Abnormalities of Coagulation and Fibrinolysis Assessed by Thromboelastometry in an Endotoxic Shock Model in Piglets Treated with Nitric Oxide and Hydrocortisone.

This is an animal model study to investigate changes in hemostasis during endotoxemic shock and to determine whether the combination of inhaled nitric oxide (iNO) + intravenous hydrocortisone had an effect on clot formation and fibrinolysis. iNO selectively decreases pulmonary artery pressure, without affecting cardiac index or systemic vascular resistance; however, the results of studies on the possible consequences of iNO administration on coagulation are inconsistent and require further research. Thirty-four piglets were included. Administering endotoxin caused severe hypodynamic shock. Half of the animals received iNO (30 ppm) + hydrocortisone, starting 3 h after endotoxin infusion and continuing to the end of the study. All animals developed coagulation disorders, manifested by a tendency to hypocoagulation; at the same time, fibrinolysis was impaired. Coagulation and fibrinolysis disorders persisted after endotoxin infusion was discontinued, with worse severity in the animals that died before the study was terminated. Administering iNO + hydrocortisone did not cause further changes in coagulation and fibrinolysis parameters, either during or after the endotoxin challenge, suggesting that potential therapeutic interventions with iNO to lower pulmonary arterial pressure will not affect hemostasis.

The Impact of Body Mass Index on In-Hospital Mortality in Post-Cardiac-Arrest Patients-Does Sex Matter?

BACKGROUND: A number of factors influence mortality in post-cardiac-arrest (CA) patients, nutritional status being one of them. The aim of this study was to assess whether there are sex differences in the prognostic impact of BMI, as calculated on admission to an intensive care unit, on in-hospital mortality in sudden cardiac arrest (SCA) survivors. METHODS: We carried out a retrospective analysis of data of 129 post-cardiac-arrest patients with return of spontaneous circulation (ROSC) admitted to the Intensive Care Unit (ICU) of the University Teaching Hospital in Wroclaw between 2017 and 2022. RESULTS: Female patients were significantly older than male patients (68.62 ± 14.77 vs. 62.7 ± 13.95). The results of univariable logistic regression analysis showed that BMI was not associated with the odds of in-hospital death in either male or female patients. In an age-adjusted model, age was an independent predictor of the odds of in-hospital death only in male patients (OR = 1.034). In our final multiple logistic regression model, adjusted for the remaining variables, none of the traits analysed were a significant independent predictor of the odds of in-hospital death in female patients, whereas an initial rhythm of ventricular fibrillation or pulseless ventricular tachycardia (VF/pVT) was an independent predictor of the odds of in-hospital death in male patients (OR = 0.247). CONCLUSIONS: BMI on admission to ICU is not a predictor of the odds of in-hospital death in either male or female SCA survivors.

Effect of low-dose hydrocortisone and inhaled nitric oxide on inflammatory mediators and local pulmonary metalloproteinases activity in LPS-induced sepsis in piglets.

Hospital mortality in sepsis varies between 30-45%. It has been shown that administration of inhaled nitric oxide (iNO) and intravenous corticosteroid in a porcine endotoxemia model attenuated the systemic inflammatory response. We explored the anti-inflammatory effect of a double-treatment strategy (iNO + low-dose steroid) on the lungs in a long-term porcine endotoxic shock model. As metalloproteinases (MMPs) are involved in the initiation of multiple organ dysfunction in septic shock, we evaluated the influence of this combination therapy on MMP2 and MMP9 activity and proIL-1ß maturation. A shock-like condition was established in 23 animals by continuous infusion of E. coli lipopolysaccharide (LPS) for 10 h. Then the animals were observed for 10 h. Twelve pigs received iNO and hydrocortisone (iNO treatment started 3 h after the initial LPS infusion and continued until the end of the experiment). Eleven pigs were controls. Pigs treated with iNO and hydrocortisone displayed less inflammatory infiltrates in the lungs than the controls and a lower level of IL-1ß. The proMMP2 was significantly decreased in the iNO and hydrocortisone group. The amount of an active MMP9 (~ 60 kDa) was decreased in the iNO and hydrocortisone group. Total gelatinolytic activity was lower in the iNO and hydrocortisone group. Reduced MMP activity was accompanied by a 2.5-fold decrease of the active IL-1ß form (17 kDa) in the pulmonary tissue of iNO combined with hydrocortisone exposed pigs. We demonstrated that in a porcine endotoxemia model the NO inhalation combined with intravenous hydrocortisone led to the attenuation of the inflammatory cascade induced by bacterial LPS. The decrease in pulmonary MMPs activities was accompanied by reduced proIL-1ß processing.

