Elderly versus nonelderly patients with invasive aspergillosis in the ICU: a comparison and risk factor analysis for mortality from the AspICU cohort.

Data regarding the epidemiology and diagnosis of invasive aspergillosis in the critically ill population are limited, with data regarding elderly patients (≥75 years old) even scarcer. We aimed to further compare the epidemiology, characteristics and outcome of elderly versus nonelderly critically ill patients with invasive aspergillosis (IA) Prospective, international, multicenter observational study (AspICU) including adult intensive care unit (ICU) patients, with a culture and/or direct examination and/or histopathological sample positive for Aspergillus spp. at any site. We compared clinical characteristics and outcome of IA in ICU patients using two different diagnostic algorithms. Elderly and nonelderly ICU patients with IA differed in a number of characteristics, including comorbidities, clinical features of the disease, mycology testing, and radiological findings. No difference regarding mortality was found. According to the clinical algorithm, elderly patients were more likely to be diagnosed with putative IA. Elderly patients had less diagnostic radiological findings and when these findings were present they were detected late in the disease course. The comparison between elderly survivors and nonsurvivors demonstrated differences in clinical characteristics of the disease, affected sites and supportive therapy needed. All patients who were diagnosed with proven IA died. Increased vigilance combined with active search for mycological laboratory evidence and radiological confirmation are necessary for the timely diagnosis of IA in the elderly patient subset. Although elderly state per se is not a particular risk factor for mortality, a high SOFA score and the decision not to administer antifungal therapy may have an impact on survival of elderly patients.

Drivers and impact of antifungal therapy in critically ill patients with Aspergillus-positive respiratory tract cultures.

Invasive pulmonary aspergillosis (IPA) is an increasingly recognised problem in critically ill patients. Little is known about how intensivists react to an Aspergillus-positive respiratory sample or the efficacy of antifungal therapy (AFT). This study aimed to identify drivers of AFT prescription and diagnostic workup in patients with Aspergillus isolation in respiratory specimens as well as the impact of AFT in these patients. ICU patients with an Aspergillus-positive respiratory sample from the database of a previous observational, multicentre study were analysed. Cases were classified as proven/putative IPA or Aspergillus colonisation. Demographic, microbiological, diagnostic and therapeutic data were collected. Outcome was recorded 12 weeks after Aspergillus isolation. Patients with putative/proven IPA were more likely to receive AFT than colonised patients (78.7% vs. 25.5%; P <0.001). Patients with host factors for invasive fungal disease were more likely to receive AFT (72.5% vs. 37.4%) as were those with multiorgan failure (SOFA score >7) (68.4% vs. 36.9%) (both P <0.001). Once adjusted for disease severity, initiation of AFT did not alter the odds of survival (HR = 1.40, 95% CI 0.89-2.21). Likewise, treatment within 48 h following diagnosis did not change the clinical outcome (75.7% vs. 61.4%; P = 0.63). Treatment decisions appear to be based on diagnostic criteria and underlying disease severity at the time of Aspergillus isolation. IPA in this population has a dire prognosis and AFT is not associated with reduced mortality. This may be explained by delayed diagnosis and an often inevitable death due to advanced multiorgan failure.

Another case of "European hantavirus pulmonary syndrome" with severe lung, prior to kidney, involvement, and diagnosed by viral inclusions in lung macrophages.

Puumala virus (PUUV) is considered a classic Old World etiologic agent of nephropathia epidemica (NE), or hemorrhagic fever with renal syndrome (HFRS). HFRS is considered to be distinct from hantavirus (cardio-)pulmonary syndrome (HPS or HCPS), described in the New World. Here, we report a severe case, which fulfilled most, if not all, Centers for Disease Control and Prevention (CDC) criteria for HPS, needing non-invasive ventilation and subsequent acute hemodialysis. However, the etiological agent was PUUV, as proved by serological testing, real-time polymerase chain reaction (PCR), and sequencing. Viral antigen was detected by specific anti-PUUV immunostaining, showing, for the first time, greenish intracytoplasmic inclusions in bronchoalveolar lavage (BAL) macrophages. This case definitely confirms that HPS can be encountered during PUUV infections. Interestingly, special findings could render the diagnosis easier, such as greenish homogeneous cytoplasmic inclusions, surrounded by a fine clear halo in BAL macrophages. Therefore, although the diagnosis remains difficult before the onset of renal involvement, the occurrence of severe respiratory failure mimicking community-acquired pneumonia must alert the clinician for possible HPS, especially in endemic areas.

