers a ground level arterial oxygen tension (PaO 2) above 9.3 kPa as safe before air travel. Methods Fifteen subjects with untreated OSA (mean apnea–hypopnea index [AHI] 43/h) and 14 with treated OSA (mean AHI on CPAP 1.9/h) completed an assessment including hypoxic challenge test (HCT). The groups had similar mean age, mean BMI and pre-treatment OSA severity. Results Four subjects, all in the untreated group and with resting PaO 2 >9.3 kPa and oxygen saturation (SpO 2) >95%, had a positive HCT (PaO 2 <6.6 kPa and/or SpO 2 <85%). The PaO 2 at the end of the HCT was significantly correlated with the minimum overnight SpO 2 ( r = .754, p = .002) but not with the daytime PaO 2 and SpO 2. Using a cut off value of 65%, the minimum overnight SpO 2 had positive and negative predictive values of 57% and 100% respectively. Conclusions OSA can be an additional risk factor for developing significant arterial hypoxemia during HCT. Baseline PaO 2 and SpO 2 did not predict arterial hypoxemia during the HCT. Minimum overnight SpO 2 <65% may be used as a cut off to advise further assessment. Effective treatment of OSA seems to be the best option before air travel.

99mTechnetium-macroaggregated albumin perfusion lung scan versus contrast enhanced echocardiography in the diagnosis of the hepatopulmonary syndrome in children with chronic liver disease

The hepatopulmonary syndrome (HPS) is a triad of advanced chronic liver disease (CLD), arterial hypoxemia and intrapulmonary arteriovenous shunting in the absence of a primary cardiopulmonary disease. HPS has been more frequently reported in adults than in children with no data on its prevalence in children with CLD. The aim of this study was to detect the prevalence of the HPS in a cohort of children with CLD because of chronic hepatitis B and/or C virus infection, schistosomiasis as well as inborn metabolic errors. We also aimed to evaluate the role of Technetium labeled macroaggregated albumin (Tc--MAA) perfusion lung scan versus contrast enhanced echocardiography (CEE) with intravenous injection of agitated saline in the diagnosis and quantification of intrapulmonary shunts and their relationship to important clinical and laboratory findings. Forty Egyptian children (22 males) were investigated. Their ages ranged from 5 to 12 years (with a mean of 9.5 years). Twenty individuals proved to have cirrhosis. Blood gas determination revealed more significant arterial hypoxemia in cirrhotics than noncirrhotics both under room air and after breathing 100% oxygen for 15 mins. CEE showed comparable cardiac measurements in cirrhotic and noncirrhotic patients, and diagnosed intrapulmonary shunts in three hypoxemic cirrhotic patients; whereas Tc--MAAperfusion lung scan diagnosed shunts in seven patients (five of them cirrhotic). The presence of shunts was significantly correlated with the duration of CLD, clinical findings, presence of cirrhosis and porto-systemic collaterals. We calculated for each patient a shunt index (SI) by the formula: (activity outside thorax/activity outside plus inside thorax) 100; and an SI value of 0.278 was found to be a cutoff value for shunt detection. All patients with SI above this value had shunting associated with hypoxemia and all patients with SI below this value had no hypoxemia (specificity 100%). Arterial hypoxemia and intrapulmonary shunts were diagnosed in 17.5% of this cohort of children with cirrhotic or noncirrhotic CLD representing the classic HPS. Tc--MAA perfusion lung scan was more sensitive than CEE in detection of intrapulmonary shunts. SI cutoff value of 0.278 was found to be highly specific for shunt detection and we recommend its validation in further studies.

Acute hypervolemia does not improve arterial oxygenation in maximally exercising thoroughbred horses.

Recently, it was reported that acute hypervolemia improves arterial oxygen tension in human athletes known to experience exercise-induced arterial hypoxemia. Since exercise-induced arterial hypoxemia is routinely observed in racehorses and is known to limit performance, we examined whether pre-exercise induction of acute hypervolemia would similarly benefit arterial oxygenation in maximally exercising thoroughbred horses. Two sets of experiments, namely, placebo [intravenous (IV) physiological saline] and acute hypervolemia (IV 7.2% NaCl, causing an 18.2% expansion of plasma volume) studies were carried out in random order on 13 healthy, exercise-trained thoroughbred horses, 7 days apart. An incremental exercise protocol leading to 120 s of galloping at 14 m s(-1) on a 3.5% uphill incline was used. Galloping at this workload elicited maximal heart rate and induced pulmonary hemorrhage in all horses in both treatments. In the placebo study, arterial oxygen tension decreased to 76.1 (2) mmHg (P<0.0001) at 30 s of maximal exertion, but further significant changes did not occur as exercise duration increased to 120 s [arterial oxygen tension 72.4 (2) mmHg]. A significant arterial hypoxemia also developed in galloping horses in the acute hypervolemia study [arterial oxygen tension at 30 and 120 s was 76.7 (1.7) and 71.9 (1.6) mmHg, respectively], but significant differences between treatments could not be demonstrated. In both treatments, a similar desaturation of arterial hemoglobin was also observed at 30 s of maximal exercise, which intensified with increasing exercise duration as hyperthermia, acidosis and hypercapnia intensified. Thus, acute expansion of plasma volume did not benefit arterial oxygenation in maximally exercising thoroughbred horses.