Do Body Mass Index and Nutritional Risk Score 2002 Influence the In-Hospital Mortality of Patients Following Cardiac Arrest?

BACKGROUND: Contemporarily, cardiac arrest (CA) remains one of the leading causes of death. Poor nutritional status can increase the post-CA mortality risk. The aim of this study was to determine the relationship between body mass index (BMI) and Nutritional Risk Score 2002 (NRS 2002) results and in-hospital mortality in patients admitted to the intensive care unit (ICU) after in-hospital and out-of-hospital cardiac arrest. METHODS: A retrospective study and analysis of medical records of 161 patients admitted to the ICU of the University Clinical Hospital in Wroclaw (Wroclaw, Poland) was conducted. RESULTS: No significant differences in body mass index (BMI) and nutritional risk score (NRS 2002) values were observed between non-survivors and survivors. Non-survivors had significantly lower albumin concentration (p = 0.017) and total cholesterol (TC) (p = 0.015). In multivariate analysis BMI and NRS 2002 scores were not, per se, associated with the in-hospital mortality defined as the odds of death (Model 1: p: 0.700, 0.430; Model 2: p: 0.576, 0.599). Univariate analysis revealed significant associations between the hazard ratio (HR) and TG (p ≈ 0.017, HR: 0.23) and hsCRP (p ≈ 0.018, HR: 0.34). In multivariate analysis, mortality risk over time was influenced by higher scores in parameters such as BMI (HR = 0.164; p = 0.048) and hsCRP (HR = 1.006, p = 0.002). CONCLUSIONS: BMI and NRS 2002, on their own (unconditionally - in the whole study group) did not alter the odds of mortality in patients admitted to the intensive care unit (ICU) after in-hospital and out-of-hospital cardiac arrest. The risk of in-hospital mortality (expressed as hazard ratio - the risk over the time period of the study) increased with an increase in BMI but not with NRS 2002.

Usefulness of C2HEST Score in Predicting Clinical Outcomes of COVID-19 in Heart Failure and Non-Heart-Failure Cohorts.

Background: Patients with heart failure represent a vulnerable population for COVID-19 and are prone to having worse prognoses and higher fatality rates. Still, the clinical course of the infection is dynamic, and complication occurrence in particular in patients with heart failure is fairly unpredictable. Considering that individual components of the C2HEST (C2: Coronary Artery Diseases (CAD)/Chronic obstructive pulmonary disease (COPD); H: Hypertension; E: Elderly (Age ≥ 75); S: Systolic HF; T: Thyroid disease) are parallel to COVID-19 mortality risk factors, we evaluate the predictive value of C2HEST score in patients with heart failure (HF) Material and Methods: The retrospective medical data analysis of 2184 COVID-19 patients hospitalized in the University Hospital in Wroclaw between February 2020 and June 2021 was the basis of the study. The measured outcomes included: in-hospital mortality, 3-month and 6-month all-cause-mortality, non-fatal end of hospitalization, and adverse in-hospital clinical events. Results: The heart failure cohort consists of 255 patients, while 1929 patients were assigned to the non-HF cohort. The in-hospital, 3-month, and 6-month mortality rates were highest in the HF cohort high-risk C2HEST stratum, reaching 38.61%, 53.96%, and 65.36%, respectively. In the non-HF cohort, in-hospital, 3-month, and 6-month mortalities were also highest in the high-risk C2HEST stratum and came to 26.39%, 52.78%, and 65.0%, respectively. An additional point in the C2HEST score increased the total death intensity in 10% of HF subjects (HR 1.100, 95% CI 0.968−1.250 p = 0.143) while in the non-HF cohort, the same value increased by 62.3% (HR 1.623, 95% CI 1.518−1.734 p < 0.0001). Conclusions: The C2HEST score risk in the HF cohort failed to show discriminatory performance in terms of mortality and other clinical adverse outcomes during hospitalization. C2HEST score in the non-HF cohort showed significantly better performance in terms of predicting in-hospital and 6-month mortality and other non-fatal clinical outcomes such as cardiovascular events (myocardial injury, acute heart failure, myocardial infarction, cardiogenic shock), pneumonia, sepsis, and acute renal injury.

