MEDLINE Abstracts: Acute Respiratory Distress Syndrome

August 27, 2003

MEDLINE Abstracts: Acute Respiratory Distress Syndrome

What's new concerning acute respiratory distress syndrome? Find out in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape Critical Care.

Vieillard-Baron A, Prin S, Chergui K, Page B, Beauchet A, Jardin F
Intensive Care Med. 2003 Aug 16 [Epub ahead of print]

Objective: Evaluation of low-flow pressure-volume loop at the bedside in ARDS, as an aid to assess recruitment produced by positive end-expiratory pressure (PEEP).
Materials and Methods: Low-flow pressure-volume loop at the bedside were obtained on the first day of respiratory support in 54 successive pulmonary acute respiratory distress syndrome (ARDS) patients (49 of whom had pneumonia) treated between April 1999 and June 2002. From the loop obtained at zero end-expiratory pressure (ZEEP), we determined manually the lower inflexion point (LIP). By superimposing the pressure-volume loop at ZEEP and at PEEP, we evaluated recruitment obtained at a constant elastic pressure of 20 cm H2O.
Results: We observed 2 different types of loops, according to the pattern of the inflation limb. In type 1 (38 cases), the inflation limb was characterized by an inflexion zone, resulting from a progressive or a sudden improvement in compliance. In type 2 (16 patients), the inflation limb was virtually linear, without significant improvement in compliance during inflation, which remained particularly low (26±9 cm H2O). Use of a low PEEP (6±2 cm H2O) produced a substantial recruitment in type-1 patients (74±53 ml), which was marginally improved by a higher PEEP (89±54 ml). In type 2, recruitment produced by PEEP was significantly lower (48±26 ml, P = .006).
Conclusion: Pressure-volume loop at bedside confirmed that a low PEEP was sufficient to obtain recruitment in ARDS. This study also individualized a group of pulmonary ARDS patients exhibiting a markedly reduced compliance, in whom recruitment obtained by PEEP was limited.

Anton N, Joffe KM, Joffe AR
Intensive Care Med. 2003 Aug 16 [Epub ahead of print]

Objective: To (a) describe the experience with high-frequency oscillation (HFO) in children with acute respiratory distress syndrome (ARDS) unresponsive to conventional ventilation; (b) compare observed survival to that predicted by pediatric mortality scores; and (c) determine if oxygenation index changes during HFO can predict survival.
Design: Retrospective, observational study.
Setting: A university hospital pediatric intensive care unit.
Patients: Nineteen children with ARDS (PaO2/FIO2 < 200) unresponsive to conventional ventilation treated with HFO from January 1995 to September 1996.
Interventions: None.
Measurements and Results: The following were recorded: demographic, arterial blood gas and ventilator variables at the time points 0, 6, 12 and 24 h after the start of HFO; PRISM in the first 24 h of admission and pediatric respiratory failure and multiple organ system failure scores on the day of starting HFO. The mortality rate was 26% (5/19). The survival was better than predicted by the Pediatric Respiratory Failure score (P < .01). None of the scores differentiated survivors from non-survivors (P > .25). There was no significant change in oxygenation index over the first 24 hours (P > .18). Of patients with an initial oxygenation index higher than 20 who did not have at least a 20% reduction in oxygenation index by the time 6 hours, 6/9 (67%) survived (sensitivity 75%, specificity 57%).
Conclusions: Survival in pediatric ARDS patients treated with HFO could not be predicted using several outcome scores or the oxygenation index (in the first 24 hours). Survival was significantly better than predicted by the Pediatric Respiratory Failure score. A prospective randomized controlled trial of HFO in ARDS is warranted.

