Klaus Lewandowski

Epidemiology and outcome of acute lung injury in European intensive care units. Results from the ALIVE study

ObjectivesTo re-examine the epidemiology of acute lung injury (ALI) in European intensive care units (ICUs).Design and settingA 2-month inception cohort study in 78 ICUs of 10 European countries.PatientsAll patients admitted for more than 4xa0h were screened for ALI and followed up to 2xa0months.Measurements and main resultsAcute lung injury occurred in 463 (7.1%) of 6,522 admissions and 16.1% of all mechanically ventilated patients; 65.4% cases occurred on ICU admission. Among 136 patients initially presenting with “mild ALI” (200< PaO2/FiO2 ≤300), 74 (55%) evolved to acute respiratory distress syndrome (ARDS) within 3xa0days. Sixty-two patients (13.4%) remained with mild ALI and 401 had ARDS. The crude ICU and hospital mortalities were 22.6% and 32.7% (p<0.001), and 49.4% and 57.9% (p=0.0005), respectively, for mild ALI and ARDS. ARDS patients initially received a mean tidal volume of 8.3±1.9xa0ml/kg and a mean PEEP of 7.7±3.6xa0cmH2O; air leaks occurred in 15.9%. After multivariate analysis, mortality was associated with age (odds ratio (OR) =1.2 per 10xa0years; 95% confidence interval (CI): 1.05–1.36), immuno-incompetence (OR: 2.88; Cl: 1.57–5.28), the severity scores SAPS II (OR: 1.16 per 10% expected mortality; Cl: 1.02–1.31) and logistic organ dysfunction (OR: 1.25 per point; Cl: 1.13–1.37), a pH less than 7.30 (OR: 1.88; Cl: 1.11–3.18) and early air leak (OR: 3.16; Cl: 1.59–6.28).ConclusionsAcute lung injury was frequent in our sample of European ICUs (7.1%); one third of patients presented with mild ALI, but more than half rapidly evolved to ARDS. While the mortality of ARDS remains high, that of mild ALI is twice as low, confirming the grading of severity between the two forms of the syndrome.

High survival rate in 122 ARDS patients managed according to a clinical algorithm including extracorporeal membrane oxygenation.

Abstract Objective: We investigated whether a treatment according to a clinical algorithm could improve the low survival rates in acute respiratory distress syndrome (ARDS). Design: Uncontrolled prospective trial. Setting: One university hospital intensive care department. Patients and participants: 122 patients with ARDS, consecutively admitted to the ICU. Interventions: ARDS was treated according to a criteria-defined clinical algorithm. The algorithm distinguished two main treatment groups: The AT-sine-ECMO (advanced treatment without extracorporeal membrane oxygenation) group (n = 73) received a treatment consisting of a set of advanced non-invasive treatment options, the ECMO treatment group (n = 49) received additional extracorporeal membrane oxygenation (ECMO) using heparin-coated systems. Measurements and results: The groups differed in both APACHE II (16 ± 5 vs 18 ± 5 points, p = 0.01) and Murray scores (3.2 ± 0.3 vs 3.4 ± 0.3 points, p = 0.0001), the duration of mechanical ventilation prior to admission (10 ± 9 vs 13 ± 9 days, p = 0.0151), and length of ICU stay in Berlin (31 ± 17 vs 50 ± 36 days, p = 0.0016). Initial PaO2/FIO2 was 86 ± 27 mm Hg in AT-sine-ECMO patients that improved to 165 ± 107 mm Hg on ICU day 1, while ECMO patients showed an initial PaO2/FIO2 of 67 ± 28 mm Hg and improvement to 160 ± 102 mm Hg was not reached until ICU day 13. Q˙S/Q˙T was significantly higher in the ECMO-treated group and exceeded 50 % during the first 14 ICU days. The overall survival rate in our 122 ARDS patients was 75 %. Survival rates were 89 % in the AT-sine ECMO group and 55 % in the ECMO treatment group (p = 0.0000). Conclusions: We conclude that patients with ARDS can be successfully treated with the clinical algorithm and high survival rates can be achieved.

Exhaled nitric oxide in preterm infants

Nitric oxide (NO) is detectable in the exhaled gas of adults during spontaneous respiration and, according to current knowledge, mainly originates from the paranasal sinuses. We studied total NO excretion rates by chemiluminescence in preterm infants whose paranasal sinuses are known to be only partially pneumatized. NO excretion was 7.15 +/- 1.13 nl/min (mean +/- SD, range 6.33-9.36 nl/min) measured from spontaneously exhaled nasal gas (n = 6) and 0.3 +/- 0.05 nl/min (range 0.26-0.36 nl/min) measured from the lower airways in intubated individuals (n = 3). These values are considerably lower than those reported for older children and adults. Body weight-related amounts of NO excretion, however, seem comparable between infants and adults.

Evidence of nitric oxide in the exhaled gas of Asian elephants (Elephas maximus).

Nitric oxide (NO) produced in the respiratory tract is released into the respiratory gases of humans, rabbits, guinea-pigs, and rats. We analysed the NO concentrations in the exhaled gas of four awake Asian elephants. Two methods were employed: (1) exhaled gas was sampled from the elephants trunks with a 1 L syringe and analysed for NO concentrations by chemiluminescence; (2) respiratory gas was continuously aspirated via a thin plastic tube positioned within the trunk and on-line analysed for NO concentrations by chemiluminescence. Syringe sampling (n = 4), when corrected for dilution by ambient air using linear regression analysis, revealed a mean NO concentration of 31 parts per billion (ppb); highest exhalatory concentrations measured during continuous suctioning were 27 and 28 ppb (n = 2). The exhaled NO concentrations in elephants are similar to those found in humans measured with a comparable technique. This supports the hypothesis that a size-independent normal value of endogenous NO is provided in the airways which may contribute to regulation of pulmonary ventilation and perfusion by autoinhalation in some mammals.