Compartment-Specific Differences in the Activation of Monocyte Subpopulations Are Not Affected by Nitric Oxide and Glucocorticoid Treatment in a Model of Resuscitated Porcine Endotoxemic Shock.

Inhaled nitric oxide (iNO) remains one of the treatment modalities in shock, and in addition to its vasoactive properties, iNO exerts immunomodulatory effects. We used a porcine model of endotoxemia with shock resuscitation (control) and additional treatment with iNO and a steroid (treatment group). After 20 h, bone marrow (BM), peripheral blood (PB), and bronchoalveolar lavage fluid (BALF) were collected to analyze the immunophenotype and mitochondrial membrane potential (Δφ) in three subsets of monocytes. In both groups, SLA-DR expression decreased twofold on the circulating CD14+CD163+ and CD14−CD163+ monocytes, while it did not change on the CD14+CD163+. Δφ increased only in the CD14−CD163+ subpopulation (0.8 vs. 2.0, p < 0.001). The analysis of compartment-specific alterations showed that nearly 100% of BALF CD14+CD163+ and CD14−CD163+ monocytes expressed SLA-DR, and it was higher compared to PB (32% and 20%, p < 0.0001) and BM (93% and 67%, p < 0.001, respectively) counterparts. BALF CD14+CD163+ had a threefold higher Δφ than PB and BM monocytes, while the Δφ of the other subsets was highest in PB monocytes. We confirmed the compartmentalization of the monocyte response during endotoxemic shock, which highlights the importance of studying tissue-resident cells in addition to their circulating counterparts. The iNO/steroid treatment did not further impair monocyte fitness.

The Association between Nutritional Status and In-Hospital Mortality of COVID-19 in Critically-Ill Patients in the ICU.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has become one of the leading causes of death worldwide. The impact of poor nutritional status on increased mortality and prolonged ICU (intensive care unit) stay in critically ill patients is well-documented. This study aims to assess how nutritional status and BMI (body mass index) affected in-hospital mortality in critically ill COVID-19 patients Methods: We conducted a retrospective study and analysed medical records of 286 COVID-19 patients admitted to the intensive care unit of the University Clinical Hospital in Wroclaw (Poland). RESULTS: A total of 286 patients were analysed. In the sample group, 8% of patients who died had a BMI within the normal range, 46% were overweight, and 46% were obese. There was a statistically significantly higher death rate in men (73%) and those with BMIs between 25.0-29.9 (p = 0.011). Nonsurvivors had a statistically significantly higher HF (Heart Failure) rate (p = 0.037) and HT (hypertension) rate (p < 0.001). Furthermore, nonsurvivors were statistically significantly older (p < 0.001). The risk of death was higher in overweight patients (HR = 2.13; p = 0.038). Mortality was influenced by higher scores in parameters such as age (HR = 1.03; p = 0.001), NRS2002 (nutritional risk score, HR = 1.18; p = 0.019), PCT (procalcitonin, HR = 1.10; p < 0.001) and potassium level (HR = 1.40; p = 0.023). CONCLUSIONS: Being overweight in critically ill COVID-19 patients requiring invasive mechanical ventilation increases their risk of death significantly. Additional factors indicating a higher risk of death include the patient's age, high PCT, potassium levels, and NRS ≥ 3 measured at the time of admission to the ICU.

Platelet dysfunction in a large-animal model of endotoxic shock; effects of inhaled nitric oxide and low-dose steroid.