Polyurethane does not protect better than polyvinyl cuffed tracheal tubes from microaspirations.

BACKGROUND: Mechanically ventilated patients are prone to develop ventilator associated pneumonia due to microaspirations of subglottic secretions around the endotracheal tube cuff (usually constructed of polyvinyl material). A novel polyurethane cuff has been designed to minimize these leakages. The aim of the study was to compare the tracheal sealing capacities between the two tubes. METHODS: Twenty-nine consecutive patients from whom tracheal intubation was necessary as part of their care were randomized to receive either a polyvinyl HI-LO Evac® or a polyurethane SEALGUARD Evac® endotracheal tube. Patients requiring emergency intubation, with unstable hemodynamics or history of tracheal/laryngeal disease were excluded. For the entire study, cuff pressure was set at 30 cmH2O, and ventilator parameters were adjusted for a plateau pressure ≤30 cmH2O; Patients were fasting, placed in a strict 45° position during 12 hours and sedated if needed. After injection of 74 MBq 99mTc-DTPA diluted in 5 mL 0.9% NaCl just above the cuff, tracheal radioactivity was assessed sequentially (hourly from T0 to T6, then T8 and T12 hours) using a scintillation camera. RESULTS: Sixteen polyurethane and 13 polyvinyl tubes were compared. Leakages were observed in 11/29 patients (38%) (5/16 polyurethane and 6/13 polyvinyl tubes [P=NS]). Leakages occurred more often in female (7/8) than in male patients (4/21) (P<0.001). Microaspirations were decreased with larger tubes (size 9 vs. ≤8.5: 24% vs. 75%; P=0.01), whatever the cuff membrane. CONCLUSION: These preliminary results suggest that both tubes are poorly effective in preventing microaspirations.

Correlations between cyclosporine concentrations at 2 hours post-dose and trough levels with functional outcomes in de novo lung transplant recipients.

BACKGROUND: Although the reliability of cyclosporine (CyA) concentration at 2 (C2) hours postdosing has been established for kidney, liver, and heart transplant recipients, its use in lung cases remains to be validated. We investigated the relationship between CyA dual time point monitoring and long-term functional outcomes after lung transplantation. METHODS: We included data from 38 lung transplant recipients receiving CyA, azathioprins, and steroids in the study. CyA dosages were based on the trough concentrations. CyA concentrations at 0 (C0) and 2 (C2) hours postdosing were obtained at 1, 2, 3, 6, 9, 12, 15, 18, and 24 months postoperative. We retrospectively compared average CyA level (C0 and C2) during the first 3 posttransplantation months with forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), forced expiratory flow 25%-75 % (FEF 25-75), creatinine, systolic blood pressure (SBP), and diastolic blood pressure (DBP) using regression analysis via generalized estimating equations (GEE). RESULTS: Only improvement in FVC (P = .033) and deterioration of SBP (P < .001) were related to C0 monitoring. No correlation was observed between C0 and FEV1 (P = .13), FEF 25-75 (P = .48), creatinine (P = .07), and DBP (P = .97). Nor was any relationship observed between C2 concentrations and FEV1 (P = .64), FVC (P = .38), FEF 25-75 (P = .09), creatinine (P = .95), SBP (P = .73), or DBP (P = .51). CONCLUSION: There was a lack of a relationship between CyA concentrations (C0 and C2) and functional outcomes among de novo lung transplantations except for a positive correlation of 0 value with long-term improved FVC and increased SBP. This study suggested that C2 determinations may not improving lung recipient management.

Basiliximab as an alternative to antithymocyte globulin for early immunosuppression in lung transplantation.

