Baseline PaO2 Research Articles

High pressure versus high intensity noninvasive ventilation in stable hypercapnic chronic obstructive pulmonary disease: a randomized crossover trial

BackgroundHigh-intensity (high-pressure and high backup rate) noninvasive ventilation has recently been advocated for the management of stable hypercapnic chronic obstructive pulmonary disease (COPD). However, the relative contributions of high inspiratory pressure and high backup rate to ventilator adherence and physiological outcome have not been investigated.MethodsPatients with stable hypercapnic COPD (daytime PaCO2 > 6 kPa) and nocturnal hypoventilation were enrolled. Patients were randomly allocated to high-pressure and high backup rate (high-intensity) and high-pressure and low backup rate (high-pressure) for a 6-week period. At the end of the first treatment period, patients were switched to the alternative treatment. The primary outcome measure was mean nightly ventilator usage.ResultsTwelve patients were recruited, with seven completing the 12-week trial protocol. The mean patient age was 71 ± 8 years, with a forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) of 50% ± 13% and FEV1 of 32% ± 12%. The baseline PaCO2 and PaO2 were 8.6 ± 1.7 kPa and 7.3 ± 1.4 kPa, respectively. There was no significant difference demonstrated in mean nightly ventilator usage between the high-intensity and high-pressure groups (difference of 4 minutes; 95% confidence interval −45 to 53; P = 0.9). Furthermore, there were no differences in any of the secondary endpoints, with the exception of the respiratory domain of the Severe Respiratory Insufficiency questionnaire, which was lower in the high-intensity arm than in the high-pressure arm (57 ± 11 versus 69 ± 16; P < 0.05).ConclusionThere was no additional benefit, in terms of night-time ventilator adherence or any of the other measured parameters, demonstrated by addition of a high backup rate to high-pressure noninvasive ventilation. These data suggest that it is the high-pressure component of the high-intensity noninvasive ventilation approach that plays the important therapeutic role in the management of hypercapnic respiratory failure in COPD patients.

Abstract 77: Predictive Power of Early Lactate Clearance Regarding 30-Day Neurological Outcome After Cardiac Arrest with Cardiopulmonary Bypass

Objective: Early lactate clearance has been reported to be associated with improved mortality in patients with post cardiac arrest syndrome (PCAS). Recently, cardiopulmonary bypass (CPB) has significantly improved prognosis of those patients, however, it has been still unknown whether early lactate clearance could predict for neurological outcome in PCAS with CPB. We aimed to investigate the usefulness of the early lactate clearance in a cardiac arrest of patients resuscitated and treated with CPB. Methods: Retrospective observational study. Between January 2000 and March 2011, 46 cardiac arrest patients with cardiac causes underwent CPB in a university hospital in Tokyo. Of those, serial arterial lactate concentrations (at ICU admission and 6 hours after ICU admission) were obtained from 21 patients (19 Males, median 61 y/o). Lactate clearance was defined as the percent change after 6 hours from baseline. The patients were divided into two groups (high lactate clearance group or low lactate clearance) by median lactate clearance. Results: The lactate clearance in the high lactate clearance group was 50.3±13.1% (mean±SD) and the low lactate clearance group -14.7±23.9%. There were no significant differences between the groups for demographics, laboratories (except platelets, baseline PaO 2 ), baseline lactate (the high lactate clearance group: 11.3±3.5mg/dl, the low lactate clearance group:10.8±4.2mg/dl), baseline arterial pressure (99.9±41.1mmHg, 96.1±26.7mmHg), use of catecholamine. In the high clearance group, there was significantly higher for favorable CPC (&lt;=2) rate (44% vs 0%, OR 2.8, 95%CI [1.48-5.40]) and Kaplan-Meier survival analysis showed a survival benefit over 30 days (log-rank; p=0.02). Cut-off points with 95% specificity in predicting favorable outcome was 67.4% for early lactate clearance (sensitivity 75%). CONCLUSIONS: Early lactate clearance is specific but only moderately sensitive markers of 30-day neurological outcome. These findings suggest that post arrest tissue hypoperfusion during CPB contributes lactate clearance, regardless CPB.