OBJECTIVE: The role of inhaled nitric oxide in the treatment of shock remains controversial and further translational research is needed. Long-term observation studies using a model of endotoxin-induced shock to assess the effect of inhaled nitric oxide on platelet aggregation have not yet been reported. APPROACH AND RESULTS: The tests were carried out in an animal model of shock in two 10-h periods. During the first 10 h, endotoxin was infused and the inhibition of platelet aggregation was evaluated; following the termination of endotoxin infusion, the restoration of platelet aggregation was assessed for 10 h. A total of 30 pigs were used (NO group, N = 14; control, N = 16). In the NO group, nitric oxide inhalation (30 ppm) was started 3 h after endotoxin infusion and continued until the end of the study. Treatment with NO selectively decreased pulmonary artery pressure at 4 (p = 0.002) and 8 h (p = 0.05) of the experiment as compared to the control. Endotoxin significantly reduced platelet aggregation, as indicated by the decreased activity of platelet receptors: ASPI, ADP, collagen, and TRAP during the experiment (p < 0.001). Endotoxin had no significant effect on changes in the response of the receptor after ristocetin stimulation. After stopping endotoxin infusion, a significant restoration of receptor activity was observed for collagen and TRAP, while ASPI and ADP remained partially depressed. Inhaled nitric oxide did not cause additional inhibition of platelet aggregation, either during or after endotoxin challenge. CONCLUSIONS: A profound reduction in platelet aggregation was observed during endotoxic shock. After stopping endotoxin infusion a restoration of platelet receptor activity was seen. The inhibition of platelet aggregation induced by endotoxin infusion was not intensified by nitric oxide, indicating there was no harmful effect of inhaled nitric oxide on platelet aggregation.

Pulmonary Vasodilation by Intravenous Infusion of Organic Mononitrites Of 1,2-Propanediol in Acute Pulmonary Hypertension Induced by Aortic Cross Clamping and Reperfusion: A Comparison With Nitroglycerin in Anesthetized Pigs.

INTRODUCTION: Suprarenal aortic cross clamping (SRACC) and reperfusion may cause acute pulmonary hypertension and multiple organ failure. HYPOTHESIS: The organic mononitrites of 1,2-propanediol (PDNO), an nitric oxide donor with a very short half-life, are a more efficient pulmonary vasodilator and attenuator of end-organ damage and inflammation without significant side effects compared with nitroglycerin and inorganic nitrite in a porcine SRACC model. METHODS: Anesthetized and instrumented domestic pigs were randomized to either of four IV infusions until the end of the experiment (n = 10 per group): saline (control), PDNO (45 nmol kg min), nitroglycerin (44 nmol kg min), or inorganic nitrite (a dose corresponding to PDNO). Thereafter, all animals were subjected to 90 min of SRACC and 10 h of reperfusion and protocolized resuscitation. Hemodynamic and respiratory variables as well as blood samples were collected and analysed. RESULTS: During reperfusion, mean pulmonary arterial pressure and pulmonary vascular resistance were significantly lower, and stroke volume was significantly higher in the PDNO group compared with the control, nitroglycerin, and inorganic nitrite groups. In parallel, mean arterial pressure, arterial oxygenation, and fraction of methaemoglobin were similar in all groups. The serum concentration of creatinine and tumor necrosis factor alpha were lower in the PDNO group compared with the control group during reperfusion. CONCLUSIONS: PDNO was an effective pulmonary vasodilator and appeared superior to nitroglycerin and inorganic nitrite, without causing significant systemic hypotension, impaired arterial oxygenation, or methaemoglobin formation in an animal model of SRACC and reperfusion. Also, PDNO may have kidney-protective effects and anti-inflammatory properties.

Organic mononitrites of 1,2-propanediol act as an effective NO-releasing vasodilator in pulmonary hypertension and exhibit no cross-tolerance with nitroglycerin in anesthetized pigs.