Preexercise hypervolemia does not affect arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise.

It is reported that preexercise hyperhydration caused arterial O(2) tension of horses performing submaximal exercise to decrease further by 15 Torr (Sosa-Leon L, Hodgson DR, Evans DL, Ray SP, Carlson GP, and Rose RJ. Equine Vet J Suppl 34: 425-429, 2002). Because hydration status is important to optimal athletic performance and thermoregulation during exercise, the present study examined whether preexercise induction of hypervolemia would similarly accentuate the arterial hypoxemia in Thoroughbreds performing short-term high-intensity exercise. Two sets of experiments (namely, control and hypervolemia studies) were carried out on seven healthy, exercise-trained Thoroughbred horses in random order, 7 days apart. In resting horses, an 18.0 +/- 1.8% increase in plasma volume was induced with NaCl (0.30-0.45 g/kg dissolved in 1,500 ml H(2)O) administered via a nasogastric tube, 285-290 min preexercise. Blood-gas and pH measurements as well as concentrations of plasma protein, hemoglobin, and blood lactate were determined at rest and during incremental exercise leading to maximal exertion (14 m/s on a 3.5% uphill grade) that induced pulmonary hemorrhage in all horses in both treatments. In both treatments, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, acidosis, and hyperthermia developed during maximal exercise, but statistically significant differences between treatments were not found. Thus preexercise 18% expansion of plasma volume failed to significantly affect the development and/or severity of arterial hypoxemia in Thoroughbreds performing maximal exercise. Although blood lactate concentration and arterial pH were unaffected, hemodilution caused in this manner resulted in a significant (P < 0.01) attenuation of the exercise-induced expansion of the arterial-to-mixed venous blood O(2) content gradient.

Arterial blood gas control in the upright versus recumbent Asian elephant.

In the elephant, there is concern that lateral recumbency (LR) impairs respiratory muscle and lung function resulting in clinically significant arterial hypoxemia. Using healthy adult female Asian elephants (Elephas maximus, n=6), the hypothesis was tested that, given the O(2) binding characteristics of elephant blood, substantial reductions in arterial O(2) pressure (Pa(O(2))) in LR could be tolerated without lowering arterial O(2) content appreciably. Fifteen minutes of LR decreased Pa(O(2)) from 103+/-2 (upright, U) to 77+/-4 mmHg (P<0.05) and hemoglobin O(2) saturation (U, 97.8+/-0.1, LR, 95.3+/-0.5%, P<0.05). However, due to a recumbency-induced hemoconcentration, arterial O(2) content was unchanged (U, 18.2+/-2.4, LR, 18.3+/-2.1 ml O(2) per 100 ml). In addition, there was a mild hyperventilation in LR that reduced arterial CO(2) pressure (P(CO(2))) from 39.4+/-0.3 to 37.1+/-1.0 mmHg (P<0.05). These data indicate that the Asian elephant can endure at least short periods of LR without lowering arterial O(2) content.

Nitric oxide synthase inhibition does not affect the exercise-induced arterial hypoxemia in Thoroughbred horses.

Because sensitivity of equine pulmonary vasculature to endogenous as well as exogenous nitric oxide (NO) has been demonstrated, we examined whether endogenous NO production plays a role in exercise-induced arterial hypoxemia. We hypothesized that inhibition of NO synthase may alter the distribution of ventilation-perfusion mismatching, which may affect the exercise-induced arterial hypoxemia. Arterial blood-gas variables were examined in seven healthy, sound Thoroughbred horses at rest and during incremental exercise protocol leading to galloping at maximal heart rate without (control; placebo = saline) and with N(omega)-nitro-L-arginine methyl ester (L-NAME) administration (20 mg/kg iv). The experiments were carried out in random order, 7 days apart. At rest, L-NAME administration caused systemic hypertension, pulmonary hypertension, and bradycardia. During 120 s of galloping at maximal heart rate, significant arterial hypoxemia, desaturation of hemoglobin, hypercapnia, hyperthermia, and acidosis occurred in the control as well as in NO synthase inhibition experiments. However, statistically significant differences between the treatments were not found. In both treatments, exercise caused a significant rise in hemoglobin concentration, but the increment was significantly attenuated in the NO synthase inhibition experiments, and, therefore, arterial O(2) content (Ca(O(2))) increased to significantly lower values. These data suggest that, whereas L-NAME administration does not affect pulmonary gas exchange in exercising horses, it may affect splenic contraction, which via an attenuation of the rise in hemoglobin concentration and Ca(O(2)) may limit performance at higher workloads.