Severe protein C deficiency is associated with organ dysfunction in patients with severe sepsis

Purpose The aim of this study was to assess the relationship between protein C levels and temporal changes in organ dysfunction. Materials and Methods Using data from the placebo arm of Recombinant Human Activated PROtein C Worldwide Evaluation in Severe Sepsis trial (N = 775), we compared the development of organ dysfunction over time, in adult severe sepsis patients with and without severe protein C deficiency. Results At study enrollment (baseline), patients with and without severe protein C deficiency were similar in age and likelihood of comorbidities. Patients with severe protein C deficiency had lower arterial blood pressure ( P = .0006), greater serum creatinine concentration ( P < .0001), elevated markers of thrombosis and inflammation, and impairment of fibrinolysis ( P < .0001). The baseline PaO 2/FiO 2 ratio was not significantly different between the 2 groups. Seven days after study enrollment, cardiovascular and renal function remained significantly worse in patients with severe protein C deficiency ( P < .0001), and respiratory dysfunction was greater ( P < .0001). Baseline protein C deficiency was seen to be associated with subsequent pulmonary, renal, and hematologic organ failure. Conclusions Severe protein C deficiency in patients with severe sepsis is associated with both the incidence and severity of organ dysfunction and subsequent worsening of organ function and may be a useful predictor of organ failure in severe sepsis.

Patient-Centric LTOT: No Room for Complacency

The benefits of the continuous administration of supplemental long-term oxygen therapy (LTOT) for the amelioration of the sequelae of severe chronic hypoxemia (baseline PaO2 ≤ 55 mg Hg or SpO2 ≤ 88%) secondary to COPD, are well established. When properly prescribed and delivered, LTOT improves

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.

Factors Related to Exertional Oxygen Desaturation in Patients with COPD

Background: The causes of exertional desaturation in patients with COPD can be multifactorial. We aimed to investigate factors predict exertional desaturation in patients with moderate to severe COPD. Methods: We tested 51 consecutive patients with stable COPD (FEV1/FVC, 40±13% predicted). Patients performed a six minute walk test (6MWT). Pulse oxymetric saturation (SpO2) and pulse rate were recorded. Results: Oxygen desaturation was found in 15 subjects after 6MWT, while 36 subjects were not desaturated. Lung diffusing capacity was significantly lower in desaturation (DS) group (62±18% predicted) compared with not desaturated (ND) group (84±20, p＜0.01). However there was no statistical difference of FEV1/FVC ratio or residual volume between two groups. The pulse rate change was significantly higher in the desaturated compared with the not desaturated group. Six minute walking distance, subjective dyspnea scale, airflow obstruction, and residual volume did not predict exertional oxygen desaturation. Independent factors assessed by multiple logistic regression revealed that a pulse rate increment (odd ratio [OR], 1.19; 95% confidence interval [CI], 1.01 ∼1.40; p=0.02), a decrease in baseline PaO2 (OR, 1.105; 95% CI, 1.003∼1.218; p=0.04) and a decrease in lung diffusing capacity (OR, 1.10; 95% CI, 1.01∼1.19; p=0.01) were significantly associated with oxygen desaturation. Receiver operator characteristic (ROC) analysis showed that an absolute increment in pulse rate of 16/min gave optimal discrimination between desaturated and not desaturated patients after 6MWT. Conclusion: Pulse rate increment and diffusion capacity can predict exertional oxygen desaturation in stable COPD patients with moderate to severe airflow obstruction.

2009 H1N1 Influenza and Experience in Three Critical Care Units

We describe futures of ICU admission, demographic characteristics, treatment and outcome for critically ill patients with laboratory-confirmed and suspected infection with the H1N1 virus admitted to the three different critical care departments in Turkey. Retrospective study of critically ill patients with 2009 influenza A(H1N1) at ICU. Demographic data, symptoms, comorbid conditions, and clinical outcomes were collected using a case report form. Critical illness occurred in 61 patients admitted to an ICU with confirmed (n=45) or probable and suspected 2009 influenza A(H1N1). Patients were young (mean, 41.5 years), were female (54%). Fifty-six patients, required mechanical ventilation (14 invasive, 27 noninvasive, 15 both) during the course of ICU. On admission, mean APACHE II score was 18.7±6.3 and median PaO(2)/FIO(2) was 127.9±70.4. 31 patients (50.8%) was die. There were no significant differences in baseline PaO(2)/FIO(2 )and ventilation strategies between survivors and nonsurvivors. Patients who survived were more likely to have NIMV use at the time of admission to the ICU. Critical illness from 2009 influenza A(H1N1) in ICU predominantly affects young patients with little major comorbidity and had a high case-fatality rate. NIMV could be used in 2009 influenza A (H1N1) infection-related hypoxemic respiratory failure.

