[Interdisciplinary COVID board for patients with SARS-CoV-2-triggered hyperferritinemic Inflammation]. / Interdisziplinäres COVID-Board bei SARS-CoV-2-getriggerter hyperferritinämischer Inflammation.

BACKGROUND: Patients with severe COVID-19 develop hyperferritinemic inflammation, a rare sepsis-like immune dysregulation syndrome. METHODS: Stratified treatment decisions in a cross-location telemedical interdisciplinary case conference were assessed in this retrospective cohort study. A standardized treatment algorithm including continuous positive airway pressure and noninvasive ventilation was implemented. A locally developed COVID inflammation score (CIS) defined patients at risk for severe disease. Patients with life-threatening inflammation were offered off-label treatment with the immune modulator ruxolitinib. RESULTS: Between 4 March 2020 and 26 June 2020 COVID-19 patients (n = 196) were treated. Median patient age (70 years) and comorbidity were high in interstudy comparison. Mortality in all patients was 17.3%. However, advance care planning statements and physician directives limited treatment intensity in 50% of the deceased patients. CIS monitoring of ruxolitinib-treated high-risk patients (n = 20) on days 5, 7, and15 resulted in suppression of inflammation by 42% (15-70), 54% (15-77) and 60% (15-80). Here, mortality was 20% (4/20). Adjusted for patients with a maximum care directive including ICU, total mortality was 8.7% (17/196). CONCLUSION: Severe COVID-19 pneumonia with hyperferritinemic inflammation is related to macrophage activation syndrome-like sepsis. An interdisciplinary intensive care teleconference as a quality tool for ICUs is proposed to detect patients with rare sepsis-like syndromes.

Disparities in Opioid Pain Management for Long Bone Fractures.

An expanding body of evidence has established that racial disparities exist in the US healthcare system, manifesting in poorer health outcomes for members of the non-white population. This study examines whether disparities exist in the type of analgesia ordered for long bone fractures and the time to medication administration in a community teaching hospital serving a large Hispanic population. We reviewed de-identified data of 115 patients from the emergency department of a community Level II Trauma Center in central Florida with diagnosed long bone fractures and examined the clinical and demographic variables associated with the type of analgesic administered and factors associated with delays in medication administration. We found that women reported higher pain scores than men, but there was no difference in the type of pain medication administered. There was no difference in pain scores between white and non-white patients; however, white patients were more likely to receive opiates for their long bone fractures compared with non-white patients (70 vs 50%, p < 0.0001). Opioid pain medications were prescribed significantly more often to adult and elderly patients compared with pediatric patients who were more likely to receive acetaminophen compared with both other patient groups (p < 0.001). In summary, we found that pain score was not associated with the class of pain medication administered, but that race and age were. This study questions the utility of the pain score for acute injuries and raises concerns about the role of physician bias in analgesia administration.

Bronchoscopic administration of bovine natural surfactant in ARDS and septic shock: impact on gas exchange and haemodynamics.

The aim of the present study was to investigate the feasibility and efficacy of bronchoscopic surfactant administration in a noncontrolled multicentre study in five university centres. A total number of 27 patients, suffering from severe acute respiratory distress syndrome (mean+/-SEM lung injury score: 3.15+/-0.06) and septic shock (Acute Physiology and Chronic Health Evaluation (APACHE) II score at study entry 33.2+/-1.3, lactate 4.3+/-0.6 mmol x L(-1)) were studied. The patients were ventilated with a mean tidal volume of 11.0+/-0.5 mL x kg(-1) body weight (bw), either volume or pressure controlled, with 16.3+/-2.8 cmH2O positive end-expiratory pressure, for an average of 3.5+/-0.3 days at study entry. A natural bovine surfactant extract (300 mg x kg(-1) bw Alveofact; mean total volume 378 mL) was delivered in divided doses to each segment of the lungs via flexible bronchoscope within approximately 45 min. No untoward effects on gas exchange, lung mechanics and haemodynamics were noted during the procedure of surfactant administration. Within 12 h the oxygen tension in arterial blood/inspiratory oxygen fraction increased from a mean of 109+/-8 mmHg to 210+/-20 mmHg (p<0.001). In seven patients, in whom gas exchange again deteriorated with further progression of the disease, a second surfactant dose of 200 mg x kg(-1) was administered 18-24 h after the first application, again improving arterial oxygenation. A total of 15 patients survived the 28-day study period (mortality rate 44.4%, compared to a calculated risk of death for the given APACHE II scores of 74.0+/-3.5%), with all causes of death being nonrespiratory. The bronchoscopic application of a high dose of natural surfactant in patients with severe acute respiratory distress syndrome and septic shock is both feasible and safe, resulting in a pronounced improvement in gas exchange.

