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The contribution of veno-venous (VV) extracorporeal membrane oxygenation (ECMO) to systemic oxygen delivery is determined by the ratio of total extracorporeal blood flow (Q˙EC) to cardiac output (Q˙). Thermodilution-based measurements of Q˙may be compromised by blood recirculating through the ECMO (recirculation fraction; Rf). We measured the effects of Q˙ECand Rfon classic thermodilution-based measurements of Q˙in six anesthetized pigs. An ultrasound flow probe measured total aortic blood flow (Q˙A0) at the aortic root. Rfwas quantified with the ultrasound dilution technique. Q˙ECwas set to 0–125% of Q˙A0and Q˙was measured using a pulmonary artery catheter (PAC) in healthy and lung injured animals. PAC overestimated Q˙(Q˙Pa) at all Q˙ECsettings compared to Q˙A0. The mean bias between both methods was 2.1 L/min in healthy animals and 2.7 L/min after lung injury. The difference between Q˙Paand Q˙A0increased with an Q˙ECof 75–125%/Q˙A0compared to QEC<50%/Q˙A0. Overestimation of Q˙Pawas highest when Q˙ECresulted in a high Rf. Thus, thermodilution-based measurements can overestimate cardiac output during VV ECMO. The degree of overestimation of Q˙Padepends on the Q˙EC/Q˙A0ratio and the recirculation fraction.

Der Beitrag untersucht am Beispiel des Engagements für Geflüchtete Stärken, Herausforderungen und Probleme freiwilligen Engagements und arbeitet zugleich die Spezifika dieser Form der Hilfe und Solidarität heraus. Die Analyse rekurriert auf eine qualitative Erhebung, die problemzentrierte Interviews mit Engagierten und Leitfadeninterviews mit Expert*innen sowie eine Dokumentenanalyse von politischen, medialen, zivilgesellschaftlichen und wissenschaftlichen Quellen für den Zeitraum von 2011 bis 2018 umfasst. Im Zentrum der Analyse stehen (1) der mediale und gesellschaftliche Außenblick auf die ehrenamtliche Flüchtlingshilfe, (2) multiple Grenzziehungen, -überschreitungen und -erfahrungen im Engagement sowie (3) die Bewältigung von Problemen und Herausforderungen seitens der Engagierten – durch den Ausstieg aus dem Engagement, die Kritik an Engagementbedingungen, die Verheimlichung des Engagements oder die Politisierung der Rolle freiwilliger Hilfe im Strukturwandel des Wohlfahrtsstaats.

To develop a hybrid augmented marker-based navigation system for acetabular reorientation during peri-acetabular osteotomy (PAO). The system consists of a tracking unit attached to the patient’s pelvis, augmented marker attached to the acetabular fragment and a host computer to do all the computations and visualization. The augmented marker is comprised of an external planar Aruco marker facing toward the tracking unit and an internal inertial measurement unit (IMU) to measure its orientation. The orientation output from the IMU is sent to the host computer. The tracking unit streams a live video of the augmented marker to the host computer, where the planar marker is detected and its pose is estimated. A Kalman filter-based sensor fusion combines the output from marker tracking and the IMU. We validated the proposed system using a plastic bone study and a cadaver study. Every time, we compared the inclination and anteversion values measured by the proposed system to those from a previously developed optical tracking-based navigation system. Mean absolute differences for inclination and anteversion were 1.34 ($$\pm \,1.50$$ ±1.50 ) and 1.21 ($$\pm \, 1.07$$ ±1.07 )$$^\circ $$ ∘ , respectively, for the cadaver study. Mean absolute differences were 1.63 ($$\pm \,1.48$$ ±1.48 ) and 1.55 ($$\pm \,1.49$$ ±1.49 )$$^\circ $$ ∘ for inclination and anteversion for the plastic bone study. In both validation studies, very strong correlations were observed. We successfully demonstrated the feasibility of our system to measure the acetabular orientation during PAO.