Efficacy and safety of parenteral omega 3 fatty acids in ventilated patients with acute lung injury

Objective:To determine the effects of parenteral omega 3 fatty acids (10% fatty acids) on respiratory parameters and outcome in ventilated patients with acute lung injury.Measurements and Main Results:Patients were randomized into two groups – one receiving standard isonitrogenous isocaloric enteral diet and the second receiving standard diet supplemented with parenteral omega 3 fatty acids (Omegaven, Fresenius Kabi) for 14 days. Patients demographics, APACHE IV, Nutritional assessment and admission category was noted at the time of admission. No significant difference was found in nutritional variables (BMI, Albumin). Compared with baseline PaO2/FiO2 ratio (control vs. drug group: 199 ± 124 vs. 145 ± 100; P = 0.06), by days 4, 7, and 14, patients receiving the drug did not show a significant improvement in oxygenation (PaO2/FiO2: 151.83 ± 80.19 vs. 177.19 ± 94.05; P = 0.26, 145.20 ± 109.5 vs. 159.48 ± 109.89; P = 0.61 and 95.97 ± 141.72 vs. 128.97 ± 140.35; P = 0.36). However, the change in oxygenation from baseline to day 14 was significantly better in the intervention as compared to control group (145/129 vs. 199/95; P < 0.0004). There was no significant difference in the length of ventilation (LOV) and length of ICU stay (LOS). There was no difference in survival at 28 days. Also, there was no significant difference in the length of ventilation and ICU stay in the survivors group as compared to the non survivors group.Conclusions:In ventilated patients with acute respiratory distress syndrome, intravenous Omega 3 fatty acids alone do not improve ventilation, length of ICU stay, or survival.

Neuromuscular Blockers in Early Acute Respiratory Distress Syndrome

In patients undergoing mechanical ventilation for the acute respiratory distress syndrome (ARDS), neuromuscular blocking agents may improve oxygenation and decrease ventilator-induced lung injury but may also cause muscle weakness. We evaluated clinical outcomes after 2 days of therapy with neuromuscular blocking agents in patients with early, severe ARDS. In this multicenter, double-blind trial, 340 patients presenting to the intensive care unit (ICU) with an onset of severe ARDS within the previous 48 hours were randomly assigned to receive, for 48 hours, either cisatracurium besylate (178 patients) or placebo (162 patients). Severe ARDS was defined as a ratio of the partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FIO2) of less than 150, with a positive end-expiratory pressure of 5 cm or more of water and a tidal volume of 6 to 8 ml per kilogram of predicted body weight. The primary outcome was the proportion of patients who died either before hospital discharge or within 90 days after study enrollment (i.e., the 90-day in-hospital mortality rate), adjusted for predefined covariates and baseline differences between groups with the use of a Cox model. The hazard ratio for death at 90 days in the cisatracurium group, as compared with the placebo group, was 0.68 (95% confidence interval [CI], 0.48 to 0.98; P=0.04), after adjustment for both the baseline PaO2:FIO2 and plateau pressure and the Simplified Acute Physiology II score. The crude 90-day mortality was 31.6% (95% CI, 25.2 to 38.8) in the cisatracurium group and 40.7% (95% CI, 33.5 to 48.4) in the placebo group (P=0.08). Mortality at 28 days was 23.7% (95% CI, 18.1 to 30.5) with cisatracurium and 33.3% (95% CI, 26.5 to 40.9) with placebo (P=0.05). The rate of ICU-acquired paresis did not differ significantly between the two groups. In patients with severe ARDS, early administration of a neuromuscular blocking agent improved the adjusted 90-day survival and increased the time off the ventilator without increasing muscle weakness. (Funded by Assistance Publique-Hôpitaux de Marseille and the Programme Hospitalier de Recherche Clinique Régional 2004-26 of the French Ministry of Health; ClinicalTrials.gov number, NCT00299650.)

