Predictors of respiratory function deterioration after transfer of critically ill patients.

OBJECTIVES: Critically ill patients are often transferred due to the growing number of diagnostic procedures required to be performed outside the intensive care unit. These transfers have proved to be very critical. The aim of this study was to evaluate predictors for the deterioration of respiratory function in critically ill patients after transfer. DESIGN: Prospective, clinical, observational study. SETTING: 1800-bed university teaching hospital. SUBJECTS: 98 mechanically ventilated patients were investigated during transfer. MEASUREMENT AND MAIN RESULTS: Before transfer, all patients were classified according to the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Therapeutic Intervention Scoring System (TISS). Haemodynamics and arterial blood gases were measured at 11 different times. Arterial oxygen tension (PaO2), fractional inspired oxygen (FIO2), PaO2/FIO2 ratio, lowest PaO2/FIO2 ratio, minimal PaO2 and maximal FIO2, APACHE II score, TISS before transfer, age and duration of transfer were analysed as potential predictors for deterioration of respiratory function after transfer. Variables were analysed using Classification and Regression Trees and Clustering by Response. In 54 transports (55%) there was a decrease in the PaO2/FIO2 ratio, and a decrease of more than 20% from baseline was noted in 23 of the transferred patients (24%). Age > 43 years and FIO2 > 0.5 were identified as predictors for respiratory deterioration. CONCLUSIONS: Our predictors were able to indicate deterioration after transfer correctly in 20 of 22 patients (91%), combined with a false-positive rate in 17 of 49 (35%).

Hydroxyethyl starch and modified fluid gelatin maintain plasma volume in a porcine model of septic shock with capillary leakage.

OBJECTIVE: To compare the effects of different volume replacement therapies on maintenance of plasma volume in septic shock and capillary leakage syndrome. DESIGN AND SETTING: Prospective randomized, controlled animal laboratory study in a university animal laboratory. MEASUREMENTS AND RESULTS: Twenty-five fasted, anaesthetized, mechanically ventilated and multi-catheterized pigs (20.8+/-1.8 kg) received 1 g/kg body weight faeces into abdominal cavity to induce sepsis and were observed over 8 h. Five animals each received volume replacement therapy with modified fluid gelatin 4% or 8% (MFG4%, MFG8%), 6% HES 200/0.5, or Ringer's solution and were compared to controls receiving 6% HES 200/0.5. Infusion rate was titrated to maintain a central venous pressure of 12 mmHg. Plasma volume was determined using (51)Cr-labelled erythrocytes and standard formulae. Albumin escape rate was calculated using technetium (99m)Tc-labelled albumin. Colloid osmotic pressure, systemic haemodynamics and oxygenation were obtained before and 4 and 8 h after induction of sepsis. Plasma volume was reduced in the Ringer's solution group (-46%) but was maintained in HES (+/-0%), MFG4% (+4%), MFG8% (+23%) groups. Albumin escape rate increased in HES (+52%), MFG4% (+47%), MFG8% (+54%) and the Ringer's solution group (+41%) compared to controls. CONCLUSION: In this porcine septic shock model with concomitant capillary leakage syndrome, confirmed by an increased albumin escape rate, the artificial colloids HES, MFG4%, and MFG8% maintained plasma volume and colloid osmotic pressure. These results suggest the intravascular persistency of artificial colloids in the presence of albumin leakage. An editorial regarding this article can be found in the same issue (http://dx.doi.org/10.1007/s00134-002-1283-9)

Septic shock after liver transplantation for Caroli's disease: clinical improvement after treatment with C1-esterase inhibitor.

The extent of complement and contact activation is related to outcome in sepsis. A low functional index of their main blocker C1-esterase inhibitor (C1-INH) is considered as a relative deficiency of C1-INH and might contribute to the development of fatal complications in the intensive care unit. The first results of therapeutic intervention with C1-INH concentrate in septic shock are promising. We report on our experience of C1-INH concentrate administration in a young woman with Caroli's disease as ultimate rescue therapy for septic shock with capillary leakage syndrome after combined liver and kidney transplantation. No focus of infection was detectable and thus surgical intervention was not indicated. Antibiotic therapy at that time included vancomycin, tobramycin, meropenem and fluconazol. Hemodynamic stabilization occurred within hours after administration of C1-INH concentrate. Simultaneously a reduction in vasopressor medication was possible and negative fluid balance was achieved.

Effects of C1 inhibitor and r-SP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury.

