Gender differences and influenza-associated mortality in hospitalized influenza A patients during the 2018/19 season.

BACKGROUND: In this study we analyzed gender differences in the clinical presentation of patients with molecular confirmed influenza A. Additionally, we tried to identify predictors of influenza-associated mortality. MATERIALS/METHODS: In this prospective observational multi-center-study we included all influenza-positive patients ≥ 18 years who were hospitalized and treated on flu-isolation-wards in three hospitals in Vienna during the 2018/19 influenza season. Diagnoses were made via Cobas® Liat® POCT. RESULTS: 490 Patients (48.8% female) tested positive for influenza A. Female patients were older (median age 76 years vs. 70 years, p < 0.001). Male patients had a higher rate of chronic liver disease in history (8.8% vs. 2.9%, p = 0.006), myositis (11.7% vs. 3.1%, p < 0.001) and ICU admissions (9.6% vs. 4.6%, p = 0.03). The in-hospital mortality rate was 4.3% and increased to 9.5% during the 90-day follow-up period. Female patients > 75 years had a significantly higher in-hospital mortality rate than ≤ 75-year-old females (9.2% vs. 1.7%, p = 0.019). This effect was not observed in male patients (5.4% vs. 1.9%, p = ns). Age > 75 years (OR 5.49, 95% CI 1.10-27.43), acute heart failure (OR 3.56, 95% CI 1.03-12.05) and ICU admission (OR 6.1, 95% CI 0.98-37.91) were predictors for in-hospital mortality for female patients, while any malignancy (OR 9.4, 95% CI 1.90-46.54) and ICU admission (OR 7.05, 95% CI 1.44-34.55) were predictors in male patients. CONCLUSIONS: Gender is associated with differences in clinical presentation and complications of influenza A virus infection. Women with acute heart failure or aged > 75 years have an increased risk of influenza associated in-hospital mortality, while ICU admission and any malignancy are predictors for male patients. Mortality rates in patients > 75 years are 5-10 times higher compared to their non-hospitalized influenza-negative Austrian counterparts.

Normal saline versus a balanced crystalloid for goal-directed perioperative fluid therapy in major abdominal surgery: a double-blind randomised controlled study.

BACKGROUND: This double-blind randomised controlled trial investigated whether normal saline or a balanced crystalloid has distinct effects on vasopressor use in patients undergoing major abdominal surgery. METHODS: Patients received either normal saline 0.9% or an acetate-buffered crystalloid for intraoperative volume replacement in a goal-directed fashion. The primary outcome was need for vasopressors; the secondary outcomes were the total dose of catecholamines, total perioperative fluid, and unplanned intensive care admissions. RESULTS: This study was terminated early for safety reasons. A total of 60 out of the planned 240 patients were randomized. Thirty patients received normal saline and 30 patients received the balanced crystalloid, with a total volume of 3427 (2732-4130) ml and 3144 (1673-4926), respectively. The normal-saline group developed hyperchloraemic metabolic acidosis. More patients needed vasopressors for circulatory support in the normal-saline group compared with the buffered crystalloid group (97% vs 67%, respectively; P=0.033). The median weight and anaesthesia duration-adjusted dose of norepinephrine were 0.11 (0.00-0.45) ng kg-1 min-1 and 0.00 (0.00-0.00) kg-1 min-1 in the normal-saline and balanced-crystalloid groups, respectively (P=0.003). Cox regression revealed that the need for vasopressors was related to a high volume of administered fluid, normal-saline resuscitation, and lower mean arterial blood pressure. There was no difference between the groups in total perioperative fluid and unplanned intensive-care-unit admissions. Between-group differences in the duration of anaesthesia did not influence the necessity for a vasopressor. CONCLUSIONS: Compared with patients receiving a balanced crystalloid, normal saline in patients undergoing major abdominal surgery was associated with an increased need for vasopressor support. This should be interpreted in view of the large volume of fluid resuscitation and the small sample size because of the preliminary termination of the study. CLINICAL TRIAL REGISTRATION: EudraCT 2014-004867-19, NCT 02414555.

[Pain, agitation and delirium in acute respiratory failure]. / Schmerz, Unruhe und Delir bei akuter respiratorischer Insuffizienz.