Bindl L, Buderus S, Dahlem P, et al
Intensive Care Med. 2003 Aug 15 [Epub ahead of print]

Male gender predisposes to severe sepsis and septic shock. This effect has been ascribed to higher levels of testosterone. The ESPNIC ARDS database was searched to determine if there was evidence of a similar male preponderance in severe sepsis in prepubertal patients in spite of low levels of male sex hormones at this age. A total of 72 patients beyond neonatal age up to 8 years of age with sepsis were identified. The male/female (M/F) ratio was 1.7 (1.0;2.7) and differed significantly from non-septic ARDS patients in this age group [n = 209; M/F = 1.0 (0.8;1.3)]. The highest M/F-ratio was observed in the first year of life. The gender-ratio was the same as reported in adult patients with sepsis. In infants between 1 month and 12 months of age, the ratio was 2.8 (1.2;6.1) (Chi2 = 5.6; P < .01), in children from 1 year to 8 years of age it was 1.2 (0.7;2.2) (n.s.). In a subgroup of patients with severe sepsis or septic shock, caused by other bacteria than Neisseria meningitidis, the M/F-ratio was 2.1 (1.2;3.6) (Chi2 = 4.9; P < .05); while in patients with meningococcal sepsis (n = 20), the M/F-ratio was 1.0 (0.4;2.3). In prepubertal ARDS patients with sepsis, an increased frequency of male patients is found, comparable to adults. No male preponderance exists in patients with ARDS due to meningococcal septic shock. Since levels of testosterone and other sex hormones are extremely low at this age, we conclude that factors others than testosterone are involved in the male preponderance in severe sepsis.

Petrucci N, Iacovelli W
Cochrane Database Syst Rev. 2003;(3):CD003844

Background: Patients with acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) require mechanical ventilatory support. ALI/ARDS is further complicated by ventilator-induced lung injury. Lung-protective ventilation strategies may lead to improved survival.
Objectives: To assess the effects of ventilation with lower tidal volume (Vt) on morbidity and mortality in adults patients affected by ALI/ARDS. A secondary objective was to determine whether the comparison between low and conventional Vt is different if a plateau airway pressure of greater than 30 to 35 cmH2O was used.
Search Strategy: We searched The Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library issue 3, 2002; MEDLINE (1966 to June 2002); EMBASE and CINAHL (1982 to June 2002); intensive care journals and conference proceedings; databases of ongoing research, reference lists and 'grey literature'.
Selection Criteria: Randomized trials comparing ventilation using lower Vt and/or low airway driving pressure (plateau pressure 30 cm H2O or less), resulting in Vt of 7 ml/kg or less versus ventilation that uses Vt in the range of 10 to 15 ml/kg, in adults (16 year-old or greater).
Data Collection and Analysis: Two reviewers independently assessed trial quality and extracted data. Wherever appropriate, results were pooled. Fixed and random effects models were applied.
Main Results: Five trials, involving 1202 patients, were eligible. The test for heterogeneity gave a P-value of 0.12. Ventilation with lower Vt was associated with a decreased mortality at the end of the follow up period for each trial: 216/605 (35.7%) versus 249/597 (41.7%), relative risk (RR) 0.85 (CI 0.74 to 0.98). The effect of the intervention was not statistically significant when a random effects model was used: RR 0.91 (CI 0.72 to 1.14). Mortality at day 28 was significantly reduced by lung-protective ventilation: RR 0.74 (CI 0.61 to 0.88). The comparison between low and conventional Vt was not significantly different if a plateau pressure less than or equal to 31 cm H2O in control group was used: RR 1.13 (CI 0.88 to 1.45). There was insufficient evidence about morbidity and long-term outcomes.
Reviewer's Conclusions: Clinical heterogeneity, such as different lengths of follow up and higher plateau pressure in control arms in 2 trials make the interpretation of the combined results difficult. Mortality is significantly reduced at day 28 and the effects on long-term mortality are uncertain, although the possibility of a clinically relevant benefit cannot be excluded. There is no evidence that low Vt ventilation is beneficial in patients where hypercapnia is potentially harmful.

Johnston CJ, Rubenfeld GD, Hudson LD
Chest. 2003;124:653-659

Study Objectives: The purpose of this study was to determine the independent effect of age on the risk of developing ARDS in patients with trauma.
Design: Prospective cohort study.
Setting: Level I trauma center.
Measurements and Results: A total of 4,020 consecutive trauma patients who were greater than 12 years of age were identified through the Harborview Medical Center Trauma Registry over a 3-year period. During this time, 484 of the trauma patients (12%) developed ARDS, as identified by the Harborview Medical Center ARDS Registry. Patients who developed ARDS were, on average, older (mean [± SD] age, 44.0 ± 18.8 vs 40.2 ± 20.0 years, respectively; P < .0001) and had higher injury severity scores (23.7 ± 11.3 vs 18.0 ± 10.3, respectively; P < .0001) than trauma patients who did not develop ARDS. The maximum unadjusted odds ratio for developing ARDS was 2.93 (95% confidence interval, 1.91 to 4.50) for the group 60 to 69 years of age compared to the group 13 to 19 years of age. Patients aged ≥ 80 years had an equal risk of developing ARDS compared to those age 13 to 19 years.
Conclusions: Age demonstrated a complex relationship with risk for ARDS development. Older patients showed increasingly higher risks for ARDS development up to 60 to 69 years of age, when the risk for ARDS declined. We concluded that older patients are at significantly greater risk of developing ARDS when compared to younger patients, while the oldest patients may be at less risk.

