Alfons Hammerle

The acute respiratory distress syndrome: definitions, severity and clinical outcome An analysis of 101 clinical investigations

ObjectiveTo determine possible changes in outcome from acute respiratory distress syndrome (ARDS) and to compare severity of lung injury and methods of treatment from 1967 to 1994.Data sourcesComputerized (Medline, Current Contents) and manual (Cumulated Index Medicus) literature search using the key word and/or title ARDS.Study selectionOnly clinical studies published as full papers reporting data on both patient mortality (survival) and oxygenation index (PaO2/FIO2) were included. Single case reports, abstracts, reviews and editorials were excluded from evaluation.Data extractionRelevant data were extracted in duplicate, followed by quality checks on approximately 80% of data extracted.Data synthesis101 papers reporting on 3264 patients were included: 48 studies (2207 patients) were performed in the USA, 43 studies (742 patients) in Europe and 10 studies (315 patients) elsewhere. Mortality reported in these studies was 53±22% (mean±SD), with no apparent trend towards a higher survival (1994: 22 studies, mortality 51±19%). The mean PaO2/FIO2 ratio remained unchanged throughout the observation period (118±47 mmHg). No correlation could be established between outcome and PaO2/FIO2 or lung injury score. Patients who underwent pressure-limited ventilation had a significantly lower mortality (35±20%) than patients on volume-cycled ventilation (54±22%) or patients for whom there was no precise information on ventilatory support (59±19%). Significantly lower PaO2/FIO2 ratios (61±17 mmHg) were observed in patients prior to extracorporeal lung assist, together with mortality rates in the range of those for conventionally treated patients (55±22%).ConclusionsThe mortality of ARDS patients remained constant throughout the period studied. Therefore, the standard for outcome in ARDS should be a mortality in the 50% range. Neither PaO2/FIO2 ratio nor lung injury score was a reliable predictor for outcome in ARDS. Patients might benefit from pressure-limited ventilatory support, as well as extracorporeal lung assist. Since crucial data were missing in most clinical studies, thus preventing direct comparison, we emphasize the importance of using standardized definitions and study entry criteria.

Endothelial cell seeding of polytetrafluoroethylene vascular grafts in humans: A preliminary report

The importance of initial human trials with autologous endothelial seeding lies not only in the implementation of a promising idea but also in the fact that canine data are only partially applicable to humans. The surface area of jugular veins in humans is much smaller than in dogs and considerably longer grafts are needed. Moreover, the reproductive capacity of adult human endothelial cells under in vivo conditions, which probably determines the success of seeding more than the seeding density, is also uncertain. Therefore the efficiency of autologous endothelial seeding in humans was investigated in 18 patients undergoing distal femoropopliteal bypass surgery. The average surface area of the jugular veins was 4.9 +/- 1.7 cm2 with an average cell yield of 32.6 +/- 18.0 x 10(4). The mean number of seeded cells per square centimeter of graft surface was 3.1 x 10(3). In a follow-up extending for 14 weeks, plasma levels of platelet factor 4 and beta-thromboglobulin as well as the platelet function in the whole blood aggregometer showed significantly better results in the seeded group. Plasma thromboxane B2, uptake and survival of indium 111-labeled platelets, and Doppler ultrasound investigations also favored the seeded group, but the results were statistically insignificant. No difference at all was found for the platelet dense granule compounds, releasable adenosine triphosphate and platelet serotonin. Thus our findings did not indicate the development of a closed endothelialized surface after 14 weeks, which is a period three times as long as the one required for confluent endothelial cell coverage in dogs.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous Spinal Anesthesia with a Microcatheter and Low-Dose Bupivacaine Decreases the Hemodynamic Effects of Centroneuraxis Blocks in Elderly Patients

This prospective randomized study was designed to investigate the hemodynamic effects and quality of continuous spinal anesthesia (CSA) after rapid injection of a low dose of 0.5% bupivacaine through a 32-gauge microcatheter. The method was compared with continuous epidural (CEA) and single-dose spinal anesthesia (SSA). Seventy-seven elderly patients (ASA II-III) ranging from 57 to 94 yr old and undergoing lower limb surgery were assigned to CSA (n = 26), CEA (n = 26), and SSA groups (n = 25). In all three groups, mean arterial pressure (MAP) and heart rate (HR) were assessed continuously for 30 min after initial injection, as well as after every reinjection of local anesthetic in the CSA and CEA groups. Bupivacaine (0.5%) was used as a local anesthetic. The initial doses were 1 mL of CSA, 10 mL of CEA, and 3 mL of SSA. The reinjection doses were 1 mL of CSA and 5 mL of CEA. In the CSA group, MAP did not decrease, whereas in the CEA group, the maximum decrease was 15% +/- 3% (mean +/- SEM) for the initial injection, 12% +/- 2% for the first repetition, and 13% +/- 2% for the second repetition. In the SSA group, the largest decrease of MAP was 19% +/- 2%. All changes of MAP in the CEA and SSA groups were significantly larger compared with CSA group (P < 0.05). A total of seven patients in these two groups needed vasopressors due to a decrease of MAP of more than 30% from baseline values. Heart rate did not change.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of pentoxifylline on hemodynamics and oxygenation in septic and nonseptic patients