Avoiding pain, agitation and delirium as well as avoiding unnecessary deep sedation is a powerful yet challenging strategy in critical care medicine. A number of interactions between cerebral function and respiratory function should be regarded in patients with respiratory failure and mechanical ventilation. A cooperative sedation strategy (i.e. patient is awake and free of pain and delirium) is feasible in many patients requiring invasive mechanical ventilation. Especially patients with mild acute respiratory distress syndrome (ARDS) seem to benefit from preserved spontaneous breathing. While completely disabling spontaneous ventilation with or without neuromuscular blockade is not a standard strategy in ARDS, it might be temporarily required in patients with severe ARDS, who have substantial dyssynchrony or persistent hypoxaemia. Since pain, agitation and delirium compromise respiratory function they should also be regarded during noninvasive ventilation and during ventilator weaning. Pharmacological sedation can have favourable effects in these situations, but should not be given routinely or uncritically.

Impact of proton pump inhibitor use on magnesium homoeostasis: a cross-sectional study in a tertiary emergency department.

BACKGROUND: To date, the use of proton pump inhibitors (PPIs) has been associated with a low risk of hypomagnesaemia and associated adverse outcomes. We hypothesised that a better risk estimate could be derived from a large cohort of outpatients admitted to a tertiary emergency department (ED). METHODS: A cross-sectional study was performed in 5118 patients who had measurements of serum magnesium taken on admission to a large tertiary care ED between January 2009 and December 2010. Hypomagnesaemia was defined as a serum magnesium concentration < 0.75 mmol/l. Demographical data, serum electrolyte values, data on medication, comorbidities and outcome with regard to length of hospital stay and mortality were analysed. RESULTS: Serum magnesium was normally distributed where upon 1246 patients (24%) were hypomagnesaemic. These patients had a higher prevalence of out-of-hospital PPI use and diuretic use when compared with patients with magnesium levels > 0.75 mmol/l (both p < 0.0001). In multivariable regression analyses adjusted for PPIs, diuretics, renal function and the Charlson comorbidity index score, the association between use of PPIs and risk for hypomagnesaemia remained significant (OR = 2.1; 95% CI: 1.54-2.85). While mortality was not directly related to low magnesium levels (p = 0.67), the length of hospitalisation was prolonged in these patients even after adjustment for underlying comorbid conditions (p < 0.0001). CONCLUSION: Use of PPIs predisposes patients to hypomagnesaemia and such to prolonged hospitalisation irrespective of the underlying morbidity, posing a critical concern.

[Difficult to wean patients]. / Der schwer entwöhnbare Patient.

Approximately 10% of patients with mechanical ventilation experience prolonged weaning and also have an increased morbidity and mortality. Once spontaneous breathing trials have failed the organ systems responsible should be identified. This can be accomplished during the spontaneous breathing trial using clinical examination, measurement of blood gases, echocardiography and imaging techniques. Specific patterns allow the diagnosis of pathological respiratory mechanisms, weak ventilatory muscles, heart failure, myocardial ischemia and psychiatric problems. Respiratory and cardiac limitations of weaning can be overcome by reducing the ventilatory load, training of the ventilatory muscles and reducing cardiac workload. A cooperative sedation strategy as well as an early start of weaning and rehabilitation can prevent prolonged weaning in critically ill patients.

[Non-invasive mechanical ventilation in COPD]. / Nichtinvasive Beatmung bei COPD.

Non-invasive mechanical ventilation is the preferred method for the treatment of acute respiratory failure in patients with chronic obstructive pulmonary disease (COPD). Primary contraindications and stopping criteria must be regarded to avoid delaying endotracheal intubation. The primary interface is usually a nasal-oral mask. Cautious sedation can facilitate non-invasive ventilation in some patients. Under certain circumstances non-invasive ventilation may enable successful extubation in COPD patients with prolonged weaning. COPD patients can also benefit from preventive non-invasive ventilation in order to avoid re-intubation after a planned extubation. Domiciliary nocturnal non-invasive ventilation is an option for some patients with COPD in chronic hypercapnic respiratory failure. This treatment should be established in a specialised unit.

Incidence and outcome of weaning from mechanical ventilation according to new categories.

Weaning from mechanical ventilation was categorised as simple, difficult or prolonged by an international task force of the American Thoracic Society/European Respiratory Society/European Society of Intensive Care Medicine/Society of Critical Care Medicine/Sociéte de Réanimation de Langue Française in 2007. This new classification has not been tested in clinical practice. The objective of the present study was to determine the incidence and outcome of weaning according to the new categories. We included medical and surgical patients who required mechanical ventilation in a prospective, multicentre, 6-month cohort study. From an initial cohort of 510 patients, 257 intubated patients started weaning. Of these patients, the cumulative incidences of simple, difficult, and prolonged weaning were 152 (59%), 68 (26%) and 37 (14%), respectively. Hospital mortality was increased in patients with prolonged (32%) but not difficult (9%) weaning in comparison with those with simple weaning (13%), overall p = 0.0205. In a multivariate logistic regression model, prolonged but not difficult weaning was associated with an increased risk of death. Ventilator-free days and intensive care unit (ICU)-free days were decreased in both difficult and prolonged weaning. In conclusion, the new weaning category prolonged weaning is associated with increased mortality and morbidity in the ICU. The new category difficult to wean was associated with increased morbidity, but not mortality.