Mokart D, Guery BP, Bouabdallah R, et al
Chest. 2003;124:644-652

Study Objectives: Neutrophils often have been involved in the pathophysiology of ARDS. However, authentic ARDS has been described in patients with severe neutropenia, suggesting the presence of other potential mechanisms that are responsible of this syndrome. Alveolar macrophages (AMs) could be involved in the development of ARDS, and so we decided to study AM activation in neutropenic patients.
Patients: We designed a prospective study and enrolled 2 subgroups of consecutive patients (group A, 18 patients; group B, 22 patients) with septic ARDS. In the first period, 7 of 18 patients were neutropenic, and in the second period 10 of 22 patients were neutropenic. All neutropenic patients were treated with granulocyte colony-stimulating factor (G-CSF).
Measurements and Results: In group A, bronchoalveolar lavage (BAL) fluid samples were analyzed for differential and total cell counts, and alveolar activation marker expression (ie, human leukocyte antigen [HLA]-DR locus) was determined. Basal and lipopolysaccharide (LPS)-stimulated production of tumor necrosis factor, interleukin (IL)-1beta, IL-6, and IL-10 was evaluated in group B. In neutropenic patients, the BAL fluid total cell count and the neutrophil absolute count were significantly lower compared to those in non-neutropenic patients (P = .029 and P = .046, respectively). HLA-DR expression on AMs was significantly decreased (P = .016), and the percentage of AMs expressing HLA-DR was also significantly lower (P = .041). In neutropenic patients, the mean percentage of AMs expressing HLA-DR was significantly lower in deceased patients compared to survivors (30 ± 7 vs 43 ± 1, respectively; P = .047). Basal AMs released cytokines was comparable between the 2 groups; however, LPS stimulation yielded a deactivation of AMs in neutropenic patients.
Conclusion: These results suggest a deactivation and/or hypoactivation of AMs in septic ARDS patients. This deactivation/hypoactivation could be linked to the use of G-CSF as this molecule has been shown to generate a down-regulation of HLA-DR expression.

Prat G, Renault A, Tonnelier JM, et al
Intensive Care Med. 2003 Aug 6 [Epub ahead of print]

Objective: To evaluate the effects of the humidification device on respiratory, hemodynamic and gas exchange parameters in acute respiratory distress syndrome (ARDS) patients.
Design: A prospective open study.
Setting: A medical intensive care unit of a university hospital. PATIENTS. Acute respiratory distress syndrome patients, with hypercapnia (PaCO2 > 60 mmHg).
Intervention: A progressive reduction of the humidification system dead space (DSh). The following five conditions were tested sequentially: 1. heat and moisture exchanger (internal volume = 95 ml) with a tracheal closed-suction system (internal volume = 25 ml; total DSh = 120 ml); 2. heat and moisture exchanger (internal volume = 45 ml) with the closed-suction system (DSh = 70 ml); 3. heat and moisture exchanger (internal volume = 25 ml) with the closed-suction system (DSh = 50 ml); 4. heated humidifier with the closed-suction system (DSh = 25 ml); and 5. heated humidifier alone (DSh = 0 ml). Recordings were performed at baseline and every 30 minutes after each artificial dead-space reduction. All ventilatory settings remained constant during the measurement periods.
Results: Ten ARDS patients were included. A significant PaCO2 decrease was observed at each humidification system dead-space reduction, compared to baseline: PaCO2 = 80.3 ±20 mmHg at DSh(120) compared to PaCO2 = 63.6 ±13 mmHg at DSh(0) (P < .05). No changes were observed for hemodynamic and ventilatory parameters between the different humidification devices.
Conclusion: Artificial airway dead-space reduction allows a significant PaCO2 reduction. Independently of any respiratory mechanical changes, this very simple maneuver may be of importance when low tidal volume ventilation is used in ARDS patients, and when PaCO2 lowering is warranted.