PURPOSE: Clinically available intravenous (IV) nitric oxide (NO) donor drugs such as nitroglycerin (GTN) cause systemic hypotension and/or tolerance development. In a porcine model, novel NO donor compounds - the organic mononitrites of 1,2-propanediol (PDNO) - were compared to GTN with regard to pulmonary selectivity and tolerance development. The vasodilatory effects of inorganic nitrite were investigated. MATERIALS AND METHODS: In anesthetized piglets, central hemodynamics were monitored. At normal pulmonary vascular resistance (PVR), IV infusions of PDNO (15-60 nmol kg-1 min-1), GTN (13-132 nmol kg-1 min-1), and inorganic nitrite (dosed as PDNO) were administered. At increased PVR (by U46619 IV), IV infusions of PDNO (60-240 nmol kg-1 min-1) and GTN (75-300 nmol kg-1 min-1) before and after a 5 h infusion of GTN (45 nmol kg-1 min-1) were given. RESULTS: At normal PVR, PDNO (n=12) and GTN (n=7) caused significant dose-dependent decreases in mean systemic and pulmonary arterial pressures, whereas inorganic nitrite (n=13) had no significant effect. At increased PVR, PDNO (n=6) and GTN (n=6) significantly decreased mean systemic and pulmonary pressures and resistances, but only PDNO reduced the ratio between pulmonary and systemic vascular resistances significantly. After the 5 h GTN infusion, the hemodynamic response to GTN infusions (n=6) was significantly suppressed, whereas PDNO (n=6) produced similar hemodynamic effects to those observed before the GTN infusion. CONCLUSION: PDNO is a vasodilator with selectivity for pulmonary circulation exhibiting no cross-tolerance to GTN, but GTN causes non selective vasodilatation with substantial tolerance development in the pulmonary and systemic circulations. Inorganic nitrite has no vasodilatory properties at relevant doses.

Beneficial effects of inhaled nitric oxide with intravenous steroid in an ischemia-reperfusion model involving aortic clamping.

This study evaluated the effects of inhaled nitric oxide (iNO) therapy combined with intravenous (IV) corticosteroids on hemodynamics, selected cytokines, and kidney messenger RNA toll-like receptor 4 (mRNA TLR4) expression in ischemia-reperfusion injury animal model. The primary endpoint was the evaluation of circulatory, respiratory, and renal function over time. We also investigated the profile of selected cytokines and high-mobility group box 1 (HMGB1) protein, as well as renal mRNA TLR4 activation determined by quantitative real-time polymerase chain reaction analysis. Pigs (n = 19) under sevoflurane AnaConDa anesthesia/sedation were randomized and subjected to abdominal laparotomy and alternatively suprarenal aortic cross-clamping (SRACC) for 90 min or sham surgery: Group 1 (n = 8) iNO (80 ppm) + IV corticosteroids (25 mg ×3) started 30 min before SRACC and continued 2 h after SRACC release, followed with decreased iNO (30 ppm) until the end of observation, Group 2 (n = 8) 90 min SRACC, Group 3 (n = 3)-sham surgery. Renal biopsies were sampled 1 hr before SRACC and at 3 and 20 h after SRACC release. Aortic clamping increased TLR4 mRNA expression in ischemic kidneys, but significant changes were recorded only in the control group ( P = 0.016). Treatment with iNO and hydrocortisone reduced TLR4 mRNA expression to pre-ischemic conditions, and the difference observed in mRNA expression was significant between control and treatment group after 3 h ( P = 0.042). Moreover, animals subjected to treatment with iNO and hydrocortisone displayed an attenuated systemic inflammatory response and lowered pulmonary vascular resistance plus increased oxygen delivery. The results indicated that iNO therapy combined with IV corticosteroids improved central and systemic hemodynamics, oxygen delivery, and diminished the systemic inflammatory response and renal mRNA TLR4 expression.

Comparison of anaesthetic gas consumption and stability of anaesthesia using automatic and manual control over the course of anaesthesia.

BACKGROUND: The automatic control module of end-tidal volatile agents (EtC) was designed to reduce the consumption of anaesthetic gases, increase the stability of general anaesthesia and reduce the need for adjustments in the settings of the anaesthesia machine. The aim of this study was to verify these hypotheses. METHODS: The course of general anaesthesia with the use of the EtC module was analysed for haemodynamic stability, depth of anaesthesia, end-expiratory concentration of anaesthetic, number of ventilator key presses, fentanyl supply, consumption of volatile agents and anaesthesia and operation times. These data were compared with the data obtained during general anaesthesia controlled manually and were processed with statistical tests. RESULTS: Seventy-four patients underwent general anaesthesia for scheduled operations. Group AUTO-ET (n = 35) was anaesthetized with EtC, and group MANUAL-ET (n = 39) was controlled manually. Both populations presented similar anaesthesia stability. No differences were noted in the time of anaesthesia, saturation up to MAC 1.0 or awakening. Data revealed no differences in mean EtAA or the fentanyl dose. The AUTO-ET group exhibited fewer key presses per minute, 0.0603 min⁻¹, whereas the MANUAL-ET exhibited a value of 0.0842 min⁻¹; P = 0.001. The automatic group consumed more anaesthetic and oxygen per minute (sevoflurane 0.1171 mL min⁻¹; IQR: 0.0503; oxygen 1.8286 mL min⁻¹, IQR: 1,3751) than MANUAL-ET (sevoflurane 0.0824 mL min⁻¹, IQR: 0.0305; oxygen 1,288 mL min⁻¹, IQR: 0,6517) (P = 0.0028 and P = 0.0171, respectively). CONCLUSION: Both methods are equally stable and safe for patients. The consumption of volatile agents was significantly increased in the AUTO-ET group. EtC considerably reduces the number of key presses.