Effect of palliative oxygen versus room air in relief of breathlessness in patients with refractory dyspnoea: a double-blind, randomised controlled trial

Palliative oxygen therapy is widely used for treatment of dyspnoea in individuals with life-limiting illness who are ineligible for long-term oxygen therapy. We assessed the effectiveness of oxygen compared with room air delivered by nasal cannula for relief of breathlessness in this population of patients. Adults from outpatient clinics at nine sites in Australia, the USA, and the UK were eligible for enrolment in this double-blind, randomised controlled trial if they had life-limiting illness, refractory dyspnoea, and partial pressure of oxygen in arterial blood (PaO(2)) more than 7.3 kPa. Participants were randomly assigned in a 1:1 ratio by a central computer-generated system to receive oxygen or room air via a concentrator through a nasal cannula at 2 L per min for 7 days. Participants were instructed to use the concentrator for at least 15 h per day. The randomisation sequence was stratified by baseline PaO(2) with balanced blocks of four patients. The primary outcome measure was breathlessness (0-10 numerical rating scale [NRS]), measured twice a day (morning and evening). All randomised patients who completed an assessment were included in the primary analysis for that data point (no data were imputed). This study is registered, numbers NCT00327873 and ISRCTN67448752. 239 participants were randomly assigned to treatment (oxygen, n=120; room air, n=119). 112 (93%) patients assigned to receive oxygen and 99 (83%) assigned to receive room air completed all 7 days of assessments. From baseline to day 6, mean morning breathlessness changed by -0.9 points (95% CI -1.3 to -0.5) in patients assigned to receive oxygen and by -0.7 points (-1.2 to -0.2) in patients assigned to receive room air (p=0.504). Mean evening breathlessness changed by -0.3 points (-0.7 to 0.1) in the oxygen group and by -0.5 (-0.9 to -0.1) in the room air group (p=0.554). The frequency of side-effects did not differ between groups. Extreme drowsiness was reported by 12 (10%) of 116 patients assigned to receive oxygen compared with 14 (13%) of 108 patients assigned to receive room air. Two (2%) patients in the oxygen group reported extreme symptoms of nasal irritation compared with seven (6%) in the room air group. One patient reported an extremely troublesome nose bleed (oxygen group). Since oxygen delivered by a nasal cannula provides no additional symptomatic benefit for relief of refractory dyspnoea in patients with life-limiting illness compared with room air, less burdensome strategies should be considered after brief assessment of the effect of oxygen therapy on the individual patient. US National Institutes of Health, Australian National Health and Medical Research Council, Duke Institute for Care at the End of Life, and Doris Duke Charitable Foundation.

Acute Hypercapnic Respiratory Failure in Patients with Sleep Apneas

Introduction Acute hypercapnic respiratory failure (AHRF) is a serious condition observed in some patients with sleep apnea-hypopnea syndrome (SAHS). The objective of the present study was to study the clinical characteristics of SAHS patients who develop AHRF and their prognosis. Patients and method A total of 70 consecutive SAHS patients who survived an AHRF episode and 70 SAHS patients paired by age with no previous history of AHRF were prospectively studied and followed up for 3 years. Results The deterioration of lung function due to obesity or concomitant chronic obstructive pulmonary diseases (COPD) was common in SAHS patients with AHRF. In the multivariate analysis, the risk factors associated with AHRF were baseline PaO 2, the theoretical percentage value of the forced vital capacity, alcohol consumption, and benzodiazepines. The mortality during follow up was higher among patients who had AHRF than in the control group. The main cause of death was respiratory, and the coexistence of COPD was identified as a mortality risk factor. Conclusions The development of AHRF in SAHS patients is associated with a deterioration in lung function and with alcohol and benzodiazepine consumption. The patients had a higher mortality after the AHRF episode, mainly a respiratory cause. New studies are required that evaluate the different available therapeutic options in these patients.