David M, Weiler N, Heinrichs W, et al
Intensive Care Med. 2003 Jul 25 [Epub ahead of print]

Objective: This study examined whether ARDS patients, in whom predefined ventilator settings fail to maintain oxygenation and CO2 removal, can be safely transitioned to high-frequency oscillatory ventilation (HFOV), and whether HFOV use is efficacious.
Design and Setting: Prospective observational study in the 14-bed intensive care unit of a university hospital.
Patients and Participants: 42 patients with ARDS (APACHE II score 28 [IQR 24-37]) and ventilation time prior HFOV 3.0 days (0.7-9.1).
Measurements and Results: Gas exchange parameters and ventilator data were recorded before and during HFOV treatment (-12 h, -6 h, baseline, 10 min, 1 h, 6 h, 12 h, 24 h). Primary endpoints included: a) PaO2/FIO2 ratio 24 hours after start of HFOV treatment or the last point of measurement if HFOV ended within the first 24 h; b) HFOV-related complications. Post hoc analysis assessed the relationship between outcome and the response to HFOV, and between outcome and time of mechanical ventilation prior to HFOV. At baseline the median PaO2/FIO2 ratio was 95 (IQR 62-129); after 24 h of HFOV the PaO2/FIO2 ratio had increased significantly to 165 (88-225); only one patient developed a unilateral pneumothorax. Of the 42 patients, 18 (43%) had died by day 30. Subset analyses showed a significantly higher 30-day mortality rate in patients with at least 3 days of mechanical ventilation prior to HFOV (64%) and in patients without oxygenation improvement after 24 h on HFOV (71%).
Conclusions: HFOV is an effective and safe method to ventilate ARDS patients. Failure to improve oxygenation within 24 h of HFOV is associated with high mortality.

Long Y, Liu DW, Du B, et al
Zhonghua Jie He He Hu Xi Za Zhi. 2003;26:282-285

Objective: To evaluate the value of static P-V curve under zero end-expiratory pressure (ZEEP) in predicting the effect of sustained inflation (SI) on hemodynamics, oxygenation, and alveolar recruitment in patients with acute respiratory distress syndrome (ARDS).
Methods: Static P-V curve was measured under positive end-expiratory pressure (PEEP) in all the patients 2 h after PEEP was applied. Patients who experienced more than 20% increase in PaO2/FiO2 were considered as responders to SI.
Results: 1. The static P-V curves in responders consistently showed a concave pattern with c-2d ≥ 0 cm H2O (1 cm H2O = 0.098 kpa) and c ≥ 18 cm H2O, while those in non-responders showed a convex pattern with c-2d < 0 cm H2O or c < 18 cm H2O. 2. After SI, decrease of Q(s)/Q(t) (P = .006) was found in responders, but not in non-responders (P = .339). The amount of recruited volume was significantly higher in responders than in non-responders after SI [(241 ± 111) ml vs (29 ± 46) ml, P = .036].
Conclusion: The static P-V curves under ZEEP exhibited different patterns in responders and non-responders to SI in ARDS patients, and may be of value in predicting the response to SI.

Fortenberry JD, Meier AH, Pettignano R, Heard M, Chambliss CR, Wulkan M
J Pediatr Surg. 2003;38:1221-1226