OBJECTIVE: Basiliximab (BAS), an interleukin-2 monoclonal antibody, has shown promising results as induction therapy in liver and kidney transplantation. We compared the efficacy and patient tolerability of BAS and antithymocyte globulin (ATG) in lung transplantation (LTx). PATIENTS AND METHODS: The study included 37 patients in two groups (ATG and BAS, respectively). The indication for LTx was emphysema in 62.6% of patients in group 1 and 57.1% of patients in group 2. Mean (SD) patient characteristics compared in the two groups included age (52.0 [9.8] vs 54 [10.6] years), height (172.0 [10.1] vs 169 [7.55] cm), and weight (73.9 [15.3] vs 64.4 [14.2] kg) (P = .049). Induction therapy after LTx in the two groups was as follows: in 16 transplantation procedures (eight single and eight bilateral) performed between April 1998 and December 2002, ATG, 3 mg/kg/d for 3 days, was administered, and in 21 transplantation procedures (15 single and 6 bilateral) performed between January 2003 and July 2005, BAS, 20 mg on days 0 and 4, was given. Dosages of cyclosporine, azathioprine, and steroids for maintenance therapy were equivalent in the two groups. We retrospectively compared patient tolerability, occurrence of acute rejection or infection (from bacteria, cytomegalovirus [CMV], or Aspergillus), and outcomes between the two groups during 2 years of follow-up. RESULTS: No cytokine-mediated reaction was observed in either group; however, there was a difference in hematologic effects. On day 2, mean (SD) platelet count was significantly lower in the ATG group at 113,500 (56,400)/mm(3) vs 151,900 (57,300)/mm(3) (P = .046). Because of severe thrombocytopenia, three patients could not be given ATG on day 3. The overall incidence of aspergillosis (18.8% vs 19.0%) and CMV infection (31% vs 57%) was similar in the two groups. However, when the recipient was CMV-positive and the donor was CMV-negative, the there was a clear trend (33.3% vs 88.9%). The number of acute rejection episodes was similar (43.8% vs 52.4%). Survival increased by 20% in the BAS group (P = .03). CONCLUSION: In LTx, safety of BAS use is as good as or better than that of ATG, with no difference in acute rejection episodes or infections, with the possible exception of increased reactivation of CMV infection. Thus, BAS could be an alternative to ATG as induction therapy in LTx; however, further studies are necessary.

Invasive pulmonary aspergillosis in patients with chronic obstructive pulmonary disease.

Aspergillus spp. cultured in specimens from the airways of chronic obstructive pulmonary disease (COPD) patients are frequently considered as a contaminant. However, growing evidence suggests that severe COPD patients are at higher risk of developing invasive pulmonary aspergillosis (IPA), although IPA incidence in this population is poorly documented. Some data report that COPD is the underlying disease in 1% of patients with IPA. Definitive diagnosis of IPA in COPD patients is often difficult as tissue samples are rarely obtained before death. Diagnosis is therefore usually based on a combination of clinical features, radiological findings (mostly thoracic computed tomography scans), microbiological results and, sometimes, serological information. Of 56 patients with IPA reported in the literature, 43 (77%) were receiving corticosteroids on admission to hospital. Breathlessness was always a feature of disease and excess wheezing was present in 79% of patients. Fever (>38 degrees C) was present in only 38.5%. Chest pain and haemoptysis were uncommon. Six out of 33 (18%) patients had tracheobronchitis observed during bronchoscopy. The median delay between symptoms and diagnosis was 8.5 days. The mortality rate was high: 53 out of 56 (95%) patients died despite invasive ventilation and antifungal treatment in 43 (77%) of them. In chronic obstructive pulmonary disease patients, invasive pulmonary aspergillosis currently carries a very poor prognosis. Outcome could perhaps be improved by more rapid diagnosis and prompt therapy with voriconazole.

Combined bronchoalveolar lavage and transbronchial lung biopsy: safety and yield in ventilated patients.