Objective To investigate changes in standard base excess (SBE) when administering two different infusion regimens for elective hip replacement within a goal-directed haemodynamic algorithm.Methods This prospective, double-blind, randomized, controlled study enrolled patients scheduled for primary hip replacement surgery, who were randomized to receive either an unbalanced crystalloid (chloride: 155.5 mmol/l) or a 1 : 1 mixture of a balanced crystalloid and a balanced colloid (6% w/v hydroxyethyl starch 130/0.42; chloride: 98 and 112 mmol/l, respectively). Fluid management was goal-directed to optimize stroke volume using oesophageal Doppler.Results A total of 40 patients (19 female/21 male) participated in the study. After surgery, median (25–75% percentiles) SBE was significantly lower in the unbalanced group compared with the balanced group: −2.0 mmol/l (−3.1 to −1.1) versus −0.4 mmol/l (−1.2 to 0.7), respectively. This difference was mainly due to greater plasma chloride concentrations in the unbalanced group. The amount of study medication required to reach haemodynamic stability (median 1200 ml) did not differ between the two groups.Conclusion SBE decreased in the unbalanced group without influence on fluid requirements and haemodynamic stability.

Purpose Combination of prone positioning (PrP) and extracorporeal membrane oxygenation (ECMO) might be beneficial in severe acute respiratory distress syndrome (ARDS), because both approaches are recommended. However, PrP during ECMO might be associated with complications such as dislocation of ECMO cannulae. We investigated complications and change of oxygenation effects of PrP during ECMO to identify “responders” and discuss our results considering different definitions of response in the literature.Methods Retrospective analysis of complications, gas exchange, and invasiveness of mechanical ventilation during first and second PrP on ECMO at specified time points (before, during, and after PrP). We used multivariate nonparametric analysis of longitudinal data (MANOVA) to compare changes of mechanical ventilation and hemodynamics associated with the first and second procedures.Results In 12 ECMO patients, 74 PrPs were performed (median ECMO duration: 10 days (IQR: 6.315.5 days)). No dislocations of intravascular catheters/cannulae, endotracheal tubes or chest tubes were observed. Two PrPs had to be interrupted (endotracheal tube obstruction, acute pulmonary embolism). PaO2/FiO2-ratio increased associated with the first and second PrP (p = 0.002) and lasted after PrP in 58% of these turning procedures (“responders”) without changes in ECMO blood flow, respiratory pressures, minute ventilation, portion of spontaneously triggered breathing, and compliance. Hemodynamics did not change with exception of increased mean pulmonary arterial pressure during PrP and decrease after PrP p=0.001), while norepinephrine dosage decreased (p = 0.03) (MANOVA).Conclusions Prone position during ECMO is safe and improves oxygenation even after repositioning. This might ameliorate hypoxemia and reduce the harm from mechanical ventilation.

Dank der raschen technischen Entwicklung sowie diverser Strategien zur Fehlerbeobachtung und -vermeidung gilt die Intensivmedizin und Anästhesiologie als ein sicheres Fach. Der Verabschiedung der „Patient Safety in the ICU: The Vienna Declaration“ der ESICM vom Oktober 2009 sowie der „Helsinki Declaration on Patient Safety in Anaesthesiology“ der ESA und EBA vom Juni 2010 ist es zu verdanken, dass europaweit festgelegt wurde, welche der erprobten Sicherheitskonzepte als unerlässlich zu werten sind. Viele der allgemein bekannten Strategien haben ihren Ursprung in primär nichtmedizinischen Bereichen, wie beispielsweise der zivilen Luftfahrt, und sind dort nicht mehr wegzudenken. Solche „high reliability organisations“ können diesbezüglich als Vorbilder für das Gesundheitswesen angesehen werden. Critical-Incident-Reporting-Systeme zur Meldung von Beinahezwischenfällen, Crisis-Resource-Management zur Verbesserung von Teamwork und kommunikativen Fähigkeiten sowie Checklisten, wie die WHO-Checkliste, zählen zu konkreten Umsetzungen dieser Art. Des Weiteren wurden standardisierte Medikamentenbeschriftungen, Händedesinfektion, Techniken für die Patientenübergabe und die realitätsnahe Ausbildung am Simulator als Maßnahmen zur Verbesserung der Patientensicherheit exemplarisch für diesen Beitrag ausgewählt.Dank der raschen technischen Entwicklung sowie diverser Strategien zur Fehlerbeobachtung und -vermeidung gilt die Intensivmedizin und Anästhesiologie als ein sicheres Fach. Der Verabschiedung der „Patient Safety in the ICU: The Vienna Declaration“ der ESICM vom Oktober 2009 sowie der „Helsinki Declaration on Patient Safety in Anaesthesiology“ der ESA und EBA vom Juni 2010 ist es zu verdanken, dass europaweit festgelegt wurde, welche der erprobten Sicherheitskonzepte als unerlässlich zu werten sind. Viele der allgemein bekannten Strategien haben ihren Ursprung in primär nichtmedizinischen Bereichen, wie beispielsweise der zivilen Luftfahrt, und sind dort nicht mehr wegzudenken. Solche „high reliability organisations“ können diesbezüglich als Vorbilder für das Gesundheitswesen angesehen werden. Critical-Incident-Reporting-Systeme zur Meldung von Beinahezwischenfällen, Crisis-Resource-Management zur Verbesserung von Teamwork und kommunikativen Fähigkeiten sowie Checklisten, wie die WHO-Checkliste, zählen zu konkreten Umsetzungen dieser Art. Des Weiteren wurden standardisierte Medikamentenbeschriftungen, Händedesinfektion, Techniken für die Patientenübergabe und die realitätsnahe Ausbildung am Simulator als Maßnahmen zur Verbesserung der Patientensicherheit exemplarisch für diesen Beitrag ausgewählt.

