Klaus Slama

Inhaled Nitric Oxide for the Adult Respiratory Distress Syndrome

BACKGROUND The adult respiratory distress syndrome is characterized by pulmonary hypertension and right-to-left shunting of venous blood. We investigated whether inhaling nitric oxide gas would cause selective vasodilation of ventilated lung regions, thereby reducing pulmonary hypertension and improving gas exchange. METHODS Nine of 10 consecutive patients with severe adult respiratory distress syndrome inhaled nitric oxide in two concentrations for 40 minutes each. Hemodynamic variables, gas exchange, and ventilation-perfusion distributions were measured by means of multiple inert-gas-elimination techniques during nitric oxide inhalation; the results were compared with those obtained during intravenous infusion of prostacyclin. Seven patients were treated with continuous inhalation of nitric oxide in a concentration of 5 to 20 parts per million (ppm) for 3 to 53 days. RESULTS Inhalation of nitric oxide in a concentration of 18 ppm reduced the mean (+/- SE) pulmonary-artery pressure from 37 +/- 3 mm Hg to 30 +/- 2 mm Hg (P = 0.008) and decreased intrapulmonary shunting from 36 +/- 5 percent to 31 +/- 5 percent (P = 0.028). The ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2), an index of the efficiency of arterial oxygenation, increased during nitric oxide administration from 152 +/- 15 mm Hg to 199 +/- 23 mm Hg (P = 0.008), although the mean arterial pressure and cardiac output were unchanged. Infusion of prostacyclin reduced pulmonary-artery pressure but increased intrapulmonary shunting and reduced the PaO2/FiO2 and systemic arterial pressure. Continuous nitric oxide inhalation consistently lowered the pulmonary-artery pressure and augmented the PaO2/FiO2 for 3 to 53 days. CONCLUSIONS Inhalation of nitric oxide by patients with severe adult respiratory distress syndrome reduces the pulmonary-artery pressure and increases arterial oxygenation by improving the matching of ventilation with perfusion, without producing systemic vasodilation. Randomized, blinded trials will be required to determine whether inhaled nitric oxide will improve outcome.

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.

Effects of inhaled nitric oxide on right ventricular function in severe acute respiratory distress syndrome

ObjectiveTo compare the effects of inhaled nitric oxide (NO) and an infusion of prostacyclin (PGI2) on right ventricular function in patients with severe acute respiratory distress syndrome (ARDS).DesignRandomized prospective short-term study.Setting: Post-surgical ICU in an university hospital.Patients10 patients with severe ARDS referred to our hospital for intensive care.InterventionsIn random sequence the patients inhaled NO at a concentration of 18 parts per million (ppm) followed by 36 ppm, and received an intravenous infusion of PGI2 (4 ng·kg−1·min−1).Measurement and resultsInhalation of 18 ppm NO reduced the means (±SE) pulmonary artery pressure (PAP) from 33±2 to 28±1 mmHg (p=0.008), increased right ventricular ejection fraction (RVEF), as assessed by thermodilution technique, from 28±2 to 32±2% (p=0.005), decreased right ventricular end-diastolic volume index from 114±6 to 103±8 ml·m−2 (p=0.005) and right ventricular end-systolic volume index from 82±4 to 70±5 ml·m−2 (p=0.009). Mean arterial pressure (MAP) and cardiac index (CI) did not change significantly. The effects of 36 ppm NO were not different from the effects of 18 ppm NO. Infusion of PGI2 reduced PAP from 34±2 to 30±2 mmHg (p=0.02), increased RVEF from 29±2 to 32±2% (p=0.02). Right ventricular end-diastolic and end-systolic volume indices did not change significantly. MAP decreased from 80±4 to 70±5 mmHg (p=0.03), and CI increased from 4.0±0.5 to 4.5±0.5 l·min−1·m−2 (p=0.02).ConclusionsUsing a new approach to selective pulmonary vasodilation by inhalation of NO, we demonstrate in this groups of ARDS patients that an increase in RVEF is not necessarily associated with a rise in CI. The increase in CI during PGI2 infusion is probably related to the systemic effect of this substance.

A new method for PO.1 measurement using standard respiratory equipment

The airway occlusion pressure, P0.1, is an index for the neuro-muscular activation of the respiratory system. It has been shown to be a very useful indicator for the ability of patients receiving ventilatory support to be weaned from mechanical ventilation. Since the standard measurement technically complex, it is not widely available for clinical purposes. For that reason a P0.1 measurement technique was developed as an integrated function in a standard respirator (Evita, Dräger, Lübeck, Germany). This technique is easy to use and does not need any further equipment. We validated this new technique by comparing it to standard P0.1 measurements in a mechanical lung model as well as in ventilated patients. In the lung model we found a correlation between the Evita measurement and standard measurements ofr=0.99. In 6 ventilated patients the correlation wasr=0.78. Since the Evita P0.1 and the standard measurement had to be performed during two different breaths, this little poorer correlation in patients may be due to a significant breath-by-breath variability in P0.1. Comparing the Evita P0.1 and the standard measurement within one breath resulted in a clearly better correlation (r=0.89). We conclude that this new measurement technique provides and easy and accurate P0.1 measurement using standard respiratory equipment when tested in a lung model. In patient measurements the method is less precise, which is probably due to the variable waveforms of the inspiratory driving pressure seen in patients, for example when intrinsic PEEP is present. However, the new method makes the P0.1 measurement as a “bed-side” method clinically available, although the values should be interpreted cautiously.