Is pulmonary resistance constant, within the range of tidal volume ventilation, in patients with ARDS?

When managing patients with acute respiratory distress syndrome (ARDS), respiratory system compliance is usually considered first and changes in resistance, although recognized, are neglected. Resistance can change considerably between minimum and maximum lung volume, but is generally assumed to be constant in the tidal volume range (V(T)). We measured resistance during tidal ventilation in 16 patients with ARDS or acute lung injury by the slice method and multiple linear regression analysis. Resistance was constant within V(T) in only six of 16 patients. In the remaining patients, resistance decreased, increased or showed complex changes. We conclude that resistance within V(T) varies considerably from patient to patient and that constant resistance within V(T) is not always likely.

Radioisotope albumin flux measurement of microvascular lung permeability: an independent parameter in acute respiratory failure?

AIM: To evaluate the extent to which single measurements of microvascular lung permeability may be relevant as an additional parameter in a heterogenous clinical patient collective with Acute Lung Injury (ALI) and Acute Respiratory Distress Syndrome (ARDS). METHODS: In 36 patients with pneumonia (13), non pneumogenic sepsis (9) or trauma (14) meeting the consensus conference criteria of ALI or ARDS double-isotope protein flux measurements (51Cr erythrocytes as intravascular tracer, Tc-99m human albumin as diffusible tracer) of microvascular lung permeability were performed using the Normalized Slope Index (NSI). The examination was to determine whether there is a relationship between the clinical diagnosis of ALI/ARDS, impaired permeability and clinical parameters, that is the underlying disease, oxygenation, duration of mechanical ventilation and mean pulmonary-artery pressure (PAP). RESULTS: At the time of study, 25 patients presented with increased permeability (NSI > 1 x 10(-3) min-1) indicating on exudative stage of disease, and 11 patients with normal permeability. The permeability impairment correlated with the underlying disease (p > 0.05). With respect to survival, there was a negative correlation to PAP (p < 0.01). Apart from that no correlations between the individual parameters were found. Especially no correlation was found between permeability impairment and oxygenation, duration of disease or PAP. CONCLUSION: In ALI and ARDS, pulmonary capillary permeability is a diagnostic parameter which is independent from clinical variables. Permeability measurement makes a stage classification (exudative versus non exudative phase) of ALI/ARDS possible based on a measurable pathophysiological correlate.

[10 years experience with extracorporeal membrane oxygenation]. / Zehn Jahre Erfahrung mit extrakorporaler Membranoxygenierung (ECMO).

OBJECTIVE: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used for severe acute respiratory distress syndrome (ARDS). We present outcome, clinical parameters, and complications in a cohort of 245 ARDS patients of whom 62 were treated with ECMO. METHODS: Data of all ARDS patients were prospectively collected between 1991 and 1999. Outcome and clinical parameters of patients treated with and without ECMO were evaluated. RESULTS: Hundred-thirty-eight patients were referred from other hospitals, 107 were primarily located in our hospital. About one fourth of these patients was treated with ECMO. The survival rate was 55% in ECMO patients and 61% in non-ECMO patients. ECMO resulted in very few complications, one of them was fatal. No parameter before or during ECMO could be used to predict the individual prognosis. CONCLUSION: ECMO is a therapeutic option for patients with severe ARDS, likely to increase survival. However, a randomized controlled study proving its benefit is still awaited. Until the development of a causal or otherwise superior therapy ECMO should be used in selected patients.

Volume-dependent compliance and ventilation-perfusion mismatch in surfactant-depleted isolated rabbit lungs.