Objective This institutional anaesthetic practice evaluation compared patient safety with respect to residual neuromuscular blockade (NMB) at the time of tracheal extubation in patients undergoing high-risk eye surgery.Methods Two muscle relaxation regimens were compared: rocuronium administered via intravenous (i.v.) bolus dosing combined with reversal through sugammadex at end of surgery (group R/S; 17 patients); mivacurium administered via continuous i.v. infusion without antagonization (group M; 22 patients). Train-of-four (TOF) monitoring determined the depth of NMB.Results The TOF ratio at the time of tracheal extubation was greater in group R/S (median 1.03) than in group M (median 0.62). Time from end of surgery to tracheal extubation was not significantly different. The surgeons were 100% satisfied with the working conditions provided under both relaxation regimens.Conclusions Residual postoperative curarization at the time of extubation was frequently observed in group M, whereas there was complete recovery in group R/S. Reversal of NMB by sugammadex provides an additional safety dimension to patient care and should thus be considered especially for those at risk of airway complications or aspiration, in addition to frail patients.

Advanced chronic lung allograft dysfunction limits survival after lung transplantation. We hypothesize that patients with chronic lung allograft dysfunction can be subdivided by exercise tolerance in two groups, and quality of life (QOL) and survival differ between the groups.

OBJECTIVE: This double-blind, prospective, randomized, controlled trial examined the effects of thoracic epidural block and intravenous clonidine and opioid treatment on the postoperative Th1/Th2 cytokine ratio after lung surgery. The primary endpoint was the interferon γ (IFN-γ; Th1 cytokine)/interleukin 4 (IL-4; Th2 cytokine) ratio. Secondary endpoints were reductions in pain and incidence of pneumonia. METHODS: Sixty patients were randomized into three groups to receive remifentanil intravenously (remifentanil group, n= 20), remifentanil and clonidine intravenously (clonidine group, n= 20), or ropivacaine epidurally (ropivacaine group, n= 20). Pain was assessed using a numerical rating scale (NRS). Cytokines were measured using a cytometric bead array. RESULTS: Patients in the ropivacaine group (thoracic epidural block) had a significantly lower IFN-γ/IL-4 ratio at the end of surgery than those in the remifentanil group and clonidine group. There were no significant between-group differences in the IFN-γ/IL-4 ratio at other time-points. There were no differences in NRS scores at any time-point. No patient developed pneumonia. CONCLUSION: Intraoperative thoracic epidural block decreased the IFN-γ/IL-4 ratio immediately after lung surgery, indicating less inflammatory stimulation during surgery.

Context Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry.Objective To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients.Design Single-center prospective randomized controlled trial.Intervention Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages.Main Outcome Measures Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point.Results Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P= .73). Median time to first consultation (P= .60) and frequency of consultation (P= .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0–4.0) than in the home spirometry alone group (4.0; range, 2.0–6.0; P= .04).Conclusion Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