OBJECTIVE: To assess the effects of C1 inhibitor (INH) administration and r-SP-C surfactant application on oxygenation and lung histology in an acute respiratory distress syndrome model. DESIGN AND SETTING: Randomized, controlled experimental study in an animal research laboratory. MATERIAL: 36 adult male Sprague-Dawley rats. INTERVENTIONS: Animals were subjected to repetitive lung lavage. Four experimental groups and two control groups were studied: groups 1 and 2 served as controls. Animals of groups 3-6 received 200 U/kg body weight C1-INH (group 3), 25 mg/kg r-SP-C surfactant (group 4) or both (group 5) at 60 min postlavage (pl). Animals of group 6 were treated with 200 U/kg C1-INH1 at 10 min pl. Animals of group 1 were killed 60 min (min) pl, animals of groups 2-6 were killed at 210 min pl. Thereafter the lungs were excised for histological examination. MEASUREMENTS AND RESULTS: Hyaline membrane formation, intra-alveolar neutrophil (PMN) accumulation and intra-alveolar/perivascular haemorrhage were graded semiquantitatively (0-4). Blood gases were determined 120, 150, 180 and 210 min pl. At 210 min pl pO(2) in group 4 (456+/-74 mmHg) and group 5 (387+/-155 mmHg) was significantly higher than in controls (72+/-29 mmHg) or after C1-INH monotherapy (group 3: 120+/-103, group 6: 63+/-12 mmHg). PMN infiltration after C1-INH monotherapy was significantly less severe than in controls. The combination of r-SP-C surfactant and C1-INH led to significantly lower PMN infiltration than surfactant monotherapy. CONCLUSION: In this lavage-induced acute respiratory distress syndrome model the administration of C1-INH might be followed by a higher clinical efficacy of exogenously supplied recombinant SP-C surfactant.

[Circulatory function and oxygenation during hemihepatectomy. Dopamine versus dopexamine]. / Kreislaufverhalten und Oxygenierung während Hemihepatektomien. Dopamin versus Dopexamin.

OBJECTIVE: The aim of this study was to compare low dose dopamine and dopexamine with respect to of liver-venous oxygen saturation, oxygen delivery and--demand, liver function tests and cardiocirculatory effects in the reperfusion period during a hemihepatectomy operation with occlusion of the liver hilus. METHODS: Twenty patients were studied in a randomised, doubleblind setting. They either received 2 micrograms/kg per min dopamine or 0.5 microgram/kg per min dopexamine perioperatively. For monitoring purposes a pulmonary artery and a liver venous catheter were placed. At four different time points hemodynamic parameter were assessed and blood samples were drawn. RESULTS: Significant changes between groups were found 5 min after opening the liver hilus for the cardiac index and the systemic oxygen delivery, as well as at the end of the operation for pulmonary shunt volume, which had increased more in the dopexamine group. No significant difference between liver venous oxygen saturation and liver function tests was found. CONCLUSION: Until more detailed studies concerning the influence of dopamine on the hepatic-splanchnic region during liver surgery are performed, dopexamine can not be considered superior to dopamine during these operations.

Xenon inhalation increases airway pressure in ventilated patients.

BACKGROUND: The inert gas xenon, known as an anaesthetic for nearly 50 years, is also used as a contrast agent during computerised tomography (CT)-scanning. As xenon has a higher density and viscosity than air, xenon inhalation may increase airway resistance. METHODS: In a retrospective study we investigated the effects of 33% xenon/67% oxygen on airway pressure and cardio-respiratory parameters in 37 long-term mechanically ventilated patients undergoing cerebral blood flow (rCBF) measurements by means of stable xenon-enhanced CT. RESULTS: Xenon administration caused a significant increase in peak airway pressure from 31.6+/-8.0 cm H2O to 42.7+/-16.9 cm H2O. This effect was reproducible, did not occur after reduction of inspiratory flow rate by 50% from 0.56+/-0.15 L x s(-1) to 0.28+/-0.08 L x s(-1), and vanished immediately after termination of xenon delivery. CONCLUSION: Due to the higher density and viscosity of this gas mixture, ventilation with xenon/oxygen produces a higher Reynolds' number than oxygen/air when given at the same flow rate. This means that during xenon ventilation the zone of transition from turbulent to laminar gas flow may be located more peripherally (in smaller airways) than during oxygen/air ventilation with a subsequent increase in airway resistance. Our results indicate that xenon inhalation may cause a clinically relevant increase of peak airway pressure in mechanically ventilated patients.

Low-dose dopexamine in patients undergoing hemihepatectomy: an evaluation of effects on reduction of hepatic dysfunction and ischaemic liver injury.