Six minute walking test: an old tool with new applications

Six minute walking test: an old tool with new applications

Air by Cannula Passes End-of-Life Test

AUSTIN, TEX. — Palliative oxygen was no better than air delivered by a nasal cannula for relieving dyspnea or improving quality of life in a study of 239 non- or mildly hypoxemic elderly patients with terminal illness. During the first 24 hours, patients in the O2 Breathe Trial had an improvement of about 10% in dyspnea symptoms with either treatment, or 1 point on a 10-point self-reported scale. The results were sustained over the 7-day study period, lead investigator Amy Abernethy, MD, and her associates reported at the annual meeting of the American Academy of Hospice and Palliative Medicine. For the study, patients with intractable dyspnea received ordinary air or palliative oxygen, which combined air with an increased oxygen concentration of up to 28%. Both treatments were given via nasal cannula from a blinded concentrator at 2 L per minute for at least 15 hours per day. The patients' mean age was 73 years, 62% were male, 64% had COPD, and 16% had cancer. Regardless of treatment group, patients with worse breathlessness at baseline were more likely to respond, said Dr. Abernethy, an oncologist and co-chair of the Duke Cancer Care Research Program at Duke University Medical Center in Durham, N.C. After 7 days of treatment, the mean change from baseline in dyspnea symptoms was 1 point for patients with moderate dyspnea (baseline 4-6 points), compared with 2.5 for those with severe dyspnea (baseline 7-10 points). The findings call into question whether it's necessary to prescribe palliative oxygen in these patients and suggest that giving air via a nasal cannula is just as good, Dr. Abernethy said. Palliative oxygen is widely used to treat breathlessness, which affects up to 70% of patients with cancer and 90% of those with chronic obstructive pulmonary disease (COPD) and tends to worsen as death nears. Dr. Abernethy noted that her hospice spends $250,000 per month on oxygen and oxygen concentrators in order to provide palliative oxygen. “The most important piece in translation is focusing on which patients are likely to get the most benefit,” Dr. Abernethy said. “Clearly, it's the patient who is most dyspneic and clearly [the benefits are seen] in the first 24 hours. Whether you should use oxygen or air delivered by nasal cannulae doesn't seem to matter.” She added in an interview that it's hard to prescribe just ordinary air for terminally ill patients suffering from dyspnea. She noted that recommendations for palliative oxygen vary by guideline group and country. However, the survival benefit of oxygen therapy is well established for severely hypoxic COPD patients (PaO2 of 55 mm Hg or less). A trial is underway to evaluate the use of forced-air fans for treating dyspnea, she said. Also, a review of 47 studies in 2,532 patients with breathlessness and advanced stages of malignant and nonmalignant diseases (mostly COPD) concluded that acupuncture/acupressure could be helpful, but the review could not judge the evidence for fans, music, relaxation, counseling, and psychotherapy (Cochrane Database Syst. Rev. 2008. CD005623 [DOI:10.1002/14651858]). The O2 Breathe Trial recruited patients with a baseline PaO2 greater than 55 mm Hg from nine sites in Australia, the United Kingdom, and the United States. The trial was adequately powered, Dr. Abernethy said, but she noted that it did not have a placebo arm and did not use pulse oximetry. Baseline O2 saturation was 94% to 95%. PaO2 was measured only at baseline (mean 77 mm Hg). In linear regression analyses, patients receiving oxygen therapy were almost twice as likely to have a morning response as were those receiving air (odds ratio 1.86). The O2 Breathe Trial was funded by the National Institute on Aging, Australia's National Health and Medical Research Council, the Doris Duke Charitable Foundation, and the Duke Institute for Care at the End of Life. Patrice Wendling is with the Chicago bureau of Elsevier Global Medical News. Although this study utilized only a 2-liter standard oxygen flow rate and is hardly conclusive, it raises interesting questions. First, should we start purchasing machines that just blow room air? Is the response to air via nasal cannula in this study just a placebo effect, or is it the airflow itself? Oxygen is expensive, but certainly our palliative care patients deserve to be made as comfortable as possible with interventions that are not harmful.

Extending the preoxygenation period from 4 to 8 mins in critically ill patients undergoing emergency intubation*

To determine the effectiveness of increasing the preoxygenation period with 100% oxygen in the critically ill patient from 4 to 8 mins in preparation for emergency tracheal intubation. Nonrandomized, controlled trial. Large, level one trauma center, tertiary care intensive care unit. Critically ill patients failing noninvasive respiratory support techniques who required tracheal intubation followed by mechanical ventilation. A baseline arterial blood gas was obtained on noninvasive passive therapy and at 4, 6, and 8 mins of active preoxygenation efforts with 100% oxygen therapy with a noncollapsing resuscitator bag and mask. Best effort to achieve a tight fitting mask seal was pursued coupled with other mask ventilation maneuvers to optimize noninvasive oxygenation and ventilation. Thirty-four patients consecutively intubated by the author during the 7-month study period were studied. The baseline PaO2 (mean +/- SD) with concurrent noninvasive support was 61.9 +/- 14.6 mm Hg (range: 44-109 mm Hg) and increased a mean of 22 mm Hg to 83.8 +/- 51.5 mm Hg after 4 mins of preoxygenation (p < 0.01). Continued preoxygenation efforts (6 mins) increased the PaO2 to 88.2 mm Hg +/- 48.5 and after 8 mins to 92.7 mm Hg +/- 55.2. At the 8-min mark, 5 of 34 patients achieved > 10% increase in their PaO2 and only two patients increased their 4-min PaO2 by > or = 50 mm Hg after the additional 4 mins of preoxygenation. One quarter of the patients experienced a reduction in their PaO2 from the 4 to the 8-min time period. Nearly, 50% of the patients met the criteria for desaturation during the intubation procedure. Extending the preoxygenation period from the customary 4 mins to either 6 or 8 min seems to be marginally effective in the majority of patient suffering from cardiopulmonary deterioration and such an extension may jeopardize oxygenation efforts in some patients.