Context—Complications often occur during the early phase after lung transplantation, and rapid diagnosis is vital. Home spirometry is used to detect early changes in graft function. Bluetooth-equipped cell phones are easy to use and facilitate data transfer from home spirometry.Objective—To explore use of home spirometry with Bluetooth data transfer in outpatient lung transplant recipients.Design—Single-center prospective randomized controlled trial.Intervention—Fifty-six patients were randomized either to home spirometry with data transfer via Bluetooth-equipped cell phones or to home spirometry alone before discharge after lung transplantation. In the Bluetooth group, results were transferred to a database capable of generating alarm messages.Main Outcome Measures—Time from onset of symptoms to physician consultation during the first 6 months after lung transplantation was the primary end point.Results—Adherence to home spirometry was 97.2% in the Bluetooth group and 95.3% in the home spirometry alone group (P= .73). Median time to first consultation (P= .60) and frequency of consultation (P= .06) did not differ significantly in the 2 groups. Mean scores on the Hospital Anxiety and Depression Scale were lower in patients in the Bluetooth group (1.5; range, 0.0-4.0) than in the home spirometry alone group (4.0; range, 2.0-6.0; P= .04).Conclusion—Home spirometry with data transfer is feasible and safe in lung transplant recipients. Compared with home spirometry alone, additional data transfer was equally effective regarding the time interval from symptom onset to consultation. Patients in the Bluetooth group reported less anxiety, which may improve emotional well-being.

The authors aimed to test the hypothesis that xenon anesthesia limits adverse hypotensive effects of losartan during acute hemorrhage. In six conscious unsedated Beagle dogs, the systemic and pulmonary circulation were monitored invasively, and two subsequent 60-min hypotensive challenges were performed by (a) induction (propofol) and maintenance of anesthesia with isoflurane/remifentanil or xenon/remifentanil and by (b) subsequent hemorrhage (20 mL kg−1within 5 min) from a central vein. The same amount of blood was retransfused 1 h after hemorrhage. Experiments were performed with or without acute angiotensin II receptor subtype 1 blockade by i.v. losartan (100 g·kg−1·min−1) starting 45 min before induction of anesthesia. Four experiments were performed in each individual dog. Xenon/remifentanil anesthesia provided higher baseline mean arterial blood pressure (85 ± 6 mmHg) than isoflurane/remifentanil anesthesia (67 ± 3 mmHg). In losartan-treated animals, isoflurane/remifentanil caused significant hypotension (42 ± 4 mmHg for isoflurane/remifentanil vs. 71 ± 6 mmHg for xenon/remifentanil). Independent of losartan, hemorrhage did not induce any further reduction of mean arterial blood pressure or cardiac output in either group. Spontaneous hemodynamic recovery was observed in all groups before retransfusion was started. Losartan did not alter the adrenaline, noradrenaline, and vasopressin response to acute hemorrhage. Losartan potentiates hypotension induced by isoflurane/remifentanil anesthesia but does not affect the hemodynamic stability during xenon/remifentanil anesthesia. Losartan does not deteriorate the hemodynamic adaptation to hemorrhage of 20 mL kg−1during xenon/remifentanil and isoflurane/remifentanil anesthesia. Therefore, xenon/remifentanil anesthesia protects against circulatory side effects of losartan pretreatment and thus may afford safer therapeutic use of losartan during acute hemorrhage.

Expert panel consensus was used to develop evidence-based process indicators that were independent risk factors for the main clinical outcome parameters of length of stay in the intensive care unit (ICU) and mortality. In a retrospective, matched data analysis of patients from five ICUs at a tertiary university hospital, agreed process indicators (sedation monitoring, pain monitoring, mean arterial pressure [MAP] ≥ 60 mmHg, tidal volume [TV] ≤ 6 ml/kg body weight, peak inspiratory pressure [PIP] ≤ 35 cmH2O and blood glucose [BG] ≥ 80 and ≤ 130 mg/dl) were validated using a prospective dataset of 4445 consecutive patients. After matching for age, sex and ICU, 634 patients were analysed. Logistic regression of the 634 patients showed that monitoring analgesia and sedation, MAP ≥ 60 mmHg and BG ≥ 80 mg/dl were relevant for survival. Linear regression of the 634 patients showed that analgesia monitoring, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay. Linear regression on all 4445 patients showed analgesia, sedation monitoring, MAP ≥ 60 mmHg, BG ≥ 80 mg/dl and ≤ 130 mg/dl, PIP ≤ 35 cmH2O and TV ≤ 6 ml/kg were associated with reduced length of ICU stay, indicating that adherence to evidence-based key process indicators may reduce mortality and length of ICU stay.

