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Biomedical subjects

D Pappert

Publications and source records attributed to D Pappert.

At least 37 records · Page 2Linked to original sources

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

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.

Acute Disease↗

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

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 intra-arterial blood gas monitoring in patients suffering from severe acute respiratory distress syndrome. In 10 patients continuous intra-arterial blood gas monitoring based on fluorescent optodes technique was performed. At 4 h intervals, arterial blood samples for in vitro blood gas analyses were drawn, stored in ice, and analysed within 3 min. Evaluation of data retrieved from the continuous intra-arterial blood gas monitoring and in vitro blood gas analysis was based on 596 data points using 10 catheters. Average length of insertion was 281 +/- 215 h, max. lengths of stay was 750 h. Arterial blood gas data obtained in vivo were compared to the mean of in vivo and in vitro arterial blood gases. Inter-catheter bias, expressed as percent difference between continuous intra-arterial blood gas and mean in vitro blood gas analysis was 0.19 +/- 0.23% for pH. 1.1 +/- 5.2% for PaCO2 and 1.6 +/- 5.7% for PaO2. No significant gas partial pressure dependent change in precision was demonstrable. There was no significant time dependent drift in sensor precision over the study period. No negative side-effects related to IABG monitoring were observed. We conclude that long-term use of this new device is possible in patients and represents a reliable alternative to conventional in vitro arterial blood gas analysis, when continuous monitoring of blood gases and/or acid-base balance is critical.

Acid-Base Equilibrium↗

Fractal analysis of surfactant deposition in rabbit lungs.

The effect of exogenous surfactant in the treatment of acute lung injury may depend on homogeneity of distribution of the material delivered. Analyses of distribution rely on sectioning the lung, determining surfactant concentration for each piece, and describing the variation in that value. Results of such analyses are influenced by how finely the lung is sectioned. We have reanalyzed data from prior experiments to determine whether the distribution of administered surfactant is fractal, that is, is independent of the scale of measurement. Lungs from animals receiving surfactant radiolabeled with [3H]dipalmitoylphosphatidylcholine were cut into 108 pieces, and the normalized radioactivity in each piece was determined. Sectioning of the lungs into different numbers of pieces (n = 2, 6, 12, 18, 36, 54, or 108) was simulated, and corresponding radioactivity contents were calculated. The coefficient of variation (CV) of these normalized values was then calculated for each scale of measurement (expressed as relative piece volume), and ln(CV) was plotted as a function of the logarithm of relative piece volume. These relationships were linear (average correlation coefficient = 0.96) for all animals, consistent with CV being a fractal property. We conclude that the intrapulmonary distribution of surfactant may be fractal and is therefore a property of the lung. This study demonstrates the utility of fractal analysis in describing the pulmonary distribution of substances introduced via the airway.

Algorithms↗

Influence of mixed venous PO2 and inspired O2 fraction on intrapulmonary shunt in patients with severe ARDS.

In 12 patients undergoing extracorporeal membrane oxygenation for treatment of severe acute respiratory distress syndrome (ARDS), we examined the effects of independent variations in mixed venous oxygen tension (PvO2) and inspired oxygen fraction (FIO2) on the distribution of ventilation and perfusion as assessed by the multiple inert gas elimination technique. Reducing the oxygen concentration of the constant gas stream through the membrane lungs allowed us to decrease the PvO2 by approximately 20 Torr independently of variations in cardiac output and FIO2 as well as to augment FIO2 without influencing PvO2. The interventions did not induce any change in heart rate or systemic or pulmonary hemodynamics. In general, neither during mechanical ventilation at FIO2 of 0.6 nor during mechanical ventilation at FIO2 of 1.0 did the reduced PvO2 cause variations in the distribution of pulmonary blood flow in our patients with severe ARDS. Nevertheless, in individual patients, decreasing PvO2 or ventilation at FIO2 of 1.0 was associated with changes in intrapulmonary shunt. Therefore, we conclude that it is not possible to predict the influence of such interventions in pulmonary gas exchange in the individual patient suffering from ARDS. Differences in the regulation of the local distribution of blood flow caused by the disease itself might explain this phenomenon.

Acute Disease↗

Efficacy of inhaled nitric oxide in patients with severe ARDS.