Nasal strips do not affect pulmonary gas exchange, anaerobic metabolism, or EIPH in exercising Thoroughbreds.

The present study was carried out to examine whether nasal strip application would improve the exercise-induced arterial hypoxemia and hypercapnia, diminish anaerobic metabolism, and modify the incidence of exercise-induced pulmonary hemorrhage (EIPH) in horses. Two sets of experiments, control and nasal strip experiments, were carried out on seven healthy, sound, exercise-trained Thoroughbred horses in random order, 7 days apart. Simultaneous measurements of core temperature, arterial and mixed venous blood gases/pH, and blood lactate and ammonia concentrations were made at rest, during submaximal and near-maximal exercise, and during recovery. In both treatments, whereas submaximal exercise caused hyperventilation, near-maximal exercise induced significant arterial hypoxemia, desaturation of Hb, hypercapnia, and acidosis. However, O2 content increased significantly with exercise in both treatments, while the mixed venous blood O2 content decreased as O2 extraction increased. In both treatments, plasma ammonia and blood lactate concentrations increased significantly with exercise. Statistically significant differences between the control and the nasal strip experiments could not be discerned, however. Also, all horses experienced EIPH in both treatments. Thus our data indicated that application of an external nasal dilator strip neither improved the exercise-induced arterial hypoxemia and hypercapnia nor diminished anaerobic metabolism or the incidence of EIPH in Thoroughbred horses performing strenuous exercise.

Does significant arterial hypoxemia alter vital signs?

Study Objective: To determine the cardiovascular and respiratory effects of arterial hypoxemia in adult volunteers. Design: Prospective, subject-controlled. Setting: University-affiliated hospital. Subjects: 16 awake, unsedated, unanesthetized adult volunteers. Interventions: Inspired oxygen concentration (FIO 2) was decreased in decrements to reduce pulse oximeter values to a range of 95% to 90%, 89% to 85%, 84% to 80%, and 79% to 70%. Measurements and Main Results: Heart rate, (HR), blood pressure (BP), respiratory rate (RR), arterial blood pH, gas tensions, and oxyhemoglobin saturation were determined during normoxia and each level of oxyhemoglobin desaturation. FI0 2 was reduced from 21% to 10%. Arterial blood oxyhemoglobin saturation and oxygen tension ranged from 100% to 71% and 103 to 35 mmHg, respectively. There were no significant changes in RR, BP, or HR during the study. Conclusions: HR, BP, and RR are not reliable indicators of arterial hypoxemia in awake volunteers. If this finding is also true for sedated or anesthetized patients, then continuous monitoring with pulse oximetry should be used whenever patients are at risk for arterial hypoxemia. Stable HR, BP, and RR may not eliminate the possibility of significant arterial hypoxemia and impending catastrophic events.

The effects of post-treatment with lisofylline, a phosphatidic acid generation inhibitor, on sepsis-induced acute lung injury in pigs.

The effects of lisofylline [(R)-1-(5-hydroxyhexyl)-3,7-dimethylxanthine] (LSF), an inhibitor of de novo phosphatidic acid (PA) generation, on sepsis-induced acute lung injury was studied using Hanford minipigs weighing 18 to 25 kg. Sepsis was induced by an intravenous infusion of Pseudomonas aeruginosa (1 x 10(6)/colony-forming units/kg/min over 2 h). Saline was used as the control vehicle. Six groups were studied: saline control group (SALINE: n = 5); sepsis control group (SEPSIS: n = 5); LSF control group (LSF: n = 5), which received a 25-mg/kgbolus of LSF 30 min before time zero followed by continuous infusion of 10 mg/kg/h throughout the study; LSF-treated septic groups, which were treated with LSF 30 min prior to sepsis (Pre: n = 5), 1 h postonset (Post-1 h: n = 8) or h postonset (Post-2 h: n = 8) of the bacterial infusion. Hemodynamics PaO2, neutrophil counts, and plasma porcine tumor necrosis factor-alpha concentrations were monitored for 6 h. After the minipigs were killed, lung tissue was sampled to measured wet-to-dry weight ratio (W/D), tissue albumin index (TAI), thiobarbituric acid-reactive material content (TBARM), and myeloperoxidase (MPO) activity. Compared with the SALINE group, the SEPSIS group showed significant systemic hypotension, pulmonary hypertension, arterial hypoxemia, neutropenia, and increase in TNF-alpha, MPO activity, W/D, TBARM, and TAI. LSF treatment attenuated sepsis-induced pulmonary hypertension, neutropenia, and hypoxemia, and increased MPO activity and lung injury measurements in the Pre and Post-1 h groups, but its efficacy was blunted in the Post-2 h group. Plasma TNF-alpha was decreased only in the Pre group. Thus, inhibition of intracellular PA generation through de novo pathways attenuates sepsis-induced acute lung injury.