Wachkraniotomien in der Tumor- und Epilepsiechirurgie oder bei der stereotaktischen Elektrodenimplantation für die tiefe Hirnstimulation erfordern spezifische anästhesiologische Strategien. Mit Propofol werden kurze Aufwachzeiten sichergestellt, und die respiratorische Funktion des üblicherweise spontan atmenden Patienten wird nur wenig beeinträchtigt. Die Schmerzausschaltung sollte primär durch einen Hemiskalpblock bei großflächiger Trepanation oder eine lokale Anästhetikainfiltration bei der Tiefenelektrodenimplantation erfolgen. Zusätzlich kann bei einer Trepanation (Tumor- oder Epilepsiechirurgie) Remifentanil in niedriger Dosierung empfohlen werden. Durch einen transnasal eingeführten Tubus, dessen Spitze unter der Epiglottis platziert wird, kann der Atemweg frei gehalten werden. Zum Schutz vor Erbrechen ist eine ausreichende antiemetische Prophylaxe erforderlich.Wachkraniotomien in der Tumor- und Epilepsiechirurgie oder bei der stereotaktischen Elektrodenimplantation für die tiefe Hirnstimulation erfordern spezifische anästhesiologische Strategien. Mit Propofol werden kurze Aufwachzeiten sichergestellt, und die respiratorische Funktion des üblicherweise spontan atmenden Patienten wird nur wenig beeinträchtigt. Die Schmerzausschaltung sollte primär durch einen Hemiskalpblock bei großflächiger Trepanation oder eine lokale Anästhetikainfiltration bei der Tiefenelektrodenimplantation erfolgen. Zusätzlich kann bei einer Trepanation (Tumor- oder Epilepsiechirurgie) Remifentanil in niedriger Dosierung empfohlen werden. Durch einen transnasal eingeführten Tubus, dessen Spitze unter der Epiglottis platziert wird, kann der Atemweg frei gehalten werden. Zum Schutz vor Erbrechen ist eine ausreichende antiemetische Prophylaxe erforderlich.

Das hepatorenale Syndrom (HRS) ist definiert als das Auftreten einer Niereninsuffizienz bei fortgeschrittener Lebererkrankung nach Ausschluss anderer Ursachen einer renalen Funktionsstörung. Die Inzidenz des HRS beträgt bei Patienten mit Aszites 8%, die Gesamthäufigkeit des Nierenversagens liegt in der Endphase des Leberversagens bei 75%. Das Syndrom ist bei fortgeschrittener Lebererkrankung ein wesentlicher prognostischer Faktor. Die Pathogenese des HRS ist komplex, und ihre Aufklärung ist aktuell Gegenstand der Forschung.

We studied the effects of the inhaled endothelin-A receptor antagonist LU-135252 at different doses on hemodynamics and gas exchange in an animal model of acute lung injury. Thirtysix piglets (27 ± 1 kg) were anesthetized, mechanically ventilated (FiO2 1.0), and surfactant-depleted by repeated lung lavage. The animals were randomly assigned to receive either nebulized LU- 135252 for 30 minutes at a dose of 0.3 mg/kg (n = 12), or at a dose of 3.0 mg/kg (n = 12); n = 12 animals received no further treatment (Controls). Induction of acute lung injury decreased PaO2 from 566 ± 8 mmHg to 53 ± 2 mmHg (mean ± SEM) and increased intrapulmonary shunt (QS/QT) from 13 ± 1% to 57 ± 2%. Inhalation of LU-135252 at either dose induced a significant and sustained increase in PaO2 (0.3 mg/kg: 349 ± 39 mmHg; 3.0 mg/kg: 219 ± 40 mmHg), and a significant decrease in QS/QT(0.3 mg/kg: 19 ± 2%; 3.0 mg/kg: 27 ± 3%) when compared with Controls (PaO2: 50 ± 3 mmHg, QS/QT: 50 ± 5%) (P< 0.05; values at 4 hours). Mean pulmonary artery pressure in LU-135252-treated animals (0.3 mg/kg: 31 ± 2 mmHg; 3.0 mg/kg: 30 ± 1 mmHg) was significantly lower than in Controls (40 ± 2 mmHg), while there were no differences in mean arterial pressure and cardiac output. We conclude that inhalation of LU-135252 at either dose improved gas exchange and hemodynamics comparably, indicating that the lower dose was already sufficient to block the majority of endothelin-A receptors in ventilated regions of the injured lung.