Unusual microbes in asthma exacerbation: Alcaligenes xylosoxidans and Leishmania.

Asthma is a chronic inflammatory condition characterised by a variable degree of airflow limitation. Exacerbations during the course of asthma often occur due to environmental factors or infectious, mostly viral, aetiology. The present study reports the case of a 61-yr-old male with severe asthma hospitalised due to increasing respiratory distress. Since recovery was delayed despite anti-obstructive/anti-inflammatory and antibiotic therapy, further diagnostic procedures, including bronchoscopy, were performed in order to attempt to identify the cause of the worsening respiratory condition. The surprising finding consisted of a rare coincidence of concomitant infection with the bacterial pathogen Alcaligenes xylosoxidans, grown from bronchoalveolar lavage fluid, and the protozoan parasite Leishmania spp., revealed by histopathological examination of bronchial mucosal biopsy specimens. This is the first report of an isolated bronchial mucosal involvement of Leishmania in an HIV-negative asthma patient following brief exposure in Leishmania-endemic regions. Further, to the best of the present authors' knowledge, this represents the first description of A. xylosoxidans in asthma, although it is questionable whether it was an infection or colonisation. The present observation identifies previously unreported microbial pathogens associated with asthma exacerbation. Further, the report highlights the importance of obtaining a thorough travel history and applying invasive diagnostic procedures in circumstances of treatment failure, even under unfavourable conditions.

Acute phase proteins do not account for unmeasured anions in critical illness.

BACKGROUND: The increasingly recognized prognostic impact of the strong ion gap in critical illness is in contrast to its largely unknown chemical nature. Experimental and clinical evidence suggest that acute phase proteins might account for elevation of the strong ion gap. The hypothesis of this investigation was that acute phase proteins account for strong ion gap in critically ill patients. MATERIALS AND METHODS: The charges of the two acute phase proteins C-reactive protein and fibrinogen were estimated by a computer model. Additionally, 142 patients admitted to a medical intensive care unit of a university hospital were studied prospectively during a six month period. Serial daily observations were recorded and classified according to the systemic inflammatory state. The acute phase proteins C-reactive protein and fibrinogen were measured and the strong ion gap was calculated from the measured acid-base variables. RESULTS: The approximated mean charges of C-reactive protein and fibrinogen at a pH of 7.4 are -4.0 and -13.6 per molecule, respectively. Therefore, their negative charge is too small to explain the elevated strong ion gap even during a substantial increase of C-reactive protein and fibrinogen due to an acute-phase reaction. Moreover, C-reactive protein did not correlate with the strong ion gap when partialized for creatinine (R = 0.02, P = 0.567). Fibrinogen did not correlate with the strong ion gap. Creatinine correlated with the strong ion gap (R = 0.42, P < 0.001). Neither systemic inflammatory state nor increasing C-reactive protein levels were associated with an increasing strong ion gap. CONCLUSION: Acute phase proteins do not account for an elevated strong ion gap in critically ill patients.

Correlation of calculated indices of insulin resistance (QUICKI and HOMA) with the euglycaemic hyperinsulinaemic clamp technique for evaluating insulin resistance in critically ill patients.

BACKGROUND AND OBJECTIVE: Insulin resistance is frequently observed in critical illness. It can be quantified by the expensive and time-consuming euglycaemic hyperinsulinaemic clamp technique (M-value) and calculated indices of insulin resistance (Quantitative Insulin Sensitivity Check Index; QUICKI and Homeostasis Model Assessment; HOMA) with lower costs and efforts. We performed an observational study to assess the reliability of QUICKI and HOMA to evaluate insulin resistance in critically ill patients compared with the current gold standard method, the euglycaemic hyperinsulinaemic clamp technique. METHODS: Insulin resistance was measured in 30 critically ill medical patients by the euglycaemic hyperinsulinaemic clamp technique (M-value) as well as calculated using QUICKI and HOMA. Correlations between the M-values as well as QUICKI and HOMA were assessed by means of the Pearson's correlation coefficient. RESULTS: M-value, QUICKI and HOMA indicated insulin resistance in all 30 patients. However, both indices QUICKI and HOMA did not correlate with the M-values in our patients (r2 = 0.008 and 0.0005, respectively). A significant negative correlation was found between the M-value and the severity of illness assessed by the APACHE (Acute Physiology and Chronic Health Evaluation) III score (r2 = 0.16; P < 0.05). In contrast, neither HOMA nor QUICKI correlated with the APACHE III score (r2 = 0.034 and 0.033, respectively). CONCLUSIONS: Although QUICKI and HOMA indicated insulin resistance in the critically ill medical patients, both indices did not correlate with the M-value. Therefore, the euglycaemic hyperinsulinaemic clamp technique remains the gold standard for estimating insulin resistance in critically ill patients.