Detection and Correction of Hypoxemia Associated with Air Travel

Hypoxemia occurs during air travel because the pressure in aircraft cabins is not maintained equal to barometric pressure at sea level. Identification of patients who will develop significant arterial hypoxemia is most conveniently achieved by exposing these individuals to inspired oxygen tensions similar to those experienced during air travel. We utilized commercial Venturi devices with nitrogen as a source gas to lower inspired oxygen tensions (114 and 99 mm Hg) to simulate exposure to altitude (6,700 and 10,000 feet) that occurs with air travel. Oxygen was administered by nasal cannulas to correct the induced hypoxemia. Eleven normal subjects had baseline oxygen saturations of 97.3% as determined by ear oximetry. Exposure to reduced oxygen tensions for 20 min using 35 and 40% Venturi devices caused minimal O2 desaturation (94.8 and 93.8%, respectively). Mean baseline arterial oxygen saturation was 93.2% in 11 patients with chronic obstructive lung disease. Oxygen saturation fell to 89.5 and 87.5%, respectively, with exposure to the two levels of reduced oxygen tensions. Hypoxemia was corrected with administration of O2 by nasal cannulas at rates of 1.2 and 1.5 L/min, respectively. We conclude that individual patients can be evaluated conveniently for possible development of hypoxemia associated with air travel using available Venturi devices. This approach also permits determination of the oxygen therapy needed to correct hypoxemia.

Ventilation-perfusion relationships during induced normovolemic polycythemia in dogs.

Previous studies on normal subjects and patients with polycythemia have given conflicting results of the effect of polycythemia on pulmonary gas exchange. We studied acutely induced normovolemic polycythemia in the dog and measured arterial blood gases and ventilation-perfusion (VA/Q) relationships using the multiple inert gas elimination technique. The mean base-line hematocrit of 43 +/- 5% was increased to 57 +/- 4 and 68 +/- 8%, respectively, after two exchange transfusions of packed erythrocytes. Subsequent plasma exchange transfusions returned the mean hematocrit to 44 +/- 4%. Polycythemia caused no significant arterial hypoxemia; indeed there was a slight improvement in the alveolar-arterial PO2 difference. The multiple inert gas elimination measurements showed no increase in VA/Q inhomogeneity with no increase in log SD ventilation (V) or log SD blood flow (Q). There was a shift of mean V and mean Q to high VA/Q areas because of a decrease in cardiac output, presumably caused by increased blood viscosity. This study showed no deleterious effects on pulmonary gas exchange within the hematocrit range of 36-76%.

Postural hypoxemia and erythrocytosis

Seven patients with unexplained erythrocytosis, moderate obesity, and mild hypertension without splenomegaly (Gaisböck's syndrome) were studied. Routine pulmonary studies were normal, but significant arterial hypoxemia was demonstrated in the supine position in all patients. An increase in the serum level of erythropoietin in the supine position was found in five of six patients. Nocturnal oxygen therapy controlled the erythrocytosis in one patient and weight reduction was effective in controlling the hematocrit in another. We were unable to confirm the existence of “Gaisböck's syndrome.” The importance of a complete pulmonary evaluation, including arterial blood gas analysis in the supine position, in all patients with an unexplained erythrocytosis is emphasized. The finding of significant hypoxemia in the supine position in all patients in this study suggests that postural hypoxemia may be a frequent cause of an elevated red cell volume.

Natural history and prognosis of atrial septal defect.

A series of 128 consecutive cases of atrial septal defect in adult patients was analyzed from the standpoint of the course and prognosis. The ages of the patients ranged from 18 to 67 years and the ratio of men to women was 1 to 2. Age distribution when compared with life expectancy tables indicated reduced life expectancy. Clinical analysis revealed that three quarters of the patients were symptomatic, but symptoms were mild to moderate and usually nonprogressive. Hemodynamic analysis revealed significant pulmonary hypertension in 22% of the series, of which 15% had high pulmonary vascular resistance, and significant arterial hypoxemia in 14%. The most serious risk factor in atrial septal defect is severe pulmonary hypertension. This complication, which develops in about 14% of patients with atrial septal defect when they are between 20 and 40 years of age, may be rapidly progressive, leading to shunt reversal, disability, and death. Once established, pulmonary hypertension may progress even when the defect is surgically closed. Heart failure occurs usually in older individuals and is associated mostly with chronic atrial arrhythmias rather than pulmonary hypertension.