Herwig Gerlach

Time‐course and dose‐response of nitric oxide inhalation for systemic oxygenation and pulmonary hypertension in patients with adult respiratory distress syndrome

Abstract. Inhalation of nitric oxide (NO), an endoge‐neous vasodilator, was recently described to reduce pulmonary vascular resistance, and to improve arterial oxygenation by selective vasodilation of ventilated areas in patients with adult respiratory distress syndrome (ARDS). We describe the time‐course and dose‐response of initial short‐term NO inhalation in 12 patients with ARDS. Enhanced oxygenation was achieved within 1–2 min after starting NO inhalation; after inhalation, baseline conditions were re‐achieved within 5–8 min. Effective doses for improvement of oxygenation [baseline: PaO2= 10.2±2.5 KPa (76.4±18.7 mmHg)] were low: ED50 was about 100 ppb—a concentration similar to the atmosphere. NO doses of more than 10 ppm [10 ppm NO: PaO2=17.3 ± 3.3 KPa (129.4 ± 25.1 mmHg)] re‐worsen the arterial oxygenation. The ED50 for reduction of mean pulmonary artery pressure was 2–3 ppm. This indicates that inhalation of NO for improvement of oxygenation in severe ARDS should be performed using lower doses, with lower risk of toxic side effects.

Long-term inhalation with evaluated low doses of nitric oxide for selective improvement of oxygenation in patients with adult respiratory distress syndrome

AbstractObjectiveTo evaluate the lowest dose of inhaled nitric oxide (NO) in patients with adult respiratory distress syndrome (ARDS), which is able to improve arterial oxygenation more than 30% compared to baseline data.DesignProspective, clinical study.SettingAnesthesiological ICU in a university hospital.Patients3 consecutive patients with severe ARDS according to clinical and radiological signs.InterventionsPressure-controlled ventilation with positive endexpiratory pressure of 8–12 cm H2O. Inhalation of NO was performed with a blender system and a Servo 300 ventilator. The lowest effective NO dose was defined by titrating the inspiratory NO dose until reaching a 30% improvement of PaO2/FiO2. This dose was used for the following continuous long-term NO inhalation; controls of efficacy by investigation of hemodynamics and blood gas exchange were performed initially and 2 times per patient after intervals of 3–5 days.Measurements and resultsInitial NO concentrations were found to be effective at 60, 100, and 230 parts per billion (ppb). In all measurements, arterial oxygenation was found to be elevated by NO inhalation with the initially evaluated dose compared to baseline data; in parallel, the venous admixturen

Preliminary evaluation of a new continuous intra-arterial blood gas monitoring device.

left( {{{dot Q_{va} } mathord{left/ {vphantom {{dot Q_{va} } {dot Q_t }}} right. kern-nulldelimiterspace} {dot Q_t }}} right)

Extracorporeal membrane oxygenation with heparin-coated systems in a 13-month-old infant with acute hypoxic respiratory failure after correction of tetralogy of Fallot.

n was reduced. The O2 delivery increased, although O2 consumption and hemodynamics did not change. In 1 patient, interruption of NO inhalation caused remarkable increase of pulmonary resistance.ConclusionsThe improvement of oxygenation by NO inhalation in ARDS does not require reduction of pulmonary resistance and can be performed using low doses in the ppb range, which has to be considered as probably non-toxic.

Therapy of the acute respiratory distress syndrome. Part 2: Initial clinical experience with new therapeutic methods

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.

Efficacy of Inhaled Nitric Oxide in Patients With Severe ARDS

Continuous intra‐arterial blood gas monitoring is a new technique, possibly offering therapeutic advantages through improved monitoring in patients prone to hypoxaemia, hypercapnia and/or respiratory acidosis. Therefore, we studied the clinical applicability, reliability, precision and side effect of long‐term continuous intraarterial blood gas monitoring in patients suffering from severe acute respiratory distress syndrome.

Epidemiology of sepsis in Germany: results from a national prospective multicenter study. Intensive Care Med

We report about our first experiences with a new device for continuous intra-arterial monitoring of blood gases in a patient with severe acute respiratory failure. This device facilitated continuous monitoring of PaO2, PaCO2 and pH while weaning the patient from extracorporeal membrane oxygenation (ECMO). Although sufficient oxygenation at FIO2 0.45 could be achieved after disconnection from ECMO, carbon dioxide elimination remained inadequate and resulted in severe respiratory acidosis. Within six hours, PaCO2 increased to 95 mmHg. Continuous monitoring of pH and PaCO2 helped to monitor CO2 retention and assisted the decision making process for reinstitution of ECMO.

A double-blind, randomized, placebo-controlled, cross-over study

Hemorrhagic disorders due to systemic heparinization are frequent during extracorporeal lung support (veno-venous extracorporeal membrane oxygenation: vv-ECMO). The development of heparin-coated systems has reduced the need for high-dose heparinization. Whereas the use of these heparin-coated membrane lungs and tubings has been described in former studies in adults, only few reports exist in children. This case report describes the application of a heparin-coated extracorporeal system for long-term vv-ECMO in a 13-month-old infant suffering from acute hypoxic respiratory failure after correction of tetralogy of Fallot. Only moderately elevated levels of activated clotting time (ACT, 120-160 s) and activated partial thromboplastin time (aPTT, 40-60 s) were necessary to avoid thrombotic events in the extracorporeal system. Thoracotomies were performed twice without bleeding complications by discontinuation of the systemic heparinization. We conclude that the use of heparin-coated membrane lungs in infants may improve the safety of extracorporeal lung support and permits surgical intervention without major risk of bleeding.