STUDY OBJECTIVE: To investigate the initial and long-term effect of nitric oxide (NO) inhalation in patients with severe acute respiratory distress syndrome (ARDS). DESIGN: Retrospective, clinical study. SETTING: University surgical ICU. PATIENTS: Eighty-seven patients with severe ARDS. INTERVENTIONS AND MEASUREMENTS: Thirty of 87 patients with ARDS inhaled low concentrations of NO for more than 48 h in addition to the standard treatment. Initial and long-term effects of NO inhalation on hemodynamics, gas exchange, and methemoglobin formation were determined. Survival of patients treated with inhaled NO was compared with survival in similar patients without NO inhalation. RESULTS: In 83% of the patients, NO increased the ratio of arterial PO2 to the fraction of inspired O2 (PaO2/FIO2) by > or = 10 mm Hg; in 87%, NO reduced venous admixture (QVA/QT) by > or = 10%, and in 63%, NO decreased mean pulmonary artery pressure (PAP) by > or = 3 mm Hg. Daily short interruption of continuous inhalation of NO for a duration of 17 +/- 2.4 days was consistently associated with a decrease in PaO2/FIO2 by 81 +/- 4 mm Hg (p < 0.001). QVA/QT increased by 8.3 +/- 0.4% (p < 0.001) and PAP by 5.3 +/- 0.3 mm Hg (p < 0.001). Over time, we observed neither tachyphylaxis nor a more pronounced effect of inhaled NO. Methemoglobin increased from 0.74 +/- 0.56% to 0.98 +/- 0.02% (p < 0.001). Survival rates in patients treated with NO did not differ from survival rates in patients not treated with NO. CONCLUSION: Beneficial effects of NO inhalation can be observed in most patients with severe ARDS; in some cases, however, it may fail to improve pulmonary gas exchange or to reduce pulmonary hypertension without obvious explanation. To demonstrate a possible increase in survival associated with NO inhalation, large randomized prospective trials are required.

Adolescent↗

Recent advances in the treatment of ARDS.

Despite more than 25 years of extensive research the mortality of ARDS patients remains high. Besides the often deleterious course of the underlying disease, another reason for this high mortality lies in the aggressive ventilatory regimen which is required to maintain arterial blood gases in a more or less normal range. Therapeutic methods which are used to reduce iatrogenic damage to the lungs are pressure controlled ventilation with permissive hypercapnia, differential lung ventilation, positioning therapy, dehydration, and extracorporeal gas exchange with membrane lungs. Nevertheless, many of these patients still die following hypoxaemia or multiple organ failure. Therefore, the need remains to develop new therapeutic strategies and to investigate their influence on the morbidity and mortality of this life-threatening disease. First experiences with nitric oxide (NO) inhalation, intravenous application of antioxidants, intratracheal instillation of surfactant, tracheal gas insufflation and combined fluid/gas ventilation with perfluorocarbon are presented. All these new methods have proved their efficacy, at least in animal studies, however, they should still be regarded as experimental.

Animals↗

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.

Adolescent↗

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

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.

Acute Disease↗

[Therapy of ARDS. 1. Current therapeutic strategy including extracorporeal gas exchange].

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.

Extracorporeal Membrane Oxygenation↗

[Therapy of ARDS. 2. New management methods--first clinical experiences].

Conventional treatment of the adult respiratory distress syndrome (ARDS) includes pressure-limited ventilation, permissive hypercapnia, posture changes, aggressive dehydration, selective lung ventilation, and extracorporeal gas exchange. New strategies such as nitric oxide inhalation, the implantation of an intravenous membrane oxygenator (IVOX), and surfactant replacement are currently under evaluation. Nitric oxide (NO) is an important endothelium-derived relaxing factor that is rapidly inactivated by binding to haemoglobin. Inhaling this substance has been shown to induce selective vasodilatation of ventilated lung regions. Thus, inhaled NO reduces pulmonary hypertension, increases right heart ejection fraction, and improves arterial oxygenation by redistributing blood flow away from areas with intrapulmonary shunts to areas with a normal ventilation/perfusion ratio. Dose-response analysis has revealed that effective doses for improvement of oxygenation are lower than for reduction of mean pulmonary artery pressure. The use of a miniaturised membrane lung, IVOX, for intracaval oxygen and carbon dioxide exchange is a new approach to augment gas exchange. The IVOX is inserted via an introducer into the femoral vein and is designed for placement in the full length of the vena cava. Initial experiences with this device show that the currently used prototype provides a maximum of one-third of basal gas exchange. Therefore, a more efficient device will be needed to significantly reduce high inspired oxygen concentrations and airway pressures. Moreover, there exists evidence that IVOX causes caval obstruction. Lung surfactant recovered in BAL from patients with ARDS demonstrates that fractional contents of phosphatidylcholine and phosphatidylglycerol are reduced, and that the total concentration of apoproteins is decreased. Furthermore, the surfactant surface tension-lowering activity is abnormal. Thus, administration of exogenous surfactant may have therapeutic benefits. However, the optimal surfactant preparation, the optimal amount required to restore lung surfactant activity, and the optimal method to deliver it to patients with ARDS are unknown and currently under evaluation.

