Andreas Reske

Use of dynamic compliance for open lung positive end-expiratory pressure titration in an experimental study

Objective: We tested whether the continuous monitoring of dynamic compliance could become a useful bedside tool for detecting the beginning of collapse of a fully recruited lung. Design: Prospective laboratory animal investigation. Setting: Clinical physiology research laboratory, University of Uppsala, Sweden. Subjects: Eight pigs submitted to repeated lung lavages. Interventions: Lung recruitment maneuver, the effect of which was confirmed by predefined oxygenation, lung mechanics, and computed tomography scan criteria, was followed by a positive end‐expiratory pressure (PEEP) reduction trial in a volume control mode with a tidal volume of 6 mL/kg. Every 10 mins, PEEP was reduced in steps of 2 cm H2O starting from 24 cm H2O. During PEEP reduction, lung collapse was defined by the maximum dynamic compliance value after which a first measurable decrease occurred. Open lung PEEP according to dynamic compliance was then defined as the level of PEEP before the point of collapse. This value was compared with oxygenation (Pao2) and CT scans. Measurements and Main Results: Pao2 and dynamic compliance were monitored continuously, whereas computed tomography scans were obtained at the end of each pressure step. Collapse defined by dynamic compliance occurred at a PEEP of 14 cm H2O. This level coincided with the oxygenation‐based collapse point when also shunt started to increase and occurred one step before the percentage of nonaerated tissue on the computed tomography exceeded 5%. Open lung PEEP was thus at 16 cm H2O, the level at which oxygenation and computed tomography scan confirmed a fully open, not yet collapsed lung condition. Conclusions: In this experimental model, the continuous monitoring of dynamic compliance identified the beginning of collapse after lung recruitment. These findings were confirmed by oxygenation and computed tomography scans. This method might become a valuable bedside tool for identifying the level of PEEP that prevents end‐expiratory collapse.

Alveolar recruitment in combination with sufficient positive end-expiratory pressure increases oxygenation and lung aeration in patients with severe chest trauma.

ObjectiveInvestigation of oxygenation and lung aeration during mechanical ventilation according to the open lung concept in patients with acute lung injury or acute respiratory distress syndrome. DesignRetrospective analysis. SettingSurgical intensive care unit of a university hospital. PatientsWe retrospectively identified 17 patients with acute lung injury/acute respiratory distress syndrome due to pulmonary contusion who had thoracic helical computed tomography scans before and after ventilation with the open lung concept. InterventionsBaseline ventilation consisted of low tidal volumes (≤6 mL/kg) and positive end-expiratory pressure (PEEP; 5–17 cm H2O). We briefly applied high inspiratory pressures for opening up collapsed alveoli. External PEEP and intrinsic PEEP were combined to keep recruited lung units open. We generated intrinsic PEEP by pressure-cycled high-frequency inverse ratio ventilation (80 min−1, inspiratory/expiratory ratio 2:1) and maintained our ventilatory strategy for 24 hrs. Then, after reducing total PEEP by decreasing respiratory rate, Pao2/Fio2 ratio was reevaluated. If it remained >300 mm Hg, weaning was started. If not, previous ventilator settings were resumed for another 24 hrs after recruiting the lungs once again. Measurements and Main ResultsPhysiologic variables and ventilator settings were obtained from routine charts. Data from computed tomography before and after the open lung concept were analyzed for volumetric quantification of lung aeration and collapse. All results are presented as median and range. During baseline ventilation, PEEP was 10 (range, 5–17) cm H2O and after recruitment 21 (range, 18–26) cm H2O. Opening pressures were 65 (range, 50–80) cm H2O. After recruitment, Pao2/Fio2 ratio was higher in all patients. Total lung volume increased from 2915 (range, 1952–4941) to 4247 (range, 2285–6355) mL and normally aerated volume from 1742 (range, 774–2941) to 2971 (range, 1270–5232) mL. Atelectasis decreased significantly from 604 (range, 147–1538) to 106 (range, 0–736) mL. Hyperinflation increased significantly from 5 (range, 0–188) to 62 (range, 1–424) mL, whereas poor aeration did not change substantially from 649 (range, 302–1292) to 757 (range, 350–1613) mL. No hemodynamic problems occurred. ConclusionsLung recruitment increased arterial oxygenation, normally aerated lung volume, and total lung volume while decreasing the amount of collapsed tissue. These results indicate that the open lung concept is a reasonable mode of ventilation for patients with severe chest trauma.