The aim of this study was to evaluate the safety and diagnostic yield of bedside bronchoalveolar lavage (BAL) combined with fibrescopic transbronchial lung biopsy (TBLB) in determining the aetiology of pulmonary infiltrates in mechanically ventilated patients. The records of 38 mechanically ventilated patients who underwent BAL/TBLB to investigate unexplained pulmonary infiltrates were retrospectively reviewed. Patients were divided into two groups: immunocompetent (group 1: n = 22; group 1a: n = 11, late acute respiratory distress syndrome (ARDS); group 1b: n = 11, no ARDS) and immunocompromised (group 2, n=16). The procedure allowed a diagnosis in 28 patients (74%), inducing therapeutic modification in 24 (63%) and confirmation of clinical diagnosis in four (11%). In groups 1a, 1b and 2, diagnosis was obtained in 11 out of 11 (fibroproliferation), seven out of 11 and 10 out of 16 patients, and therapy changed in 11 out of 11 (administration of steroids), six out of 11 and seven out of 16 patients, respectively. Pneumothorax occurred in nine patients (four of group 1a), bleeding in four (<35 mL), and transient hypotension in two. No fatalities were procedure-related. Combined bronchoalveolar lavage/transbronchial lung biopsy is of diagnostic and therapeutic value in mechanically ventilated patients with unexplained pulmonary infiltrates, excluding those with late acute respiratory distress syndrome. Although complications are to be expected, the benefits of the procedure appear to exceed the risks in patients in whom a histological diagnosis is deemed necessary.

Chronic obstructive pulmonary disease patients with invasive pulmonary aspergillosis: benefits of intensive care?

OBJECTIVES: Invasive pulmonary aspergillosis (IPA) is increasingly recognized as a cause of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD) treated with corticosteroids. For these patients admission in intensive care unit (ICU) is often required for life-support and mechanical ventilation. Whether this approach improves outcome is unknown. DESIGN AND SETTING: Retrospective study in a university hospital intensive care unit. PATIENTS: Between November 1993 and December 1997, 23 COPD patients were admitted in our ICU and received antifungal agents for possible IPA. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: The clinical features and the outcome were reviewed. Diagnosis of IPA was classified as confirmed (positive lung tissue biopsy and/or autopsy) or probable (repeated isolation of Aspergillus from the airways with consistent clinical and radiological findings). Among the 23 patients treated for Aspergillus, 16 fulfilling these criteria for IPA were studied. Steroids had been administered at home to all patients but one and were increased during hospitalization in all. Twelve patients suffered a worsening of their bronchospasm precipitating acute respiratory failure. During ICU stay all patients required mechanical ventilation for acute respiratory failure. Although amphotericin B deoxycholate was started when IPA was suspected (0.5-1.5 mg/kg per day), all patients died in septic shock (n = 5) or in multiple-organ failure. CONCLUSIONS: The poor prognosis of intubated COPD patients with IPA, in spite of antifungal treatment suggests that further studies are required to define the limits and indications for ICU management of these patients.

Effect of dopamine on gastrointestinal motility during critical illness.

OBJECTIVE: To document the action of dopamine on gastrointestinal motility in mechanically ventilated patients. DESIGN: Crossover, randomized, placebo-controlled study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS: Twelve mechanically ventilated patients in a stable hemodynamic condition, with no contraindication to enteral feeding. INTERVENTIONS: Dopamine (4 microg/kg per minute) and placebo were infused over 8 h (4 h fasting, followed immediately by 4 h nasogastric feeding at 100 kcal per hour) on two consecutive days, in a random order. Pressure changes in the gastric antrum (four sites) and in the duodenum (two sites) were recorded by perfused catheter manometry. Each session started with the institution of dopamine or placebo infusion. MEASUREMENTS AND RESULTS: The migrating motor complex and its three successive phases were identified (phase I, period of quiescence; phase II, period of irregular contractile activity; phase III or activity front, period of high-frequency, regular contractions). Contractions and activity fronts at each site were quantified during fasting and feeding. The mean duration of the fasting migrating motor complex was determined in the duodenum, as well as the contribution of each phase (phases I, II, III) to the length of the complete cycle. The propagation characteristics of each activity front were assessed visually. The number of contractions was lower in the antrum (p = 0.024) and phase III motor activity higher in the duodenum [incidence of activity fronts (p = 0.008); number of phase III contractions (p = 0.009)] during dopamine infusion than with placebo. These modifications observed under dopamine were related to decreased antral contractions during fasting (p = 0.050), increased incidence of activity fronts during feeding (p = 0.031), and increased number of phase III contractions during fasting (p = 0.037). In both groups (placebo and dopamine) activity fronts rarely started in the antrum, and abnormally propagated activity fronts were found in the duodenum in some patients. CONCLUSIONS: Low-dose dopamine adversely affects gastroduodenal motility in mechanically ventilated critically ill patients.