OBJECTIVE: Volume-dependent alterations of lung compliance are usually studied over a very large volume range. However, the course of compliance within the comparably small tidal volume (intratidal compliance-volume curve) may also provide relevant information about the impact of mechanical ventilation on pulmonary gas exchange. Consequently, we determined the association of the distribution of ventilation and perfusion with the intratidal compliance-volume curve after modification of positive end-expiratory pressure (PEEP). DESIGN: Repeated measurements in randomized order. SETTING: An animal laboratory. SUBJECTS: Isolated perfused rabbit lungs (n = 14). INTERVENTIONS: Surfactant was removed by bronchoalveolar lavage. The lungs were ventilated thereafter with a constant tidal volume (10 mL/kg body weight). Five levels of PEEP (0-4 cm H2O) were applied in random order for 20 mins each. MEASUREMENTS AND MAIN RESULTS: The intratidal compliance-volume curve was determined with the slice method for each PEEP level. Concurrently, pulmonary gas exchange was assessed by the multiple inert gas elimination technique. At a PEEP of 0-1 cm H2O, the intratidal compliance-volume curve was formed a bow with downward concavity. At a PEEP of 2 cm H2O, concavity was minimal or compliance was almost constant, whereas higher PEEP levels (3-4 cm H2O) resulted in a decrease of compliance within tidal inflation. Pulmonary gas exchange did not differ between PEEP levels of of 0, 1, and 2 cm H2O. Pulmonary shunt was lowest and perfusion of alveoli with a normal ventilation-perfusion was highest at a PEEP of 3-4 cm H2O. Deadspace ventilation did not change significantly but tended to increase with PEEP. CONCLUSIONS: An increase of compliance at the very beginning of tidal inflation was associated with impaired pulmonary gas exchange, indicating insufficient alveolar recruitment by the PEEP level. Consequently, the lowest PEEP level preventing alveolar atelectasis could be detected by analyzing the course of compliance within tidal volume without the need for total lung inflation.

Extracorporeal membrane oxygenation: a ten-year experience.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy used for severe acute respiratory distress syndrome (ARDS). We present outcome, clinical parameters, and complications in a cohort of 245 ARDS patients of whom 62 were treated with ECMO. METHODS: Data of all ARDS patients were prospectively collected between 1991 and 1999. Outcome and clinical parameters of patients treated with and without ECMO were evaluated. RESULTS: One hundred thirty-eight patients were referred from other hospitals, 107 were primarily located in our hospital. About one fourth of these patients were treated with ECMO. The survival rate was 55% in ECMO patients and 61% in non-ECMO patients. CONCLUSIONS: ECMO is a therapeutic option for patients with severe ARDS, likely to increase survival. However, a randomized controlled study proving its benefit is still awaited. Until the development of a causal or otherwise superior therapy ECMO should be used in selected patients.

Breathing pattern associated with respiratory comfort during automatic tube compensation and pressure support ventilation in normal subjects.

BACKGROUND: Automatic tube compensation (ATC) is a new option to support spontaneously breathing tracheally intubated patients. We have previously demonstrated an increased respiratory comfort compared to pressure support ventilation (PSV) in volunteers. Here we characterized the breathing pattern during ATC associated with respiratory comfort in comparison to PSV. Furthermore, we studied whether ATC can be substituted by a simple modification of PSV. METHODS: We exposed 10 volunteers breathing through a 7.5 mm endotracheal tube via mouthpiece to PSV with 1) immediate and 2) delayed pressure rise and to 3) ATC. Immediate changes of the respiratory pattern after mode shifts were analyzed in detail. Furthermore, the volunteers were instructed to indicate changes in comfort after transitions between these modes as increased, unchanged, or decreased. RESULTS: Decreased comfort was associated with a substantial increase of tidal volume, minute ventilation, gas flow, and pressure. No differences in respiratory comfort were perceived between immediate and delayed pressure rise during PSV. CONCLUSION: PSV resulted in excessive tidal volumes and airflow, which was perceived as discomfort. This cannot be avoided by a delayed pressure rise but can be by the more comfortable ATC. ATC seems to adapt better to the ventilatory demand than PSV.