Bacterial and fungal colonization and infections using oral selective bowel decontamination in orthotopic liver transplantations

Bacterial and fungal infections are a major cause of morbidity and mortality after orthotopic liver transplantation. In the immunocompromised host, infections are thought to arise from the gut, which is almost always colonized with potential pathogens. Using oral selective bowel decontamination (SBD), potential pathogens can be eradicated from the gut and infections prevented. In this catamnestic study we have reviewed gastrointestinal colonization, bacterial and fungal infections, and bacterial resistance to standard antibiotics in our first 206 liver transplant patients while under SBD. With few exceptions, gram-negatives were eradicated from the gastrointestinal tract and secondary colonization was inhibited. In spite of unsatisfactory elimination of Candida, probably because nystatin doses were too low, Candida infections were rare (n=4) and none was fatal. One and two-year survival rates were 93% and 92%, respectively. The bacterial and fungal infection rate was 27.8% with an infection-related mortality of 1.95%. Infections with aerobic grampositive bacteria prevailed and only 11 gram-negative and 11 fungal infections occurred; among the latter, Aspergillus and Mucor were the most serious and responsible for three of the six deaths in this series. With regard to the development of resistance, we found an increasing number of enterococci and coagulase-negative staphylococci resistant to ciprofloxacin and imipenem, respectively, but unlikely as a consequence of SBD.

Therapy of the acute respiratory distress syndrome. Part I: Current therapeutic strategy including extracorporeal gas exchange

Zusammenfassung. Die Therapie des schweren akuten Lungenversagens des Erwachsenen (acute respiratory distress syndrome=ARDS) umfaßt bis heute vorwiegend unterstützende, auf eine Normalisierung des Gasaustauschs ausgerichtete Maßnahmen. Druckbegrenzte Beatmung mit positiv endexspiratorischem Druck in Verbindung mit permissiver Hyperkapnie, seitendifferenter Beatmung, Seiten- und Bauchlagerung und Dehydratation zielen auf eine Reduktion der zur Aufrechterhaltung annähernd normaler Blutgase notwendigen hohen Atemwegsspitzendrücke und inspiratorischen Sauerstoffkonzentrationen und somit auf eine Abschwächung iatrogener Faktoren, die wesentlich zur Progression der Lungenschädigung beitragen können. Extrakorporale Verfahren zur Unterstützung des Gasaustauschs sollten dann in Betracht gezogen werden, wenn mit diesen etablierten Behandlungsregimen keine Besserung des pulmonalen Gasaustauschs erzielt werden kann und wenn die Prognose der Grunderkrankung als günstig anzusehen ist. Mit diesem Therapiekonzept konnte im eigenen Patientengut eine Überlebensrate von 75% (67 von 89 Patienten) erreicht werden.Abstract. Recent studies and reviews continue to report a high mortality associated with the acute respiratory distress syndrome (ARDS), which involves a severe inflammatory reaction within the whole lung that is frequently associated with multiple-organ failure. Important factors contributing to the poor results in severe ARDS are the aggressive procedures required to maintain sufficient arterial oxygenation, such as mechanical ventilation with high inspiratory pressures and high inspired oxygen concentrations (FiO2) which themselves contribute to the progression of the disease. As no specific therapy that reduces or prevents the general inflammatory reaction is known, current therapy is limited to procedures that minimize peak inspiratory pressures and FiO2. Therefore, pressure- and volume-limited ventilation modes with positive end-expiratory pressure, controlled hypercapnia, differential lung ventilation when appropriate, positioning (particularly prone), and aggressive dehydration are used. Should these procedures fail to improve arterial gas exchange, the patients may be additionally treated by veno-venous extracorporeal gas exchange. To reduce the risk of severe haemorrhagic complications due to high levels of systemic heparinization, systems internally coated with covalently bound heparin, which allow a lower level of systemic anticoagulation, should be used. From April 1989 to August 1993, 89 patients were transferred to our intensive care unit for treatment of severe ARDS; 52 were treated by combining the described conventional methods without artificial gas exchange (survival rate 88%) and 37 additionally underwent artificial gas exchange (survival rate 57%). The overall survival rate was 75%. On the basis of these experiences, we conclude that this step-by-step approach may improve survival in patients with severe ARDS.