BACKGROUND: Hepatic dysfunction is a common problem in patients after hemihepatectomy. Treatment with low-dose dopamine has been shown to be beneficial in hemihepatectomy patients. We hypothesized that dopexamine, a synthetic vasoactive catecholamine, due to its specific pharmocodynamic profile may be more effective in reducing hidden ischaemic episodes in the hepato-splanchnic region during and after temporary total cross-clamping of hepatic inflow in these patients. METHODS: The effects of low-dose dopexamine on hepatic venous haemoglobin oxygen saturation (ShvO2), hepatic venous lactate level, monoethylglycinxylid (MEGX) formation, hepatic synthetic function and indicators for hepatic cell damage were studied during hemihepatectomy and for 16 h postoperatively in hemihepatectomy patients and compared to those of low-dose dopamine. In a prospective, double-blind clinical study 20 patients received randomly either dopexamine (DPX) 0.5 microg kg(-1) min(-1) (n=10) or dopamine (DO) 2.5 microg kg(-1) min(-1) (n= 10). Infusions were started after induction of anaesthesia and continued 16 h postoperatively. Hepatic vein, radial and pulmonary artery were catheterized. Measurements were carried out after induction of anaesthesia, after total cross-clamping of hepatic inflow, and at 2 h and 16 h postoperatively. RESULTS: There were no differences in systemic haemodynamics, oxygenation, ShvO2, serum aminotransferases or MEGX levels between the groups. At 16 h postoperatively prothrombin and antithrombin III levels were significantly lower while hepatic venous lactate was significantly higher in the DPX group compared to the DO group. CONCLUSION: In patients undergoing hemihepatectomy, we could not reveal superior hepatoprotective effects of low-dose dopexamine compared to low-dose dopamine.

Compositional, structural, and functional alterations in pulmonary surfactant in surgical patients after the early onset of systemic inflammatory response syndrome or sepsis.

OBJECTIVES: Sepsis is one of the most important predisposing factors for the development of the acute respiratory distress syndrome (ARDS). Alterations of pulmonary surfactant contribute in the pathogenesis of ARDS. However, little is known about surfactant in patients with less severe grades of lung injury related to sepsis or systemic inflammatory response syndrome (SIRS). Therefore, the purpose of this study was to characterize endogenous surfactant in surgical intensive care patients with sepsis or SIRS. DESIGN: Prospective, observational study. SETTING: University-affiliated, interdisciplinary intensive care unit. PATIENTS: Eleven patients after major surgery with SIRS or sepsis included within 12 hrs of onset and 11 controls without infection or lung disease. INTERVENTIONS: Operating room and standard intensive care unit management. MEASUREMENTS AND MAIN RESULTS: Four serial bronchoalveolar lavage samples (BAL) were recovered over 7 days from the patients and single BAL samples were obtained from controls. BAL cells, total protein, surfactant-associated protein A (SP-A), surfactant alveolar transition forms, and surface activity were analyzed. Two of 11 patients met criteria for acute lung injury and six of the 11 patients met ARDS consensus conference criteria but acute lung injury or ARDS was not persistent. The mean Pao2/F(IO)2 for the patients over 7 days was 253.2+/-15.1 (SEM) and Murray's lung injury score was 1.12+/-0.12, indicating mild-to-moderate lung injury. BAL neutrophil counts were increased (p< .01), and the ratio of poorly functioning light aggregate surfactant to superiorly functioning heavy aggregate surfactant was increased compared with controls (0.32+/-0.06 vs. 0.09+/-0.01, p < .05). SP-A was decreased (1.9+/-0.4 vs. 3.5+/-0.6 microg/mL of BAL, p< .05) and there were increases in the ratios of phospholipid to SP-A (p < .05), protein to SP.A (p < .01), and protein to phospholipid (p < .05). The surface tension-lowering ability of purified heavy aggregate surfactant was significantly impaired (15.6+/-1.6 vs. 2.8+/-0.6 milliNewtons/m, p< .05). CONCLUSIONS: These observations show that surgical patients with SIRS or sepsis who have mild-to-moderate lung injury develop surfactant dysfunction detectable within 7 days of onset. We propose, therefore, that therapeutic strategies to modulate these severe surfactant abnormalities should be considered, as these strategies may have the potential to reduce lung injury, which is associated with a high mortality in sepsis.

C1-Inhibitor for treatment of acute vascular xenograft rejection in cynomolgus recipients of h-DAF transgenic porcine kidneys.

At present, the major barrier to successful discordant xenotransplantation of unmodified or complement regulator transgenic porcine xenografts is acute vascular xenograft rejection (AVR). AVR is associated with the intragraft deposition of induced recipient xenoreactive antibodies and subsequent complement activation. In a life-supporting pig to primate kidney xenotransplantation setting using h-DAF transgenic donor organs and postoperative immunosuppression, episodes of AVR were either treated with boluses of cyclophosphamide and steroids or with the same regimen supplemented by a three-day course of C1-Inhibitor, a multifunctional complement regulator. In 8 out of 10 animals stable initial graft function was achieved; in all animals one or more episodes of AVR were observed. When, in 4 animals, C1-Inhibitor was added to the standard anti-rejection treatment regimen, AVR was successfully reversed in 6 out of 7 episodes, while in another group of 4 animals receiving the standard anti-rejection treatment 0 out of 4 episodes of AVR responded to treatment. Response to anti-rejection treatment was associated with a significant increase in recipient survival time. We conclude that AVR of h-DAF transgenic porcine kidneys can be successfully treated by additional short-term fluid phase complement inhibition.