Complications and Adverse Effects Associated with Continuous Peripheral Nerve Blocks in Orthopedic Patients

BACKGROUND:The increasing popularity of continuous peripheral nerve blocks (CPNBs) warrants further study of their adverse effects and complications. METHODS:Anterior sciatic, femoral, and interscalene brachial plexus CPNBs were performed preoperatively using standardized catheter techniques in orthopedic patients prior to general or spinal anesthesia. Complications and adverse effects related to CPNBs were prospectively evaluated. RESULTS:We analyzed 1398 CPNBs in 849 consecutive patients (mean age 65 ± 13 yr) between 2002 and 2004. Two-hundred-twenty-one patients received interscalene, 628 patients femoral, and 549 sciatic CPNBs, respectively. In all the latter patients, we performed both femoral and sciatic CPNBs. Overall, there were 9 cases of local inflammation at the insertion site (0.6%), and 3 local infections (pustule) (0.2%, all femoral CPNBs). In one patient undergoing a femoral technique, a retroperitoneal hematoma led to compression injury of the femoral nerve. Complete denervation of the quadriceps femoris muscle was confirmed by electroneuromyography. No other major neurological complications were noted. There was one case of methemoglobinemia associated with an interscalene CPNB. Vascular puncture occurred in approximately 6% of patients undergoing femoral and sciatic CPNBs. Catheter rupture was noted in one patient. CONCLUSIONS:Our results add to the evidence that major complications from CPNBs are rare. However, minor adverse effects associated with CPNBs may be more common.

Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules.

Cold thyroid nodules (CTNs) are characterized by a reduced iodide uptake in comparison to normal thyroid tissue. The sodium iodide symporter (NIS) is the first step in thyroid hormone synthesis and mediates the active iodide transport in the thyroid cells suggesting that decreased iodide uptake could be a result of changes in NIS expression or molecular defects in the NIS gene. In contrast to previous studies, an intraindividual comparison of NIS mRNA expression in CTNs and their corresponding surrounding tissue was performed using direct detection of NIS mRNA. A significant reduction in NIS mRNA expression was detected in 86% of the 14 investigated CTNs. We hypothesized that human sodium iodide symporter (hNIS) transcriptional failure could be caused by primary molecular NIS gene defects and/or methylation of DNA in the NIS promoter. However, no mutation in the NIS cDNA nor in the NIS promoter region upstream up to-443 bp from the ATG start codon was detected. Therefore, primary molecular NIS gene defects were excluded. However, in 50% of CTNs with reduced NIS mRNA expression, the promoter region was hypermethylated. NIS mRNA expression in these hypermethylated CTNs only reached a maximum of 30% of the corresponding surrounding tissue. Hence, methylation of CpG islands in the NIS promotor could be a regulatory mechanism of NIS transcription in CTNs. Immunoblot revealed absent hNIS protein expression in the total cell membrane fraction in 45% of investigated nodules. In the majority of the remaining CTNs NIS protein expression was decreased in the nodule tissue compared to the corresponding surrounding tissue. For investigating protein expression immunhistochemistry has two advantages. First, the whole nodule area can be investigated, and second, NIS expression can be detected in areas where an immunoblot of a cell membrane fraction is negative. Interestingly, immunhistochemistry revealed higher NIS expression in 50% of CTNs compared to their corresponding surrounding tissues and NIS staining was predominantly intracellular. These data demonstrate that NIS protein expression does not reflect NIS mRNA expression. Therefore, factors that affect targeting of NIS to the plasma membrane are likely to be affected.