Unintended inhalation of nitric oxide by contamination of compressed air: physiologic effects and interference with intended nitric oxide inhalation in acute lung injury.

BACKGROUND: Compressed air from a hospital's central gas supply may contain nitric oxide as a result of air pollution. Inhaled nitric oxide may increase arterial oxygen tension and decrease pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. Therefore, the authors wanted to determine whether unintentional nitric oxide inhalation by contamination of compressed air influences arterial oxygen tension and pulmonary vascular resistance and interferes with the therapeutic use of nitric oxide. METHODS: Nitric oxide concentrations in the compressed air of a university hospital were measured continuously by chemiluminescence during two periods (4 and 2 weeks). The effects of unintended nitric oxide inhalation on arterial oxygen tension (n = 15) and on pulmonary vascular resistance (n = 9) were measured in patients with acute lung injury and acute respiratory distress syndrome by changing the source of compressed air of the ventilator from the hospital's central gas supply to a nitric oxide-free gas tank containing compressed air. In five of these patients, the effects of an additional inhalation of 5 ppm nitric oxide were evaluated. RESULTS: During working days, compressed air of the hospital's central gas supply contained clinically effective nitric oxide concentrations (> 80 parts per billion) during 40% of the time. Change to gas tank-supplied nitric oxide-free compressed air decreased the arterial oxygen tension by 10% and increased pulmonary vascular resistance by 13%. The addition of 5 ppm nitric oxide had a minimal effect on arterial oxygen tension and pulmonary vascular resistance when added to hospital-supplied compressed air but improved both when added to tank-supplied compressed air. CONCLUSIONS: Unintended inhalation of nitric oxide increases arterial oxygen tension and decreases pulmonary vascular resistance in patients with acute lung injury and acute respiratory distress syndrome. The unintended nitric oxide inhalation interferes with the therapeutic use of nitric oxide.

The Traveling Shutter Wave analyses non-linear compliance during mechanical ventilation.

Mechanical ventilation is an important, often life-saving component of modern intensive care medicine. However, it may further aggravate pulmonary pathology by endinspiratory overdistension of the alveoli or by their endexpiratory collapse. To prevent both the ventilator may be adjusted based on the slope of the pressure-volume curve, named as compliance, which is often determined by a stepwise inflation of the lungs. This maneuver gained no widespread clinical acceptance because of being cumbersome and invasive. Therefore, we developed a modification of the well known interrupter technique - the Traveling Shutter Wave. A wave of short-term (300 ms) occlusions "travels" over the tidal volume range. Differential compliance is calculated by division of volume and pressure differences between two adjacent occlusion maneuvers. The technique is well suited for the clinical setting because the ventilatory pattern does not need to be changed. This manuscript describes the realization of the Traveling Shutter Wave as well as its application in two patients.

Method for analysis of exhaled air by microwave energy desorption coupled with gas chromatography-flame ionization detection-mass spectrometry.

A method for chemical analysis of volatile constituents in exhaled air of mechanically ventilated patients is described. Exhaled substances are adsorbed and concentrated onto activated charcoal, desorbed by microwave energy and transferred into a gas chromatograph for separation without prior cryofocusing. Substances are identified by flame ionisation detection and mass spectrometry. This method yields reproducible results and is well suited for clinical studies.

Application of a new method for analysis of exhaled gas in critically ill patients.

OBJECTIVE: Application of a new method for analysis of exhaled gas in critically ill patients. DESIGN: Open study. SETTING: Surgical intensive care unit of an university hospital. PATIENTS: Thirty-seven consecutive, critically ill, mechanically ventilated patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Chemical analysis of the patient's exhaled gas was based upon substance adsorption and concentration onto activated charcoal, microwave desorption and gas chromatographic separation. Patients with acute respiratory distress syndrome (ARDS) exhaled less isoprene than those without ARDS [9.8 (8.2-21.6) vs 21.8 (13.9-41.4) nmol/m2 per min [median (95% confidence interval)], p = 0.04]. In patients who developed pulmonary infection, pentane elimination increased from 0.4 (0.0-5.4) to 2.7 (0.6-6.1, p = 0.05) nmol/m2 per min and isoprene elimination decreased from 5.2 (0-33) to 5.0 (0-17, p = 0.05) nmol/m2 per min, resulting in a significant increase in pentane/isoprene ratio from 0.1 (0-0.3) to 0.4 (0-15, p = 0.007) when compared to patients without pulmonary infection. CONCLUSIONS: The new method allows quantitative analysis of human gas samples with low substance concentrations and is well suited for clinical studies which involve the investigation of metabolic processes in the lung and the body.