Enhanced exercise‐induced plasma cytokine response and oxidative stress in COPD patients depend on blood oxygenation

In healthy subjects, hypoxemia and exercise represent independent stressors promoting the exercise-induced cytokine response and oxidative stress. We hypothesized that hypoxemia in patients with chronic obstructive pulmonary disease (COPD) may affect the cytokine production and/or the changes in oxidant-antioxidant status in response to maximal exercise. Exercise-induced changes in PaO2 allowed to transiently increase or decrease baseline hypoxemia and to point out its specific action on muscle metabolism. COPD patients with severe to moderate hypoxemia (56 < PaO2 < 72 mmHg) performed an incremental cycling exercise until volitional exhaustion. Two cytokines [interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha] and three blood indices of oxidative stress [plasma thiobarbituric acid reactive substances (TBARS) and two antioxidants, reduced erythrocyte glutathione (GSH), and reduced plasma ascorbic acid, RAA] were measured at rest, then during and after exercise. The changes in the cytokine levels and oxidant-antioxidant status were analysed in relation with the baseline PaO2 and its exercise-induced variations. Data were compared with those obtained in an age- and body mass index-matched group of healthy subjects. Compared with healthy subjects, COPD patients presented a marked accentuation of exercise-induced increase in IL-6 level and earlier changes in their oxidant-antioxidant status. Resting levels of IL-6 and TNF-alpha and exercise-induced peak variations of TBARS, IL-6 and TNF-alpha were negatively correlated with the baseline PaO2. In COPD patients, the peak increases in IL-6 and TBARS were attenuated when exercise hyperventilation reduced the baseline hypoxemia. Our study indicates that the PaO2 level affects both the exercise-induced oxidative stress and cytokine response in hypoxemic COPD patients.

Hepatopulmonary syndrome: an emerging complication in HIV-hepatitis C virus co-infected patients