The open lung concept. Clinical application in severe thoracic trauma

AbstractIntroduction. The pathomorphological substratum of the pulmonary contusion is a parenchymatous hemorrhage followed by interstitial and alveolar edema, finally resulting in a severe damage of the surfactant system. The pathophysiological consequence is an imbalance between ventilation and perfusion, which causes the clinical finding of hypoxia. Methods. Between December 1997 and December 2000, we treated 32 polytraumatized patients (ISS 43, PTS 32) additionally suffering from severe chest contusion (AIS 5, PTST 14), by ventilation according to the Open Lung Concept (OLC). The initial disturbance of oxygenation was shown by a mean paO2/FIO2-ratio of 134 (96;181) mmHg. The OLC recruits atelectatic lung areas by the application of a defined temporary positive inspiratory pressure (PIP), which is called the “opening pressure”. The recruited lung areas were kept open by high total-PEEP. Results. For the recruitment procedure, a mean PIP of 65 (51;65) mbar was required. Recruited alveoli were kept open by a total-PEEP of 22 (20;23) mbar. The paO2/FIO2-ratio increased significantly (P<0.001) from 134 (96;181) to 522 (433;587) mmHg. After the recruitment procedure, we could reduce PIP and FIO2. In spite of the minimal tidal volumes of 3.5 (3.0;3.9) ml per kg bodyweight by which our patients were ventilated, the levels of oxygenation and normocapnia could be maintained. There were no evidences for side-effects like perfusion impairment. Two patients (6.25%) died of extrapulmonary causes. Conclusion. Ventilation according to the OLC seems to be a highly effective treatment of ventilation-perfusion-impairment following pulmonary contusion. Minimal tidal volumes and the low PIP-levels after the recruitment procedure meet the demands of a lung-protective Low-Tidalvolume-Ventilation.ZusammenfassungHintergrund. Das pathomorphologische Substrat der Lungenkontusion stellen initiale Parenchymeinblutungen, gefolgt von einem interstitiellen und alveolären Ödem mit Surfactant-Schaden dar. Die pathophysiologische Folge ist ein Ventilations-Perfusions-Missverhältnis mit resultierender Hypoxie. Methoden. In einer klinischen Anwendungsbeobachtung haben wir von 12/1997 bis 12/2000 32 polytraumatisierte Patienten (ISS: 43, PTS: 32) mit erheblicher thorakaler Beteiligung (AIS: 5, PTST: 14) und resultierender schwerer Oxygenierungsstörung (paO2/FIO2-Quotient 134 mmHg) entsprechend dem Open Lung Concept (OLC) ventiliert. Es erfolgten die Öffnung der atelektatischen Lungenabschnitte mit einem definierten hohen temporären “Öffnungsdruck” und das “Offenhalten” der rekrutierten Lungenabschnitte mit einem entsprechend hohen PEEP. Ergebnisse. Für das Öffnungsmanöver (ÖM) wurde ein medianer PIP von 65 (51;65) mbar benötigt. Zum Offenhalten der rekrutierten Alveolen war ein medianer Total-PEEP von 22 (20;23) mbar notwendig. Resultierend konnte der Oxygenierungsindex von 134 (96;181) auf 522 (433;587) mmHg signifikant (p<0,001) angehoben werden. Im Verlauf der Behandlung gelang nach dem ÖM die Reduktion von PIP und FIO2. Trotz der Beatmung mit kleinsten Tidalvolumina von 3,5 (3,0;3,9) ml/kg KG gelang sowohl die Aufrechterhaltung des Oxygenierungsniveaus als auch die Gewährleistung einer Normokapnie. Nebenwirkungen hinsichtlich längerfristiger Perfusionsbeeinträchtigungen waren nicht zu verzeichnen. Zwei Patienten (6,25%) verstarben an extrapulmonalen Ursachen. Schlussfolgerung. Das OLC ermöglicht eine suffiziente Behandlung des Ventilations-Perfusions-Missverhältnisses nach Lungenkontusion. Die niedrigen TV- und PIP-Niveaus nach ÖM erfüllten die Ansprüche einer lungenprotektiven Low-Tidalvolume-Ventilation.

Early recovery from post-traumatic acute respiratory distress syndrome.

Background  To present and discuss the rationale and possible benefits of timely alveolar recruitment in early post‐traumatic acute respiratory distress syndrome.