OBJECTIVE To evaluate the effects of pentoxifylline on hemodynamics and systemic oxygenation in septic and nonseptic critically ill patients. DESIGN Prospective clinical investigation. SETTING Intensive care unit (ICU) of a university hospital. PATIENTS Nineteen critically ill patients were included in the study 1 to 4 days after their admission to the ICU. A systemic inflammatory response syndrome was present in 12 patients, fulfilling at least two of the American College of Chest Physicians/ Society of Critical Care Medicine Consensus Conference criteria. The other seven patients did not fulfill these criteria and were classified as nonseptic. INTERVENTIONS All patients were mechanically ventilated. The dosage of catecholamines was kept constant during the entire study period and at least during 15 mins before the start of the study. In both study groups, pulmonary and radial artery catheters were inserted and 5 mg/kg of pentoxifylline (diluted in 300 mL of physiologic saline) was intravenously administered over a period of 180 mins at a rate of 100 mL/hr. MEASUREMENTS AND MAIN RESULTS Hemodynamic variables, oxygen transport (DO2), oxygen uptake (VO2), and oxygen extraction ratio were determined before pentoxifylline, after 2.5 mg/kg of pentoxifylline, after 5 mg/kg of pentoxifylline, and 60 mins after the termination of pentoxifylline. Repeated-measures analysis of variance and Mann-Whitney test were used for statistical analysis. At baseline, there were significant differences between the septic and the nonseptic groups in mean pulmonary arterial pressure (septic: 31 +/- 5 mm Hg; nonseptic: 26 +/- 7 mm Hg, p < .05), and pulmonary vascular resistance index (PVRI) (septic: 344 +/- 121 dyne.sec/ cm5.m2; nonseptic: 233 +/- 100 dyne.sec/cm5.m2, p < .05). In the septic group, significant increases in heart rate and cardiac index were observed. Systemic vascular resistance index and PVRI decreased. No significant changes in hemodynamic variables occurred in the nonseptic group. In both groups, DO2 and VO2 increased significantly, while oxygen extraction ratio remained unchanged. CONCLUSIONS The administration of pentoxifylline to septic patients results in a significant improvement in hemodynamic performance compared with critically ill nonseptic patients. The better hemodynamic state is accompanied by an increase in DO2 and VO2 with unchanged oxygen extraction ratio.

Right ventricular function in early septic shock states

ObjectivesTo define a variable which could reliability predict when fluid resuscitation as monotherapy is not expected to improve organ perfusion pressure, owing to limitations in cardiac output responsiveness in patients with severe sepsis.DesignProspective controlled trial.SettingAnesthesiological ICU in a university hospital.PatientsTwenty seven patients in early septic shock states (MAP<60 mmHg).InterventionsInfusion therapy was titrated until no further increase in cardiac index and mean arterial pressure could be achieved. Fluid resuscitation as monotherapy was deemed unsuccessful at the end of 2 h if inotropic or vasoactive pharmacologic support was required to maintain a mean arterial pressure > 60 mmHg.Measurements and resultsWe investigated the hemodynamic course during fluid resuscitation (2850±210 ml crystalloids) with special emphasis on right heart function using the thermodilution technique. Eleven patients (group A) had a right ventricular (RV) ejection fraction below 45%. In this group positive inotropic and/or vasoactive drugs were obligatory to achieve and maintain a sufficient perfusion pressure (MAP>60 mmHg) after fluid challenge.ConclusionsIn 27 septic shock patients investigated, we diagnosed right ventricular dysfunction in 41%. In this specific patient population fluid replacement alone did not succeed in stabilizing hemodynamic variables, therefore necessitating catecholamine therapy.

The relationship between oxygen delivery and uptake in the critically ill : is there a critical or optimal therapeutic value ? A meta-analysis

In order to identify a critical or an optimal therapeutic value for oxygen delivery and oxygen uptake, we analysed data from 40 publications concerning the relationship between oxygen delivery and consumption in patients with adult respiratory distress syndrome, trauma or during sepsis, and in nonseptic controls. According to the outcome, the patients were allocated to either group 1 (survivors) or group 2 (nonsurvivors). While oxygen delivery and uptake (mean, SEM) were significantly higher in patients with adult respiratory distress syndrome (636, SEM 31 ml.min‐1.m‐2and 155, SEM 5 ml.min‐1.m‐2), trauma (782, SEM 77 ml.min‐1.m‐2 and 167, SEM 10 ml.min‐1.m‐2) and sepsis (654, SEM 28 ml.min‐1.m‐2 and 163, SEM 5 ml.min‐1.m‐2) than in nonseptic controls (452, SEM 18 ml.min‐1.m‐2 and 126, SEM 3 ml.min‐1.m‐2, p < 0.05), there were no significant differences in these parameters between survivors and nonsurvivors. Although therapeutic manoeuvres were effective in increasing both oxygen delivery and consumption, these improvements were not parallelled by an increase in survival rate. The correlation between oxygen delivery and uptake is generally a result of the use of pooled data and therefore prone to mathematical coupling. This is true particularly for patients with adult respiratory distress syndrome and sepsis. Thus, our study failed to identify either an optimal or a critical value of oxygen delivery or oxygen consumption in critically ill patients.