Adult↗

Acute effects of a single dose of porcine surfactant on patients with the adult respiratory distress syndrome.

In an attempt to restore functional surfactant to the lungs of patients with the adult respiratory distress syndrome (ARDS), we have treated six patients within the first 2 days of the onset of ARDS with a single dose of hydrophobic components of porcine surfactant. Surfactant (4 g in 50 ml) delivered via a bronchoscope in aliquots to each of the lobar bronchi was well tolerated and caused a modest transient improvement in gas exchange. No significant changes in chest radiograph or lung compliance were detected. Analysis of bronchoalveolar lavage (BAL) fluid showed no change in albumin, alpha-1-proteinase inhibitor specific activity, or cell count. Bronchoalveolar lavage phospholipid concentrations were elevated 3 h after surfactant administration relative to preadministration levels and fell by 24 h. In addition, in two patients we found reduced inhibition of surfactant function in BAL after surfactant replacement. These observations suggest a role for surfactant replacement in the treatment of patients with ARDS and support the need for continuing investigation.

Adult↗

Influence of positioning on ventilation-perfusion relationships in severe adult respiratory distress syndrome.

In 12 patients with severe adult respiratory distress syndrome (ARDS), pulmonary gas exchange and hemodynamics were evaluated before, during, and after a 2-h period of pressure-controlled mechanical ventilation with the patient in the prone position. Ventilation-perfusion relationships (VA/Q) were assessed by a multiple inert gas elimination technique. Pressure-controlled mechanical ventilation in the prone position resulted in an overall increase (p < or = 0.05) of arterial oxygenation after 120 min (98.4 +/- 50.3 to 146.2 +/- 94.9 mm Hg). Whereas eight patients revealed an improvement of PaO2 of more than 10 mm Hg after 30 min in the prone position (responders), four patients reacted to positional changes with a deterioration of arterial oxygenation (nonresponders). Data about the continuous distribution of ventilation-perfusion ratios revealed that in the responder group positioning caused a decrease of shunt perfusion of 11 +/- 5% and a concomitant increase of normal VA/Q by 12 +/- 4% after 30 min. There was no change demonstrable within low VA/Q areas. Returning the patient to the supine position reversed the improvement in gas exchange. The nonresponder group did not show any significant alteration in the distribution of VA/Q during the study. We concluded that improvement of oxygenation during pressure-controlled mechanical ventilation in the prone position is due to a shift of blood flow away from shunt regions, thus increasing areas with normal VA/Q. This redistribution of blood flow is most likely caused by a recruitment of previously ateletatic but nondiseased areas induced by altered gravitational forces.

Adolescent↗

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

OBJECTIVE: To 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. DESIGN: Prospective, clinical study. SETTING: Anesthesiological ICU in a university hospital. PATIENTS: 3 consecutive patients with severe ARDS according to clinical and radiological signs. INTERVENTIONS: Pressure-controlled ventilation with positive end-expiratory 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 RESULTS: Initial 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 (Qva/Qt) 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. CONCLUSIONS: The 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.

Administration, Inhalation↗

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

Inhalation of nitric oxide (NO), an endogenous 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.

Administration, Inhalation↗

[Experiences with simultaneous exploration of the bile ducts in surgical therapy of gallstone ileus].

During the last 16 years, 14 patients with a gallstone ileus were treated at our institution. In 11 cases we performed in addition to the enterolithotomy, a cholecystectomy and a resection of the fistula as one-stage repair. Despite the high average age (74.3 years) and the presence of various other serious morbidity in our patient population, we only observed a hospital mortality of 7.1%. Serious postoperative complications, such as sepsis and/or shock were not observed. Utilizing today's advanced anesthesia and proper intensive-care therapy, as well as early operative intervention and safe surgical technique, we believe that enterolithotomy with cholecystectomy and fistula resection as one-stage operation, should primarily be considered before performing enterolithotomy alone.

Aged↗