Zusammenfassung Die Blutgasanalyse gestattet es, Aussagen über den Säure-Basen-Haushalt und den Gasaustausch zu treffen. Mit Hilfe der direkt gemessenen Werte pH, Sauerstoffpartialdruck (pO 2), Kohlendioxidpartialdruck (pCO 2), O 2-Sättigung und Hämoglobinkonzentration ist es möglich, Werte wie die Bikarbonationenkonzentration, die Basenabweichung und den Sauerstoffgehalt des Blutes zu berechnen (abgeleitete Parameter). Dieser Fortbildungsbeitrag führt in die Messtechnik eines Blutgasgerätes ein und bespricht die Bedeutung der gemessenen Parameter für die Evaluation des Säure-Basen-Haushalts und des Oxygenierungsstatus des Blutes. Abschließend wird auf den Umgang mit Blutgasproben und deren Entnahme eingegangen.

This study compares the haemodynamic and hormonal responses during haemorrhage of conscious dogs pre-treated with an endothelin-A (ET-A) receptor inhibitor. The dogs were studied in two different randomized groups: the control group and a group that was given the ET-A receptor antagonist ABT-627 (as a bolus of 1mg·kg of body weight-1 followed by 0.01mg·kg body weight-1·min-1 intravenously). The time-course was the same for both groups: after a 1h baseline period (pre-haemorrhage), blood (25ml·kg of body weight-1) was withdrawn within 5min. Haemodynamics were continuously recorded and hormone levels measured after 1h (post-haemorrhage). Thereafter, the blood withdrawn was retransfused within 5min and haemodynamics again observed for 1h (post-retransfusion). In ABT-627-treated dogs, the decrease in mean arterial pressure from 87±3 to 64±3mmHg (P<0.05 versus pre-haemorrhage), and cardiac output from 2.1±0.1 to 1.3±0.1l·min-1 (P<0.05 versus pre-haemorrhage) and the increase in systemic vascular resistance from 3286±174 to 4211±230dyn·s·cm-5 (P<0.05 versus pre-haemorrhage) during acute haemorrhage are comparable with controls. During haemorrhage in controls, vasopressin levels increased from 0±0 to 13±2pg·ml-1 (P<0.05 versus pre-haemorrhage), angiotensin II levels increased from 9±1 to 28±9pg·ml-1 (P<0.05 versus pre-haemorrhage) and adrenaline levels increased from 134±22 to 426±74pg·ml-1 (P<0.05 versus pre-haemorrhage) whereas noradrenaline levels did not change (approx. 200 pg·ml-1). In ABT-627-treated dogs, vasopressin levels increased from 0.2±0.0 to 22.2±6.1pg·ml-1 (P<0.05 versus pre-haemorrhage and P<0.05 versus control), angiotensin II levels increased from 8±1 to 37±8pg·ml-1 (P<0.05 versus pre-haemorrhage), noradrenaline levels increased from 147±16 to 405±116pg·ml-1 (P<0.05 versus pre-haemorrhage) and adrenaline levels did not change (200 pg·ml-1) during haemorrhage. We conclude from our results that dogs receiving the selective ET-A inhibitor ABT-627 seem to show a different hormonal response after haemorrhage compared with controls, displaying considerably higher noradrenaline concentrations. Independent of ET-A receptor inhibition, cardiac output during haemorrhage was maintained within the control range. This may indicate that the organism is defending blood flow (cardiac output) over blood pressure during haemorrhage, and that this defence strategy is not compromised by ET-A receptor inhibition.

To investigate the hypothesis that the inhaled ETA receptor antagonist LU-135252 acts as selective pulmonary vasodilator, we compared inhaled LU-135252 and inhaled nitric oxide (iNO) in an experimental model of acute lung injury (ALI), in a prospective, randomized, controlled animal study. A total of 30 anaesthetized, tracheotomized and mechanically ventilated pigs underwent induction of ALI by repeated saline washout of surfactant. The animals were then randomly assigned to receive the nebulized ETA receptor antagonist LU-135252 (0.3mg·kg-1, inhaled over 20min; ETA-A group; n = 10), inhaled NO (30p.p.m. continuously; iNO group; n = 10) or nebulized saline buffer (5ml inhaled over 20min; control group; n = 10). Measurements of pulmonary gas exchange and haemodynamics were performed hourly over a 4h period after induction of ALI. In the ETA-A group, the arterial oxygen tension (Pao2) increased from 58±3 to 377±39mmHg at 4h after intervention, while the intrapulmonary shunt (QS/QT) decreased from 53±4% to 18±2% (P<0.01 compared with controls). In the iNO group, PaO2 increased from 62±4 to 224±48mmHg, and QS/QT decreased from 47±2% to 27±5%, at 4h after induction of ALI (P<0.05 compared with controls). In the ETA-A and iNO groups, the increase in mean pulmonary artery pressure was significantly attenuated compared with controls (ETA-A group, 14±4%; iNO group, 6±4%; values at 4h; P<0.01compared with controls). In contrast, there were no significant differences in changes of mean arterial pressure and cardiac output between groups. Thus, in this experimental model of ALI, both inhaled LU-135252 and iNO significantly improved gas exchange and prevented an increase in mean pulmonary artery pressure, without significant systemic effects, when compared with controls. Our results indicate the occurrence of selective pulmonary vasodilation in both treatment groups.