Effect of different doses of inhaled nitric oxide on pulmonary capillary pressure and on longitudinal distribution of pulmonary vascular resistance in ARDS.

Inhaled nitric oxide lowers pulmonary capillary pressure (PCP) in animals and in patients with acute respiratory distress syndrome (ARDS). A dose-response relationship in patients with ARDS has not yet been established. Therefore, we studied the effects of four concentrations of nitric oxide (1, 10, 20 and 40 volumes per million (vpm)) in random order, on PCP in 19 patients with ARDS. PCP was estimated by visual analysis of the pressure decay curve after balloon inflation of the pulmonary artery catheter. Haemodynamic and gas exchange variables were measured at each nitric oxide concentration. Patients were classified as responders when PCP decreased by at least 2 mm Hg after nitric oxide 20 vpm. In responders (n = 8), nitric oxide decreased PCP and post-capillary vascular resistance dose-dependently and changed longitudinal distribution of pulmonary vascular resistance with a maximum effect at 20 vpm. In non-responders (n = 11), PCP did not change. In both groups, the nitric oxide-induced decrease in pre-capillary vascular resistance was small with a maximum effect at 1 vpm. In ARDS, vasodilatation of pre-capillary vessels is achieved at low concentrations of nitric oxide, whereas the effect of nitric oxide on postcapillary vessels is variable. Higher concentrations may be required for optimal post-capillary vasodilatation in a subgroup of ARDS patients.

Differential cytokine production in stimulated blood cultures from intensive care patients with bacterial infections.

Mice infected with bacteria develop an interferon-gamma (IFN-gamma) dependent hypersensitivity to lipopolysaccharide (LPS) and other bacterial components. The broader aim of this study is to find out whether such hypersensitivity also occurs in patients suffering from bacterial infections. The capacity of stimulated peripheral blood cells from infected, intensive-care patients to produce cytokines (IFN-gamma, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6)) was compared to that of healthy donors. Culturing of the cells was carried out preferentially in whole blood diluted 1:3. Whole blood cultures (WBC) were stimulated with lipopolysaccharide (LPS), whole killed Salmonella typhimurium and Staphylococcus aureus and concanavalin A (ConA), and the cytokine production was determined. Two main findings emerged from this study: The IFN-gamma production by WBC of patients was, compared to healthy donors, markedly suppressed, regardless of stimulus used. Further, patients' WBC exhibited a suppressed TNF-alpha production after stimulation with LPS. Surprisingly, following stimulation with bacteria (S. typhimurium and S. aureus) an elevated TNF-alpha and IL-6 response was obtained. Thus, in severely infected patients the cytokine responses of peripheral blood cells to LPS may be suppressed, while the response to other bacterial components is enhanced.

Hypoxic pulmonary vasoconstriction in nonventilated lung areas contributes to differences in hemodynamic and gas exchange responses to inhalation of nitric oxide.