Das Open Lung ConceptKlinische Anwendung beim schweren Thoraxtrauma

AbstractIntroduction. The pathomorphological substratum of the pulmonary contusion is a parenchymatous hemorrhage followed by interstitial and alveolar edema, finally resulting in a severe damage of the surfactant system. The pathophysiological consequence is an imbalance between ventilation and perfusion, which causes the clinical finding of hypoxia. Methods. Between December 1997 and December 2000, we treated 32 polytraumatized patients (ISS 43, PTS 32) additionally suffering from severe chest contusion (AIS 5, PTST 14), by ventilation according to the Open Lung Concept (OLC). The initial disturbance of oxygenation was shown by a mean paO2/FIO2-ratio of 134 (96;181) mmHg. The OLC recruits atelectatic lung areas by the application of a defined temporary positive inspiratory pressure (PIP), which is called the “opening pressure”. The recruited lung areas were kept open by high total-PEEP. Results. For the recruitment procedure, a mean PIP of 65 (51;65) mbar was required. Recruited alveoli were kept open by a total-PEEP of 22 (20;23) mbar. The paO2/FIO2-ratio increased significantly (P<0.001) from 134 (96;181) to 522 (433;587) mmHg. After the recruitment procedure, we could reduce PIP and FIO2. In spite of the minimal tidal volumes of 3.5 (3.0;3.9) ml per kg bodyweight by which our patients were ventilated, the levels of oxygenation and normocapnia could be maintained. There were no evidences for side-effects like perfusion impairment. Two patients (6.25%) died of extrapulmonary causes. Conclusion. Ventilation according to the OLC seems to be a highly effective treatment of ventilation-perfusion-impairment following pulmonary contusion. Minimal tidal volumes and the low PIP-levels after the recruitment procedure meet the demands of a lung-protective Low-Tidalvolume-Ventilation.ZusammenfassungHintergrund. Das pathomorphologische Substrat der Lungenkontusion stellen initiale Parenchymeinblutungen, gefolgt von einem interstitiellen und alveolären Ödem mit Surfactant-Schaden dar. Die pathophysiologische Folge ist ein Ventilations-Perfusions-Missverhältnis mit resultierender Hypoxie. Methoden. In einer klinischen Anwendungsbeobachtung haben wir von 12/1997 bis 12/2000 32 polytraumatisierte Patienten (ISS: 43, PTS: 32) mit erheblicher thorakaler Beteiligung (AIS: 5, PTST: 14) und resultierender schwerer Oxygenierungsstörung (paO2/FIO2-Quotient 134 mmHg) entsprechend dem Open Lung Concept (OLC) ventiliert. Es erfolgten die Öffnung der atelektatischen Lungenabschnitte mit einem definierten hohen temporären “Öffnungsdruck” und das “Offenhalten” der rekrutierten Lungenabschnitte mit einem entsprechend hohen PEEP. Ergebnisse. Für das Öffnungsmanöver (ÖM) wurde ein medianer PIP von 65 (51;65) mbar benötigt. Zum Offenhalten der rekrutierten Alveolen war ein medianer Total-PEEP von 22 (20;23) mbar notwendig. Resultierend konnte der Oxygenierungsindex von 134 (96;181) auf 522 (433;587) mmHg signifikant (p<0,001) angehoben werden. Im Verlauf der Behandlung gelang nach dem ÖM die Reduktion von PIP und FIO2. Trotz der Beatmung mit kleinsten Tidalvolumina von 3,5 (3,0;3,9) ml/kg KG gelang sowohl die Aufrechterhaltung des Oxygenierungsniveaus als auch die Gewährleistung einer Normokapnie. Nebenwirkungen hinsichtlich längerfristiger Perfusionsbeeinträchtigungen waren nicht zu verzeichnen. Zwei Patienten (6,25%) verstarben an extrapulmonalen Ursachen. Schlussfolgerung. Das OLC ermöglicht eine suffiziente Behandlung des Ventilations-Perfusions-Missverhältnisses nach Lungenkontusion. Die niedrigen TV- und PIP-Niveaus nach ÖM erfüllten die Ansprüche einer lungenprotektiven Low-Tidalvolume-Ventilation.