Acute hypoxia causes hyperventilation and respiratory alkalosis, often combined with increased diuresis and sodium, potassium, and bicarbonate excretion. With a low sodium intake, the excretion of the anion bicarbonate may be limited by the lower excretion rate of the cation sodium through activated sodium-retaining mechanisms. This study investigates whether the short-term renal compensation of hypoxia-induced respiratory alkalosis is impaired by a low sodium intake. Nine conscious, tracheotomized dogs were studied twice either on a low-sodium (LS = 0.5 mmol sodium · kg body wt−1· day−1) or high-sodium (HS = 7.5 mmol sodium · kg body wt−1· day−1) diet. The dogs breathed spontaneously via a ventilator circuit during the experiments: first hour, normoxia (inspiratory oxygen fraction = 0.21); second to fourth hour, hypoxia (inspiratory oxygen fraction = 0.1). During hypoxia (arterial Po234.4 ± 2.1 Torr), plasma pH increased from 7.37 ± 0.01 to 7.48 ± 0.01 (P< 0.05) because of hyperventilation (arterial Pco225.6 ± 2.4 Torr). Urinary pH and urinary bicarbonate excretion increased irrespective of the sodium intake. Sodium excretion increased more during HS than during LS, whereas the increase in potassium excretion was comparable in both groups. Thus the quick onset of bicarbonate excretion within the first hour of hypoxia-induced respiratory alkalosis was not impaired by a low sodium intake. The increased sodium excretion during hypoxia seems to be combined with a decrease in plasma aldosterone and angiotensin II in LS as well as in HS dogs. Other factors, e.g., increased mean arterial blood pressure, minute ventilation, and renal blood flow, may have contributed.

This study investigated whether adenosine mediates the decrease in plasma renin activity (PRA) during acute hypoxia. Eight chronically tracheotomized, conscious beagle dogs were kept under standardized environmental conditions and received a low-sodium diet (0.5 mmol · kg body wt−1· day−1). During the experiments, the dogs were breathing spontaneously via a ventilator circuit: first hour, normoxia (21% inspiratory concentration of O2); second and third hours, hypoxia (10% inspiratory concentration of O2). Each of the eight dogs was studied twice in randomized order in control and theophylline experiments. In theophylline experiments, theophylline, an A1-receptor antagonist, was infused intravenously during hypoxia (loading dose: 3 mg/kg within 30 min, maintenance: 0.5 mg · kg−1· h−1). In theophylline experiments, PRA (5.9 ± 0.8 ng ANG I · ml−1· h−1) and ANG II plasma concentration (15.9 ± 2.3 pg/ml) did not decrease during hypoxia, whereas plasma aldosterone concentration decreased from 277 ± 63 to 132 ± 23 pg/ml (P< 0.05). In control experiments, PRA decreased from 6.8 ± 0.8 during normoxia to 3.0 ± 0.5 ng ANG I · ml−1· h−1during hypoxia, ANG II decreased from 13.3 ± 1.9 to 7.3 ± 1.9 pg/ml, and plasma aldosterone concentration decreased from 316 ± 50 to 70 ± 13 pg/ml (P< 0.05). Thus infusion of the adenosine receptor antagonist theophylline inhibited the suppression of the renin-angiotensin system during acute hypoxia. The decrease in aldosterone occurred independently and is apparently directly related to hypoxia. In conclusion, it is likely that adenosine mediates the decrease in PRA during acute hypoxia in conscious dogs.