BACKGROUND: Enhancement of hypoxic pulmonary vasoconstriction (HPV) in nonventilated lung areas by almitrine increases the respiratory response to inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). Therefore the authors hypothesized that inhibition of HPV in nonventilated lung areas decreases the respiratory effects of NO. METHODS: Eleven patients with severe ARDS treated by venovenous extracorporeal lung assist were studied. Patients' lungs were ventilated at a fraction of inspired oxygen (F[I(O2)]) of 1.0. By varying extracorporeal blood flow, mixed venous oxygen tension (P[O2]; partial oxygen pressure in mixed venous blood [PV(O2)]) was adjusted randomly to four levels (means, 47, 54, 64 and 84 mmHg). Extracorporeal gas flow was adjusted to prevent changes in mixed venous carbon dioxide tension [PV(CO2)]). Hemodynamic and gas exchange variables were measured at each level before, during, and after 15 ppm NO. RESULTS: Increasing PV(O2) from 47 to 84 mmHg resulted in a progressive decrease in lung perfusion pressure (PAP-PAWP; P < 0.05) and pulmnonary vascular resistance index (PVRI; P < 0.05) and in an increase in intrapulmonary shunt (Q[S]/Q[T]; P < 0.05). PV(CO2) and cardiac index did not change. Whereas the NO-induced reduction in PAP-PAWP was smaller at high PV(O2), NO-induced decrease in Q(S)/Q(T) was independent of baseline PV(O2). In response to NO, arterial P(O2) increased more and arterial oxygen saturation increased less at high compared with low PV(O2). CONCLUSION: In patients with ARDS, HPV in nonventilated lung areas modifies the hemodynamic and respiratory response to NO. The stronger the HPV in nonventilated lung areas the more pronounced is the NO-induced decrease in PAP-PAWP. In contrast, the NO-induced decrease in Q(S)/Q(T) is independent of PV(O2) over a wide range of PV(O2) levels. The effect of NO on the arterial oxygen tension varies with the level of PV(O2) by virtue of its location on the oxygen dissociation curve.

[Double isotope albumin flux measurement: diagnosis and therapeutic monitoring of acute lung injury]. / Doppelisotopen-Albuminfluxmessung: Diagnose und Therapiemonitoring des Acute Lung Injury.

PURPOSE: Acute Lung Injury (ALI) is a clinical condition which is associated with a high lethality. It is characterized by an increased pulmonary capillary permeability and non-cardiogenic pulmonary edema. This study was designed to answer the question whether double isotope albumin-flux measurement is a useful tool both for diagnosis of increased pulmonary capillary permeability and for monitoring therapeutic interventions (nitric oxide (NO) inhalation). METHOD: In 12 patients with clinical signs of ALI, transvascular albumin-flux was measured by a double radioisotope technique before, during and after NO inhalation. 99mTc labeled albumin and 51Cr labeled autologous erythrocytes were used as tracer. The radioactivity of both radiopharmaceuticals was measured externally over the right lung by a radiation probe and simultaneously in arterial blood. For quantification of transvascular albumin-flux Normalized Index (NI) and Normalized Slope Index (NSI) were calculated. Furthermore, pulmonal vascular pressures and other physiological parameters were recorded. RESULTS: All 12 patients showed markedly increased NSI before inhalation of NO. NSI decreased from 0.0074 +/- 0.0046 min-1 without nitric oxide to -0.0051 +/- 0.0041 min-1 during nitric oxide and increased to 0.0046 +/- 0.0111 min-1 after nitric oxide. The decrease of the NSI correlated well with decrease of venous pulmonary resistance during inhalation of NO. CONCLUSION: Inhalation of NO reduces transvascular albumin-flux in patients with ALI. Double isotope albumin-flux measurement enables diagnosis of increased capillary permeability as well as monitoring therapeutic interventions.

Large increase in cardiac output in a patient with ARDS and acute right heart failure during inhalation of nitric oxide.

BACKGROUND: Inhaled nitric oxide (NO), a selective pulmonary vasodilator, reduces pulmonary artery pressure in patients with acute respiratory distress syndrome (ARDS). In spite of the reduction of right ventricular afterload, the effect of NO on cardiac output remains unclear. METHODS: A patient with ARDS and echocardiographically determined severe acute right heart failure was treated with increasing concentrations of inhaled nitric oxide (NO). Haemodynamic and gas exchange variables were determined for each concentration of NO. NO treatment was continued for 3 days. RESULTS: During initial right heart failure, administration of NO resulted in a large increase (32%) in cardiac output in a dose-dependent manner. When right ventricular function had improved, inhalation of NO did not increase cardiac output. CONCLUSION: Our observations suggest that inhalation of NO is likely to increase cardiac output in ARDS when severe acute right heart failure is present.