Repetitive endoscopy and continuous alkaline gastric irrigation in a case of arsenic poisoning.

BACKGROUND: The poor prognosis of patients with persistent gastrointestinal radio-opacities after oral arsenic poisoning supports efficient gastrointestinal decontamination as critical for survival. In a case of massive arsenic ingestion, we performed repetitive gastric endoscopy and a continuous alkaline irrigation of the stomach over several days. CASE REPORT: A 41-year-old woman was admitted 4 hours after intentional ingestion of trivalent arsenic powder 5 g. The admission abdominal X-ray confirmed the presence of multiple gastric opacities. Initial treatment was gastric lavage with normal saline, dimercaprol chelation, and supportive therapy. Since gastric opacities persisted on the abdominal X-ray at 34 hours despite repeated gastric lavage, a gastroscopy was performed showing nonremovable agglomerates. In an attempt to achieve further gastric decontamination, we performed a continuous gastric alkaline irrigation. After 3 days of alkaline irrigation, the abdomen was normal on X-ray but the gastroscopy still showed arsenic concretions. Alkaline irrigation was continued for another 3 days until total disappearance of arsenic agglomerates at the gastroscopy. Admission urinary arsenic was 3663 microg/L. A total of 46.2 mg of inorganic arsenic, or less than 1% the ingested dose, was extracted from the stomach by this technique. The patient was discharged from the intensive care unit 20 days after admission without sequelae.

Effects of the prone position on gas exchange and hemodynamics in severe acute respiratory distress syndrome.

OBJECTIVES: To address the following issues regarding the use of prone position ventilation in patients with severe acute respiratory distress syndrome (ARDS): a) response rate; b) magnitude and duration of improved oxygenation in responders during a 12-hr trial and the consequences of returning to the supine position; c) effects of the prone position on gas exchange and hemodynamics; d) consequences of oxygenation in nonresponders; and e) effects of repeated prone position trials. DESIGN: Prospective, nonrandomized interventional study. SETTING: Medical intensive care unit, university tertiary care center. PATIENTS: Nineteen consecutive, mechanically ventilated patients (age 45+/-20 yrs, mean+/-SD) with ARDS and severe hypoxemia, defined as PaO2/FiO2 of < or = 150 with FiO2 of > or = 0.6 persisting for < or =24 hrs, and a pulmonary artery occlusion pressure of <18 mm Hg. INTERVENTIONS: Patients were turned prone for 2 hrs. Nonresponders were returned supine, but responders were maintained prone for 12 hrs before being returned to the supine position. The procedure was repeated on a daily basis in all patients, until inclusion criteria were no longer met or the patients died. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, blood gas, and gas exchange measurements were performed at the following time points: a) baseline supine; b) after 30 mins prone; and c) after 120 mins prone. Additional measurements for nonresponders were taken after 30 mins supine. For responders, additional measurements were taken after 12 hrs prone and 30 mins supine. Patients were considered responders if an increase in PaO2 of > or = 10 torr (> or =1.3 kPa), or increase in the PaO2/FiO2 ratio of >20 occurred within 120 mins. Eleven (57%) patients responded to the prone position. There was no difference in initial baseline parameters between responders and nonresponders. After 30 mins, the prone position in responders increased PaO2 and decreased calculated venous admixture (Qva/Qt). This improvement was the maximal obtained, and was maintained throughout the 12-hr prone period. After 12 hrs prone, mean FiO2 had been lowered from 0.85+/-0.16 to 0.66+/-0.18 (p < .05). Thirty minutes after the patients were returned supine, PaO2, PaO2/FiO2, and Qva/Qt were not different from 12-hr prone values, and were improved in comparison with baseline supine values. There was no worsening of gas exchange or hemodynamics in nonresponders. After the initial trial, a total of 28 additional episodes of prone position ventilation were performed in nine of the 19 patients. Of the 24 additional episodes in the responders, there was a response in 17 (71%) of 24 episodes. In the four additional episodes in nonresponders, there was a response in only one (25%) of four episodes. Response was accompanied by the same beneficial effects on gas exchange and Qva/Qt and absence of effect on hemodynamics as in the initial trial. There was no worsening in gas exchange or hemodynamics in nonresponder trials. CONCLUSIONS: Based on the data from this study, the prone position can improve oxygenation in severely hypoxemic ARDS patients without deleterious effects on hemodynamics. This beneficial effect does not immediately disappear on return to the supine position. In our patients, an absence of response to this technique was not accompanied by worsening hypoxemia or hemodynamic instability. Repeated daily trials in the prone position should be considered in the management of ARDS patients with severe hypoxemia.