Further indications for genetic heterogeneity of euthyroid familial goiter

Iodine deficiency is the most important etiological factor for euthyroid endemic goiter. However, family and twin pair studies also strongly indicate a genetic prediposition. In euthyroid goiters molecular defects in the thyroglobulin (TG), and Na+/I− symporter (NIS) gene have been identified. Numerous mutations in the Pendrin (PDS) gene have been found in families with PDS characterized by deafness and euthyroid goiter. Moreover, family studies indicated two major candidate loci MNG-1 on chromosome 14q31 and Xp22. However, all previous linkage studies investigated only one family. To clarify the general relevance of these previously identified two major candidate loci for the etiology of euthyroid goiter we investigated four families with a total number of 74 family members by linkage analysis with microsatellite markers. Moreover, we analyzed the thyroid candidate genes TG, thyroperoxidase (TPO), NIS, TSH receptor, and PDS. In a further family with 12 members in whom we have previously demonstrated linkage to the MNG-1 locus we investigated the Xp22 locus and the PDS gene in addition to our initial study. Linkage analysis results of our study are not significant enough to definitely exclude or confirm linkage to the investigated candidate genes and loci. Nevertheless, we obtained very weak indications for possible linkage to Xp22 in one family by a maximal multipoint LOD score of 1.15, and cosegregation of haplotypes among affected family members. Moreover, in another family linkage to PDS was indicated by a maximal multipoint LOD score of 1.87 as well as cosegregation of haplotypes. However, sequencing of the PDS gene did not reveal germline mutations. A significant total NPL score of 6.5 for PDS over all families most likely indicated linkage to a genomic region close to PDS. Furthermore, the likelihood of linkage to MNG-1 and Xp22 is reduced, because multipoint LOD scores were below 1 or negative. In all families there was no significant evidence for linkage for the thyroid candidate genes TG, TPO, NIS, or the TSH receptor. In conclusion, a general role of MNG-1 and Xp22 for the etiology of euthyroid goiter is unlikely but cannot clearly excluded. The multipoint parametric and nonparametric LOD scores further suggest genetic heterogeneity in the etiology of familial euthyroid goiter. To identify other susceptibility loci it is necessary to perform genome-wide linkage analysis studies with more families.

Positive End-Expiratory Pressure and Variable Ventilation in Lung-Healthy Rats under General Anesthesia

Objectives Variable ventilation (VV) seems to improve respiratory function in acute lung injury and may be combined with positive end-expiratory pressure (PEEP) in order to protect the lungs even in healthy subjects. We hypothesized that VV in combination with moderate levels of PEEP reduce the deterioration of pulmonary function related to general anesthesia. Hence, we aimed at evaluating the alveolar stability and lung protection of the combination of VV at different PEEP levels. Design Randomized experimental study. Setting Animal research facility. Subjects Forty-nine male Wistar rats (200–270 g). Interventions Animals were ventilated during 2 hours with protective low tidal volume (VT) in volume control ventilation (VCV) or VV and PEEP adjusted at the level of minimum respiratory system elastance (Ers), obtained during a decremental PEEP trial subsequent to a recruitment maneuver, and 2 cmH2O above or below of this level. Measurements and Main Results Ers, gas exchange and hemodynamic variables were measured. Cytokines were determined in lung homogenate and plasma samples and left lung was used for histologic analysis and diffuse alveolar damage scoring. A progressive time-dependent increase in Ers was observed independent on ventilatory mode or PEEP level. Despite of that, the rate of increase of Ers and lung tissue IL-1 beta concentration were significantly lower in VV than in VCV at the level of the PEEP of minimum Ers. A significant increase in lung tissue cytokines (IL-6, IL-1 beta, CINC-1 and TNF-alpha) as well as a ventral to dorsal and cranial to caudal reduction in aeration was observed in all ventilated rats with no significant differences among groups. Conclusions VV combined with PEEP adjusted at the level of the PEEP of minimal Ers seemed to better prevent anesthesia-induced atelectasis and might improve lung protection throughout general anesthesia.

Severe cardiac trauma or myocardial ischemia? Pitfalls of polytrauma treatment in patients with ST-elevation after blunt chest trauma.

Introduction Thoracic injuries are the third most common injuries in polytrauma patients. The mechanism of injury and the clinical presentation are crucially important for adequate emergency treatment. Presentation of case Here we present a case of a 37-year-old male who was admitted to our level-1 trauma center after motor vehicle accident. The emergency physician on scene presented the patient with a myocardial infarction. During initial clinical trauma assessment the patient developed circulatory insufficiency so that cardiopulmonary resuscitation was necessary. Considering the preclinical and clinical course it was decided to proceed with thrombolysis. Despite consistently sufficient resuscitation measures circulatory function was not restored and the patient remained in asystole and passed away. Discussion The initial assessment showed cardiopulmonary instability. After applying thrombolysis a therapeutic point of no return was reached because surgical intervention was impossible but autopsy findings showed severe myocardial and pulmonary contusions likely due to shear forces. Conclusion This case outlines the importance of understanding the key mechanism of injury and the importance of communication at each stage of healthcare transfer. A transesophageal echocardiography can help to identify injuries after myocardial contusion.