In vivo modulation of human neutrophil function by pentoxifylline in patients with septic syndrome.

The influence of pentoxifylline on human polymorphonuclear granulocyte (PMN) respiratory burst activity (RBA) was studied in 23 patients fulfilling the established criteria of sepsis and in 10 healthy donors. Pentoxifylline (PTX) was administered (5 mg/kg) by intravenous infusion in 13 septic patients over a period of 180 min. The control group consisted of 10 patients with septic syndrome who received an infusion of physiological saline. For determination of RBA, 10 mL of blood was drawn at respective time intervals before, during, and after treatment with PTX or a placebo. RBA measurements were performed using a chemiluminescence assay after stimulation of PMN with formyl-methionyl-leucyl-phenylalanine (FMLP), phorbol-myristate-acetate, and opsonized zymosan, respectively. RBA measurements of each patient were performed in replicate samples. CL was measured for 1 h at respective time intervals (1, 3, 5, 8, 10, 15 min etc.). RBA of PMN of septic patients was compared with RBA of PMN of healthy donors and patients receiving PTX were compared with controls. Our results demonstrate that PMN of patients with sepsis had an increased oxidative response compared with healthy donors. We found that PTX administered intravenously was able to reduce this reactivity. RBA was significantly decreased during PTX infusion when PMN were stimulated with FMLP and phorbol-myristate-acetate, compared with the control group. No significant decrease was observed when PMN were stimulated with opsonized zymosan. These data suggest that PTX may be a valuable drug in septic state.

Right ventricular function and oxygen transport patterns in patients with acute respiratory distress syndrome

We investigated the impact of right ventricular performance on oxygen kinetics in 15 consecutive patients with acute respiratory distress syndrome. Six hundred and twenty‐two complete assessments of haemodynamics, right ventricular function and oxygenation were used for evaluation. Patients were grouped as survivors (n = 8) and nonsurvivors (n = 7) and studied during four phases of lung failure. Oxygen delivery and consumption were significantly higher in survivors compared to nonsurvivors despite comparable arterial oxygen saturation. Right ventricular end‐diastolic volumes were similar for both groups, while end‐systolic volumes were significantly higher in nonsurvivors due to depressed ejection fraction (40.5 (SD 1.2) versus 34.4 (SD 2.8)%) during all phases of lung failure. No clinically relevant differences in right ventricular function or oxygenation were observed between periods of moderate or severe pulmonary hypertension. Nonsurvivors have depressed cardiac function caused by reduced contractility and not by inadequate right ventricular end‐diastolic volume (preload) or increased pulmonary artery pressure (afterload). Maintenance of oxygen delivery in ARDS is predominantly a function of cardiac performance and not of pulmonary gas exchange.

Optimal values for oxygen transport during hypothermia in sepsis and ARDS

Mild hypothermia (33 °C to 35. 5 °C) is reported to improve oxygenation and survival in patients with lung failure (1). Although hypermetabolism may account for about 50% of the ventilatory demand in ARDS patients, the concept of reducing oxygen consumption (VO2) by lowering metabolic rate, has only recently gained attention (2). Our study was aimed to test whether mild hypothermia established by continuous veno‐venous haemofiltration (CVVHF), could optimize values for oxygen kinetics in ARDS patients.

Severity and Outcome of ARDS: The Present Place of Extracorporeal Lung Assist (ECLA)

Within the last decade extracorporeal lung assist has been recommended for the treatment of acute respiratory distress syndrome. However, this recommandation was challenged by several recent clinical studies and reviews. The goal of our analysis was therefore to investigate data on outcome and severity of gas exchange disturbance published from patients treated with ECLA. These data were compared to a historical control group consisting of ARDS patients treated conventionally. Computerized (MEDLINE 1967-95) literature search using the keywords ARDS, ECLA, ECMO, ECCO2R and HUMAN was performed. Only clinical studies published as full papers reporting data on both, patients mortality and oxygenation index (PaO2/FiO2) were included. Overall mean mortality reported was 53±22% in 17 studies (419 patients), with no apparent trend towards a higher survival within the last decade with a mean PaO2/FIO2 (14 papers; 61±17 mmHg). However, mean mortality rates of ARDS patients requiring ECLA was 52.3% and 44.9% if patients undergoing ECMO were excluded (3 papers). Therefore the mortality of these patients with severe lung injury was in the range of patients treated conventionally. Patient outcome observed in our analysis is in accordance with the mortality rates from the European ECLA centres published recently (49% in 1993). Therefore, we conclude that the mean mortality rate of patients suffering from severe ARDS treated with ECLA is in the 50% range and does not differ significantly from those of patients treated conventionally, despite significantly poorer pulmonary function.