In 12 conscious dogs, we investigated whether the angiotensin II-receptor antagonist losartan increases renal sodium excretion and urine volume during controlled mechanical ventilation (CMV) with positive end-expiratory pressure. In four experimental protocols, the dogs were extracellular volume (ECV) expanded (electrolyte solution, 0.5 ml ⋅ kg−1⋅ min−1iv) or not and received losartan (100 μg ⋅ kg−1⋅ min−1iv) or not. They breathed spontaneously during the 1st and 4th hour and received CMV with positive end-expiratory pressure (mean airway pressure 20 cmH2O) during the 2nd and 3rd hours. In the expansion group, dogs with losartan excreted ∼18% more sodium (69 ± 7 vs. 38 ± 5 μmol ⋅ min−1⋅ kg−1) and 15% more urine during the 2 h of CMV because of a higher glomerular filtration rate (5.3 ± 0.3 vs. 4.5 ± 0.2 ml ⋅ min−1⋅ kg−1) and the tubular effects of losartan. In the group without expansion, sodium excretion (2.0 ± 0.6 vs. 2.6 ± 1.0 μmol ⋅ min−1⋅ kg−1) and glomerular filtration rate (3.8 ± 0.3 vs. 3.8 ± 0.4 ml ⋅ min−1⋅ kg−1) did not change, and urine volume decreased similarly in both groups during CMV. Plasma vasopressin and aldosterone increased in both groups, and plasma renin activity increased from 4.9 ± 0.7 to 7.8 ± 1.3 ng ANG I ⋅ ml−1⋅ h−1during CMV in nonexpanded dogs without losartan. Mean arterial pressure decreased by 10 mmHg in nonexpanded dogs with losartan. In conclusion, losartan increases sodium excretion and urine volume during CMV if the ECV is expanded. If the ECV is not expanded, a decrease in mean arterial blood pressure and/or an increase in aldosterone and vasopressin during CMV attenuates the renal effects of losartan.

Acute hypoxic pulmonary vasoconstriction (HPV) may be mediated by vasoactive peptides. We studied eight conscious, chronically tracheostomized dogs kept on a standardized dietary sodium intake. Normoxia (40 min) was followed by hypoxia (40 min, breathing 10% oxygen, arterial oxygen pressures 36 ± 1 Torr) during both control (Con) and losartan experiments (Los; iv infusion of 100 μg ⋅ min−1⋅ kg−1losartan). During hypoxia, minute ventilation (by 0.9 l/min in Con, by 1.3 l/min in Los), cardiac output (by 0.36 l/min in Con, by 0.30 l/min in Los), heart rate (by 11 beats/min in Con, by 30 beats/min in Los), pulmonary artery pressure (by 9 mmHg in both protocols), and pulmonary vascular resistance (by 280 and 254 dyn ⋅ s ⋅ cm−5in Con and Los, respectively) increased. Mean arterial pressure and systemic vascular resistance did not change. In Con, PRA decreased from 4.2 ± 0.7 to 2.5 ± 0.5 ng ANG I ⋅ ml−1⋅ h−1, and plasma ANG II decreased from 11.9 ± 3.0 to 8.2 ± 2.1 pg/ml. The renin-angiotensin system is inhibited during acute hypoxia despite sympathetic activation. Under these conditions, ANG II AT1-receptor antagonism does not attenuate HPV.

Catheter-related infections pose a hazard to both humans and laboratory animals. The aim of this study was to develop a technique preventing bacterial colonization of intravascular catheters.In 27 dogs a total of 70 catheters were implanted. On an average catheters were used for 207 days.Three protocols were compared: (1) flushing the catheters with a heparinized solution; (2) filling only the catheter lumen with α-ctchymotrypsin solution (225 units/ml); (3) filling only the catheter lumen with a solution containing a mixture of the aminoglycoside antibiotic gentamicin (20 mg/ml) and chymotrypsin (225 units/ml).Catheter fillings were always withdrawn before catheter use. Catheter exit sites were all treated with povidone iodine ointment once a day. Body temperatures and weights were recorded, bacteriological and electron microscopical examinations of catheters performed.Without gentamicin filling all catheters were colonized after a few weeks. The dogs showed clinical signs of chronic bacteraemia. Gentamicin filling eradicated colonization. No further bacteraemia was observed.We conclude that filling onlythe catheter lumen with a concentrated solution of chymotrypsin and gentamicin, combined with measures to prevent infections via the subcutaneous catheter tunnel, is an effective and safe technique to prevent catheter-related infections.