Background: Primary traumatic injury was considered previously a contraindication for institution of extracorporeal life support because of high risk for persistent or new bleeding. Published experience in adults suggests that extracorporeal membrane oxygenation (ECMO) can successfully support trauma victims with pulmonary failure. The authors reviewed their experience with the use of ECMO in pediatric and adult trauma patients with acute respiratory distress syndrome (ARDS) at a children's medical center.
Methods: ECMO Center records from 1991 through 2001 (76 children, 8 adults) were reviewed to identify all patients with a primary or secondary ICD-9 diagnostic code of post-traumatic ARDS in addition to documented trauma.
Results: Five children and 3 adults with traumatic injury and ARDS received ECMO support. Seven patients were injured in motor vehicle collisions; one patient suffered a gunshot wound to the chest. Patient ages ranged from 21 months to 29 years (pediatric median, 4 years; range, 21 months to 18 years). Four patients had pre-ECMO laparotomies, including 3 who required splenectomy. Four patients had liver lacerations, 3 had pulmonary contusions, and 1 had a renal contusion. Median ventilation before ECMO was 6 days (range, 2 to 10). Seven of 8 patients were placed on venovenous (VV) ECMO. Seven patients had significant bleeding on ECMO. Patients were treated with blood product replacement, epsilon-aminocaproic acid (EACA), and aprotinin infusions. Surgical intervention was not required for bleeding. Six patients received hemofiltration. Median time on ECMO was 653 hours (range, 190 to 921 hours). Six of 8 patients overall survived (75%). Four of 5 pediatric patients survived.
Conclusions: Children and adults with severe post-traumatic ARDS can be treated successfully on VV extracorporeal support. Hemorrhage occurs frequently but is manageable.

Reutershan J, Schmitt A, Dietz K, Fretschner R
Clin Sci. 2003 Jul 24 [Epub ahead of print]

In daily routine, information on effective pulmonary blood flow (PBF) is limited and requires invasive monitoring including a pulmonary artery catheter to determine both cardiac output and intrapulmonary shunt. Therefore, we evaluated a non-invasive method for the measurement of PBF in a clinical setting including 12 patients with acute respiratory failure (ARDS) undergoing prone positioning. PBF was determined before (baseline), during and after prone positioning, using a foreign gas rebreathing method with a new photoacoustic gas analyser. Values were compared with cardiac output corrected for intrapulmonary shunt (CO eff). Responders to prone positioning were defined according to the improvement of arterial oxygenation. A total of 84 measurements were performed. PBF values correlated well with COeff (R 2 = 0.96; P < .0001). Bias and limits of agreement (± 2SD) for all measurements were - 0.11 ± 0.76 l/min. At baseline, responders showed significantly lower PBF levels than nonresponders (4.8 ± 1.0 vs. 6.4 ± 1.2 l/min; P = .03). During prone positioning, PBF increased continuously in responders and remained high after patients had been returned to supine. PBF was unaffected in nonresponders. Mean total increase of PBF was 1.2 ± 0.2 l/min in responders vs. - 0.4 ± 0.2 l/min in nonresponders (P < .0001). In conclusion, the investigated rebreathing system allows for a non-invasive determination of PBF at the bedside. The accuracy of the measurements is comparable with the thermodilution method. It is able to reflect changes of PBF induced by prone positioning reliably. Moreover, measuring PBF might be a promising tool to identify responders to prone therapy.

Lew TW, Kwek TK, Tai D, et al
JAMA. 2003;290:374-380

Context: Severe acute respiratory syndrome (SARS) is an emerging infectious disease with a 25% incidence of progression to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) and mortality exceeding 10%.
Objective: To describe the clinical spectrum and outcomes of ALI/ARDS in patients with SARS-related critical illness.
Design, Setting, and Patients: Retrospective case series of adult patients with probable SARS admitted to the intensive care unit (ICU) of a hospital in Singapore between March 6 and June 6, 2003.
Main Outcome Measures: The primary outcome measure was 28-day mortality after symptom onset.
Results: Of 199 patients hospitalized with SARS, 46 (23%) were admitted to the ICU, including 45 who fulfilled criteria for ALI/ARDS. Mortality at 28 days for the entire cohort was 20 (10.1%) of 199 and for ICU patients was 17 (37%) of 46. ICU mortality at 13 weeks was 24 (52.2%) of 46. Nineteen of 24 ICU deaths occurred late (> or =7 days after ICU admission) and were attributed to complications related to severe ARDS, multiorgan failure, thromboembolic complications, or septicemic shock. ARDS was characterized by ease of derecruitment of alveoli and paucity of airway secretion, bronchospasm, or dynamic hyperinflation. Lower Acute Physiology and Chronic Health Evaluation II scores and higher baseline ratios of PaO2 to fraction of inspired oxygen were associated with earlier recovery.
Conclusions: Critically ill patients with SARS and ALI/ARDS had characteristic clinical findings, high rates of complications, and high mortality. These findings may provide useful information for optimizing supportive care for SARS-related critical illness.


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