Changes of serum chloride and metabolic acid-base state in critical illness.

Alterations of electrolytes and albumin cause metabolic acid-base disorders. It is unclear, however, to what degree these plasma components affect the overall metabolic acid-base state in the course of critical illness. We performed serial analyses of the metabolic acid-base state in 30 critically ill patients over the course of 1 week. We applied a physical-chemical acid-base model and used a linear regression model to determine the influence of sodium, chloride, unmeasured anions and albumin on the net metabolic acid-base state. Progressive hypochloraemia was identified as the main cause of developing metabolic alkalosis. Changes in serum chloride and unmeasured anions were responsible for changes of 41% and 22% in the metabolic acid-base state, respectively. Sodium and albumin played a minor role. In conclusion, chloride is the major determinant of metabolic acid-base state in critical illness.

Electrophysiological assessment of the afferent sensory pathway in cardiac arrest survivors.

BACKGROUND: Hypoxic-ischaemic brain damage in cardiac arrest survivors is global, but postmortem histology could identify parts of the brain that are selectively vulnerable to ischaemia, comprising the thalamus and cortex. We hypothesized that hypoxic-ischaemic brain damage increases along the afferent sensory pathway with a stepwise decrease of detectable somatosensory evoked potential peaks. METHODS: Somatosensory evoked potentials were recorded within 72 h after cardiac arrest in 305 comatose patients after cardiopulmonary resuscitation. We measured the short latency SEP peaks N9, P15, N20, P25 (reflecting the peripheral-thalamo-cortical pathway) and the long latency SEP peaks N35 and N70 (reflecting complex cortico-cortical interactions). Patients with a Cerebral Performance Category score > 2 at 1 year were defined as patients with hypoxic-ischaemic brain damage. RESULTS: Patients with hypoxic-ischaemic brain damage (n = 232) showed a statistically significant decrease of detectable peaks (P < 0.05) along the thalamo-cortical afferent pathway: N13, P15, N20, P25 and N70 peaks were detectable in 99%, 63%, 59%, 55% and 44% patients, respectively. In patients without hypoxic-ischaemic brain damage (n = 73) the N13, P15, N20, P25 peaks were detectable in all, and the N35 and N70 peaks in 98%. Furthermore, in patients with hypoxic-ischaemic brain damage and detectable SEP peaks, P15, N20, P25, N35 and N70, peak latencies were prolonged (P < 0.05) and N20 and N70 amplitudes were decreased (P < 0.05) compared with patients without hypoxic-ischaemic brain damage. CONCLUSION: Extent of hypoxic-ischaemic brain damage in cardiac arrest survivors increases along the afferent sensory pathway, with pronounced vulnerability of thalamic and cortical brain regions.

Time-dependency of sensory evoked potentials in comatose cardiac arrest survivors.

OBJECTIVE: To assess the validity of early sensory evoked potential (SEP) recording for reliable outcome prediction in comatose cardiac arrest survivors within 48 h after restoration of spontaneous circulation (ROSC). DESIGN AND SETTING: Prospective cohort study in a medical intensive care unit of a university hospital. PATIENTS: Twenty-five comatose, mechanically ventilated patients following cardiopulmonary resuscitation MEASUREMENTS AND RESULTS: Median nerve short- and long-latency SEP were recorded 4, 12, 24, and 48 h after ROSC. Cortical N20 peak latency and cervicomedullary conduction time decreased (improved) significantly between 4, 12, and 24 h after resuscitation in 22 of the enrolled patients. There was no further change in short-latency SEP at 48 h. The cortical N70 peak was initially detectable in seven patients. The number of patients with increased N70 peak increased to 11 at 12 h and 14 at 24 h; there was no further change at 48 h. Specificity of the N70 peak latency (critical cutoff 130 ms) increased from 0.43 at 4 h to 1.0 at 24 h after ROSC. Sensitivity decreased from 1.0 at 4 h to 0.83 at 24 h after ROSC. CONCLUSION: Within 24 h after ROSC there was a significant improvement in SEP. Therefore we recommend allowing a period of at least 24 h after cardiopulmonary resuscitation for obtaining a reliable prognosis based on SEP.