Nasal, pulmonary and autoinhaled nitric oxide at rest and during moderate exercise.

Objective: To investigate nasal nitric oxide (NO) excretion, pulmonary NO excretion, and autoinhalation of nasally released NO at rest compared with that during moderate exercise in smokers and non-smokers.¶Design: Prospective observational study.¶Setting: University laboratory.¶Participants: Fourteen healthy adult volunteers.¶Interventions: Breathing of NO-purified air supplied via a tube system at rest and during a bicycle-ergometer workload of 60 Watt over a time of 10 min.¶Measurement and results: We examined nasal and pulmonary NO excretion in smoking (n = 7) and non-smoking (n = 7) adult human volunteers. At rest, we measured constant nasal NO excretion rates of 311 ± 89 nl/min for non-smokers and 261 ± 142 nl/min for smokers (mean ± SD, n. s.). During 60 W exercise, nasal NO release remained unchanged, while pulmonary NO excretion doubled compared with the rates at rest (non-smokers: 40 ± 21 nl/min versus 23 ± 14 nl/min, p < 0.05; smokers: 41 ± 8 nl/min versus 22 ± 8 nl/min, p < 0.05). The differences between smokers and non-smokers in nasal or pulmonary NO excretion were not significant. To determine the autoinhaled amount of nasally released NO, we also measured the NO concentration within the nasopharynx of five volunteers during nasal breathing. The average inhaled NO concentration was 17.8 ± 3.1 ppb at rest and this decreased to 9.3 ± 1.8 ppb during exercise of 60 W, while minute ventilation approximately doubled from 9 ± 2 to 21 ± 3 l/min.¶Conclusion: Our results demonstrate that moderate exercise increased exclusively pulmonary NO excretion. Nasal NO release, which is 10 times higher at rest, was not changed. The decrease in autoinhaled NO concentration during exercise results from dilution of the continuous nasal release by the increased respiratory gas flow. The individual NO release allows no conclusion about smoking habits.

9 Acute respiratory distress syndrome

Summary The ARDS is characterized by the presence of an acute direct or indirect damage to the lungs followed within 24–72 hours by respiratory distress, arterial hypoxaemia, reduced pulmonary compliance and diffuse bilateral infiltrates visible on chest X-ray. The incidence is low, i.e. between 3 and 10 cases per 100 000 population, but the syndrome has a high mortality of about 50–80%. Within the last years, a trend towards higher survival rates has been observed. Ventilation and other adjunctive strategies in ARDS have changed from the conventional approach aiming at normalization of physiological ventilatory parameters to an elaborated approach that attempts to protect the ventilated lung, prevent oxygen toxicity, recruit the infiltrated, atelectatic and consolidated lung, and reduce the anatomical and alveolar dead space. This new approach consists of different forms of pressure-controlled mechanical ventilation with PEEP and permissive hypercapnia, body position changes, reduction of pulmonary oedema and inhalation of NO. Should these procedures fail to improve impaired gas exchange, extracorporeal respiratory support is an additional therapeutic option. Clinical algorithms that include these therapeutic measures may help to put this new approach into clinical practice. Introduction of such an algorithm into our intensive care practice has been followed by a 77% survival rate in severe ARDS.

DEFINITION, PATHOPHYSIOLOGIE UND EPIDEMIOLOGIE DES AKUTEN LUNGENVERSAGENS

Summary The American-European Consensus Conference recently recommended the following criteria for diagnosis of ARDS: (1) acute onset; (2) PaO2/FiO2≤200 mmHg regardless of PEEP level; (3) bilateral infiltrates seen on frontal chest radiograph; (4) PCWP ≤ 18 mmHg when measured or no clinical evidence of left atrial hypertension. Pathophysiologically, ARDS is characterized by pulmonary edema owing to injury of the capillary-alveolar membranes and increased pulmonary artery pressure. It is further distinguished by severe hypoxemia unresponsive to the usual methods of support for respiratory failure. Hypoxemia is caused by intrapulmonary right-to-left shunting due to to persistent perfusion of non-ventilated alveoli. Another characteristic feature in ARDS is the low thoracopulmonary compliance. Latest studies suggest that the incidence of the syndrome is in the range of 3–10 cases / 100,000 inhabitants / year. Mortality rates are a major concern: old and new reports continue to report mortality rates of 50–60%.Zusammenfassung Die “American-European Consensus Conference” empfahl kürzlich folgende Kriterien zur Diagnose des ARDS: (1) akutes Auftreten; (2) PaO2/FiO2≤200 mmHg unabhängig vom verwendeten PEEP; (3) bilaterale Infiltrationen auf der a.p.-Thoraxröntgenaufnahme; (4) PCWP≤18 mmHg, oder klinischer Ausschluß einer linksatrialen Hypertension. Pathophysiologisch ist das ARDS gekennzeichnet durch das nichtkardiogene Lungenödem als Folge der erhöhten Durchlässigkeit der kapillar-alveolären Membranen und des erhöhten pulmonalarteriellen Drucks. Charakteristisch ist weiterhin die schwere Hypoxämie, die durch den großen intrapulmonalen Rechts-links-Shunt – als Ausdruck der Perfusion nichtventilierter Lungenareale – verursacht wird. Weiterhin ist die thorakopulmonale Compliance deutlich herabgesetzt. Mit einer Inzidenz von 3–10 Fällen / 100.000 Einwohner / Jahr ist das ARDS eine eher seltene Erkrankung, die jedoch auch heute noch mit einer Letalität von 50–60% belastet ist.