Following the availability of highly active antiretroviral therapy (HAART), chronic liver disease now represents the major cause of morbidity and mortality for HIV-infected patients [1,2]. Among the wide spectrum of end-stage liver disease complications, hepatopulmonary syndrome (HPS) has not been described. We report a fatal case of HPS in a woman with HIV and Child–Pugh B cirrhosis due to hepatitis C virus (HCV). A 40-year-old psychotic woman, who had been followed up for a HIV/HCV co-infection over a period of 10 years, presented at our institution complaining of dyspnoea for 2 weeks. She had interrupted her antiretroviral therapy a year earlier. Her CD4 cell count was 22 cells/μl and her HIV-RNA viral load was 88 000 copies/ml. At presentation, with a temperature of 37°C and a respiratory rate of 25/min, she was cyanotic with clubbing of the fingers. She had hepatomegaly and stigmata of portal hypertension (spider angiomas, splenomegaly). Fine crackles could be heard over both lungs. Analysis (on room air) of arterial blood gases withdrawn while the patient was in a supine position showed hypoxemia (arterial partial pressure of oxygen (PaO2) was 50 mmHg and the arterial partial pressure of carbon dioxide (PaCO2) was 40 mmHg). The arterial blood gases worsened upon standing (PaO2, 42 mmHg; PaCO2, 39.3 mmHg) suggesting orthodeoxia. Blood testing showed the following values: haemoglobin, 12.6 g/dl and platelets, 40 000/μl. The serum transaminases were elevated; serum conjugated bilirubin was 30 μmol/l (normal range, < 17 μmol/l); albumin was low with a value 19 g/l (normal range, 35–45 g/l); and the prothrombin time was 51% (normal range, 75–100%). The serum brain natriuretic peptide level was normal. Microscopic examination and culture of sputum and broncho-alveolar lavage were negative for Pneumocystis jirovecii and other opportunistic pathogens. Chest radiographs showed bilateral basilar reticulonodular opacities and normal lung volumes. Pulmonary computerized tomographic angiography with contrast revealed no evidence of pulmonary emboli. Pulmonary function testing demonstrated a reduced carbon monoxide diffusion capacity. The presence of delayed contrast appearance in the left heart on contrast-enhanced echocardiocardiography confirmed the diagnosis of HPS. Continuous home oxygen therapy (6 l/min) and a new antiretroviral therapy regimen were initiated. After initial improvement of the dyspnoea, she died of a urinary sepsis 3 months later. Hepatopulmonary syndrome is defined as a triad of chronic liver diseases, hypoxemia < 70 mmHg and pulmonary vascular dilation [3]. The estimated prevalence of HPS in patients with chronic liver disease varies between 4 and 29% according to the heterogeneous criteria used for definition of the condition [3,4]. In a recent study among patients with hepatitis B or C infection, the reported prevalence was 1.1% [5]. Little data is available on HIV-infected patients as only two cases have previously been reported in the literature [6,7]. The mechanisms leading to pulmonary vasodilation are complex and multifactorial. There appears to be an imbalance between the vasodilating and vasoconstricting mediators (nitrogen monoxide and endothelin-1). Hypoxemia can be explained by anatomical shunting and a diffusion–perfusion abnormality [3,4,6]. HPS occurs mainly but not exclusively in cirrhotic patients with portal hypertension [3,4]. This increasingly frequent complication is characterized by a delayed diagnosis with a mean duration of respiratory symptoms of 4.8 years before diagnosis. The presence of hypoxemia associated with platypnea and orthodeoxia (decrease in PaO2 > 3 mmHg in the erect position) as in our observation is suggestive of clinically significant HPS [3,4,6,7]. When the diagnosis is suspected, analyses of arterial blood gases should be obtained in both erect and supine positions. Attention in daily practice should be drawn to the presence of basilar interstitial infiltrates on chest radiographs, mimicking interstitial lung diseases or opportunistic pulmonary infections. Moreover, a high-resolution computerized tomography scan of the chest is useful to rule out other causes of hypoxemia and confirm the vascular etiology (dilated lung vessels) of the opacities [8]. Contrast-enhanced echocardiography is the key diagnostic tool [3,4]. HPS represents a significant mortality risk factor (overall mortality of 41% at 3 years after onset of dyspnoea) among cirrhotic patients, even after transplantation [9]. The most relevant prognosis factor is severe hypoxemia, with a baseline PaO2 < 50 mmHg associated with high mortality [10]. Currently, there is no effective medical treatment (methylene blue, inhaled NO, garlic, norfloxacin) for HPS [4,6,9,11]. Orthotopic liver transplantation (OLT), an emerging practice in selected HIV/HCV co-infected patients, is the only efficient treatment since it can reverse oxygenation abnormalities [11–13]. No data is available yet in this group. Thus, HPS should be considered in every case of a HIV patient with associated liver disease, presenting with an unexplained dyspnoea and hypoxemia. Early detection of ‘subclinical HPS’ by systematic arterial blood gas measurements in HIV-associated liver disease improves the prognosis.

Effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome

To study the effect of oral garlic on arterial oxygen pressure in children with hepatopulmonary syndrome. Garlic powder in a capsule form was given to 15 children with hepatopulmonary syndrome (confirmed by contrast echocardiography) at the dosage of 1 g/1.73 m(2) per day. Patients were evaluated clinically and by arterial blood gas every four weeks. The garlic capsule was administered to 15 patients with hepatopulmonary syndrome. There were 10 boys and 5 girls with a mean age of 9.4+/-3.9 years. The underlying problems were biliary tract atresia (4 patients), autoimmune hepatitis (4 patients), cryptogenic cirrhosis (4 patients) and presinusoidal portal hypertension (3 patients). Eight patients(53.3%) showed an increase of 10 mmHg in their mean arterial oxygen pressure. The baseline PaO(2) was 65.6+/-12.1 mmHg in the responder group and 47.1+/-11.2 mmHg in non-responder group. At the end of treatment the mean PaO(2) in responders and non-responders was 92.2+/-7.75 mmHg and 47.5+/-11.87 mmHg, respectively (P<0.01). Garlic may increase oxygenation and improve dyspnea in children with hepatopulmonary syndrome.