Additive beneficial effects of the prone position, nitric oxide, and almitrine bismesylate on gas exchange and oxygen transport in acute respiratory distress syndrome.

OBJECTIVE: To test the hypothesis that prone position ventilation, nitric oxide, and almitrine bismesylate, each acting by a different mechanism to improve arterial oxygenation, could exert additive beneficial effects when used in combination in patients with severe acute respiratory distress syndrome (ARDS). DESIGN: Prospective, nonrandomized, interventional study. SETTING: Medical and surgical intensive care units at a university tertiary care center. PATIENTS: Twelve patients with ARDS and severe hypoxemia, defined as PaO2/FIO2 of < or = 150 and FIO2 of > or = 0.6, with pulmonary artery occlusion pressure of < 18 mm Hg. INTERVENTIONS: Inhaled nitric oxide (20 parts per million for 15 mins) in the supine and prone position, and intravenous almitrine bismesylate while prone (1 mg/kg/hr for 60 mins), alone or combined with nitric oxide. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, blood gas, and gas exchange measurements were performed at sequential time points as follows: a) baseline supine; b) nitric oxide in the supine position; c) after return to baseline supine; d) after 30 mins prone; e) after 120 mins prone; f) nitric oxide while prone; g) after return to baseline prone; h) almitrine bismesylate prone; and i) nitric oxide and almitrine bismesylate combined, for 15 mins prone. Patients were considered responders to the prone position if a gain in PaO2 of > or = 10 torr (> or = 1.3 kPa) or a gain in the PaO2/FIO2 ratio of > or = 20 was observed. Seven patients (58%) responded to being turned prone. Compared with supine baseline conditions, nitric oxide and supine position increased arterial oxygen saturation from 89 +/- 1 (SD)% to 92 +/- 3% (p < .05) and nitric oxide plus prone position increased arterial oxygen saturation (94 +/- 3% vs. 89 +/- 4%, p < .05) and decreased the alveolar-arterial oxygen difference from 406 +/- 124 torr (54 +/- 15 kPa) to 387 +/- 108 torr (51 +/- 14 kPa) (p < .05). Almitrine bismesylate increased PaO2/FIO2 vs. baseline (122 +/- 58 vs. 84 +/- 21, p < .05). Almitrine bismesylate decreased the alveolar-arterial oxygen difference vs. baseline from 406 +/- 124 torr (53.9 +/- 16.5 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) and vs. nitric oxide and supine position from 406 +/- 111 torr (53.9 +/- 14.7 kPa) to 386 +/- 112 torr (51.3 +/- 14.8 kPa) (p < .05). Prone position alone did not improve oxygenation. However, the combination of nitric oxide and almitrine bismesylate increased PaO2/FIO2 vs. nitric oxide supine and nitric oxide prone conditions (147 +/- 69 vs. 84 +/- 25 and 91 +/- 18, respectively; p < .05). In patients responding to the prone position (n = 7), combining nitric oxide and almitrine bismesylate led to further improvement in PaO2 compared with the prone position alone, with PaO2 increasing from 78 +/- 12 torr (10.3 +/- 1.6 kPa) to 111 +/- 55 torr (14.7 +/- 7.3 kPa) (p < .05), which was not the case when either nitric oxide or almitrine bismesylate was added separately. Heart rate and cardiac output were increased by almitrine bismesylate compared with all other measurements. Mean pulmonary arterial pressure was decreased by nitric oxide (27 +/- 7 vs. 30 +/- 7 mm Hg nitric oxide supine vs. baseline supine and 29 +/- 7 vs. 33 +/- 8 mm Hg nitric oxide prone vs. baseline prone, p < .05) and increased by almitrine bismesylate (36 +/- 9 vs. 30 +/- 7 mm Hg baseline supine, 27 +/- 7 mm Hg nitric oxide supine, 33 +/- 8 mm Hg baseline prone, and 29 +/- 7 mm Hg nitric oxide prone; p < .05). The increase in mean pulmonary arterial pressure was totally abolished by nitric oxide (31 +/- 5 vs. 36 +/- 9 mm Hg, p < .05). Minute ventilation, respiratory system compliance, physiologic deadspace, and PaCO2 remained unchanged. CONCLUSION: In ARDS patients with severe hypoxemia, arterial oxygenation can be improved by combining the prone position, nitric oxide, and almitrine bismesylate, without deleterious effects.

