Dirk Pappert

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.

Autoinhalation of nitric oxide after endogenous synthesis in nasopharynx.

Exogenous nitric oxide (NO) reduces pulmonary vascular resistance after low-dose inhalation in patients. To estimate endogenous NO synthesis in the upper respiratory tract, we measured inhaled and exhaled NO in volunteers and patients during spontaneous or controlled ventilation, respectively. 20.3 nmol per min NO was synthesised in the nasopharynx of non-smoking volunteers, leading to autoinhalation of 0.07-0.13 NO parts per million during inspiration; smokers had reduced NO synthesis. In volunteers, 50-70% of the NO was resorbed by the lungs; ventilated patients were deprived of NO autoinhalation. Bacteria in the nose may take part in endogenous NO synthesis.

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 admixture

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

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

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.

Effect of N-nitroso-N-methylurethane on gas exchange, lung compliance, and surfactant function of rabbits.

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.

Continuous monitoring of blood gases during hypercapnia in a patient with severe acute lung failure

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.

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

The purposes of this report are to describe percutaneous osteoplasty as a highly effective minimally invasive procedure to treat painful malignant bone lesions of the pelvis, ilium, and femur and to discuss the relevant literature. Five patients with histologically proven metastases to the pelvis, ilium, or femur were treated by percutaneous injection of liquid bone cement as an attempt to control severe bone pain. After percutaneous osteoplasty, all five patients experienced immediate and substantial pain relief and did not require pain medication for the duration of follow-up. No clinically significant complications occurred. Whereas percutaneous osteoplasty of the spine (vertebroplasty) is well-described and widely accepted to treat pain caused by benign or malignant vertebral body diseases, osteoplasty of bones outside the spine is less known. The immediate good clinical results observed in our small patient group should encourage more widespread application of this palliative treatment.