Preoxygenation in critically ill patients requiring emergency tracheal intubation*

To determine the effectiveness of preoxygenation with 100% oxygen in the critically ill patient in preparation for emergency tracheal intubation. Nonrandomized, controlled trial. Large, level 1 trauma center, tertiary care intensive care unit. Critically ill patients failing noninvasive respiratory support techniques who require tracheal intubation followed by mechanical ventilation. A baseline arterial blood gas was obtained on noninvasive therapy and 4 mins post-100% oxygen therapy with a bag-mask assembly. Best effort to achieve a tight-fitting mask seal was pursued coupled with other mask ventilation maneuvers to optimize noninvasive oxygenation and ventilation. A total of 42 patients consecutively intubated during the 15-month study period were studied. The baseline Pao2 (mean +/- sd) with concurrent noninvasive support was 67 +/- 19.6 mm Hg (range, 43-88 mm Hg) and increased a mean of 37 mm Hg to 103.8 +/- 63.2 mm Hg after 4 mins of preoxygenation with 100% oxygen. A total of 36% of patients had minimal changes (+/-5%) in their baseline Pao2, and only 19% increased their baseline Pao2 by at least 50 mm Hg after preoxygenation maneuvers. The critically ill patient has little reserve to tolerate interruption of oxygen delivery and, thus, is at risk for hypoxemia during emergency airway management. Preoxygenation efforts as described in this clinical trial appear to be marginally effective in regard to providing a reasonable safeguard against hypoxemia during laryngoscopy and endotracheal intubation.

Natural history of hepatopulmonary syndrome

Few data exist concerning survival after the diagnosis of hepatopulmonary syndrome (HPS). Although orthotopic liver transplantation (OLT) frequently results in complete resolution of HPS, the relationship between transplantation and survival has not been described. The study rationale was to describe long-term survival in patients with HPS. Data were derived from patients diagnosed with HPS at Mayo Clinic (n = 61) between 1985 and 2002, including those undergoing OLT (n = 24) and those who did not (n = 37). A case-control, Kaplan-Meier survival analysis between HPS patients and 77 patients without HPS matched for liver disease cause, model for end-stage liver disease (MELD), severity of liver disease by the Child classification, and age was described for OLT and non-OLT groups. Patients with HPS had a mean partial pressure of arterial oxygen (PaO(2)) decline of 5.2 + 2.3 mm Hg per year awaiting OLT. For HPS patients, despite similar baseline PaO(2), brain uptake of technetium macroaggregated albumin ((99m)TcMAA), or measures of hepatic dysfunction, 5-year survival associated with OLT was 76% versus 23% who did not undergo transplantation (P < .0001). Comparing those who did not undergo transplantation, HPS patients had worse 5-year survival than matched controls (P = .0003). However, reasons to deny OLT (comorbidity) in the setting of HPS may well have contributed to observed survival differences. Baseline PaO(2) </=50 mm Hg was associated with worse survival irrespective of the decision to perform OLT. In conclusion, hypoxemia of HPS is frequently progressive. As OLT outcome relates to pretransplantation PaO(2), additional MELD points should advance the priority for OLT in HPS.

Utilizing the peritoneum for gas exchange with oxygenated perfluorocarbons

Introduction: This pilot study attempted to determine if it was possible to deliver a clinically significant amount of oxygen to a large animal, with induced hypoxia, by perfusing the abdomen with oxygenated perfluorocarbons. Methods: 15 pigs weighing 45 to 55 kg were rendered hypoxic by ventilating them with a blend of nitrogen and oxygen to achieve sub-atmospheric inspired oxygen concentrations (FiO2) ranging from 18–10%, resulting in baseline arterial oxygen pressures (PaO2) of 65.9 ± 9.7 mmHg to 26.6 ± 2.8 mmHg, respectively. Peritoneal perfusion was then performed in 8 animals with oxygenated perfluorocarbon and 7 with oxygenated saline. This study was approved by the IACUC. Results: The average increase in PaO2 with oxygenated perfluorocarbon perfusion ranged from 8.1 to 18.2 mmHg. A common treatment effect of 12.8 mmHg (95% CI = 7.4 to 18.2; p-value < 0.001) was estimated across all FiO2 values, representing the average mean difference in oxygen uptake between PFC and saline when oxygenation was on, irrespective of the level of FiO2. The most clinically relevant results occurred at a FiO2 of 14%, resulting in a baseline PaO2 of 39.4 ± 5.0 mmHg, but increasing to 55.3 ± 7.6 mmHg with oxygenated perfluorocarbon perfusion. Control experiments with oxygenated saline did not demonstrate any significant gas exchange effects. Conclusions: The peritoneal cavity can be used for gas exchange and, in our model, yielded clinically relevant quantities of supplemental oxygen. This technique may have potential for supportive care of patients dying from hypoxia in the setting of a reversible lung injury.