Nitric oxide and prostacyclin as test agents of vasoreactivity in severe precapillary pulmonary hypertension: predictive ability and consequences on haemodynamics and gas exchange.

BACKGROUND: In patients with primary pulmonary hypertension who respond to vasodilators acutely, survival can be improved by the long term use of calcium channel blockers. However, testing for such a response with calcium channel blockers or prostacyclin (PGI2) may cause hypotension and adversely affect gas exchange. Nitric oxide (NO), which does not have these effects, could be a better test agent. METHODS: NO (10, 20, and 40 ppm for 15 minutes), PGI2 (1-->10 ng/kg/min), and oral nifedipine (10 mg, then 20 mg/h) were administered sequentially to 10 patients after determination of the 24 hour spontaneous variability of their pulmonary and systemic mean arterial pressures. Patients were considered responders if the mean pulmonary artery pressure or pulmonary vascular resistance decreased by 20% or more. RESULTS: Six patients (60%) responded to all three agents, and three to none of the agents. One patient responded to PGI2 only. In those who responded to vasodilators, NO had no major effect on gas exchange or systemic haemodynamics, while PGI2 and nifedipine both induced systemic hypotension (mean (SD) systemic arterial pressure 72 (14) versus 89 (19) mm Hg with PGI2 and 72 (15) versus 86 (17) mm Hg with nifedipine, p < 0.05) and hypoxaemia (PaO2 8.7 (1.4) versus 10.8 (1.0) kPa with PGI2 and 8.6 (1.4) versus 10.2 (1.5) kPa with nifedipine, p < 0.05) and increased venous admixture (28 (9) versus 14 (4)% with PGI2 and 22 (9) versus 13 (5)% with nifedipine, p < 0.05). CONCLUSIONS: NO inhalation can accurately predict a vasodilator response to nifedipine in patients with severe pulmonary hypertension without adverse effects on systemic haemodynamics and gas exchange. This absence of side effects may make it a more appropriate agent for testing the vasodilator response.

[Ventilation in the prone position in acute respiratory distress syndrome (ARDS)]. / Ventilation en décubitus ventral lors du syndrome de détresse respiratoire aigu (SDRA).

Prone position mechanical ventilation (PPV) secures an improvement in gas exchange in approximately two-thirds of ARDS patients. Recent experimental and clinical data suggest that PPV acts mainly by recruiting alveoli situated in the dorsal dependent regions which are collapsed under the superimposed weight of the overlying edema-laden lungs. The purpose of this article is to provide an overview of the basic pathophysiological mechanisms underlying PPV as well as to underscore the promising clinical results so far obtained with this technique. In spite of these results the place of PPV among the other ventilatory and pharmacological approaches in the supportive treatment of ARDS, and the possible beneficial or deleterious consequences of associating PPV with one or more of these therapeutic modalities, remains to be determined.