Endotoxin Elimination in Patients with Septic Shock: An Observation Study.

To evaluate the effectiveness of endotoxin elimination with an adsorption column in patients with septic shock and endotoxemia. The elimination therapy was guided by a new bedside method of measuring endotoxin activity (EA). Intensive care unit (ICU) patients with septic shock and suspected Gram-negative infection were consecutively added to the study group within the first 24 h. Endotoxin elimination was performed using hemoperfusion with the Alteco LPS Adsorber. The primary endpoint was improvement in organ function within the first 24 h of treatment. A secondary objective was to assess the usefulness of a new method of measuring EA to help guide endotoxin elimination therapy. Out of 64 patients 18 had a high baseline EA [0.70 EA units (0.66-0.77)]. Those patients had endotoxin elimination treatment in addition to conventional medical therapy. At 24 h after endotoxin elimination, the EA had decreased to 0.56 EA units (0.43-0.77), (p = 0.005); MAP increased from 69 (62-80) to 80 mm Hg (68-88), (p = 0.002), and noradrenaline use decreased from 0.28 (0.15-0.80) to 0.1 µg/kg/min (0.00-0.70) at the same time (p = 0.04). The SOFA score had decreased from 11 (9-15) to 9 (7-14) points 24 h after endotoxin elimination (p = 0.01) with a median delta SOFA -2 points. Endotoxin elimination did not have a significant effect on the ICU length of stay or ICU mortality. Effective endotoxin elimination resulted in a significant improvement in hemodynamic parameters and of organ function. The application of the EA assay was useful for the bedside monitoring of endotoxemia in critically ill ICU patients.

Mechanical Ventilation in Children - Problems and Issues.

Respiratory failure is the leading reason for the admission of children to intensive care units, and the ventilator is the main therapeutic tool used during the treatment of these patients. A competently used ventilator and adequate knowledge of the anatomy, histology and physiology of the respiratory system in particular age groups of children (especially among neonates and infants) are crucial for successful treatment. Both non-invasive and invasive ventilation modes can be used for respiratory treatment in children. Invasive ventilation modes can be divided into two groups: conventional ones such as pressure-controlled or volume-controlled ventilation, or non-conventional modes such as oscillatory ventilation. Mechanical ventilation can involve a high risk of serious complications, such as pressure injury (barotrauma), volume injury (volutrauma) and biotrauma. Adhering to the principles of lung-protective ventilation can reduce the risk of side effects of mechanical ventilation.

Organ dysfunction among piglets treated with inhaled nitric oxide and intravenous hydrocortisone during prolonged endotoxin infusion.

OBJECTIVE: It has previously been shown that a combination of inhaled nitric oxide (iNO) and intravenous (IV) steroid attenuates endotoxin-induced organ damage in a 6-hour porcine endotoxemia model. We aimed to further explore these effects in a 30-hour model with attention to clinically important variables. DESIGN: Randomized controlled trial. SETTING: University animal laboratory. SUBJECTS: Domestic piglets (n = 30). INTERVENTIONS: Animals were randomized into 5 groups (n = 6 each): 1) Controls, 2) LPS-only (endotoxin/lipopolysaccharide (LPS) infusion), 3) LPS + iNO, 4) LPS + IV steroid, 5) LPS + iNO + IV steroid. MEASUREMENTS AND MAIN RESULTS: Exposure to LPS temporarily increased pulmonary artery mean pressure and impeded renal function with elevated serum creatinine and acidosis compared to a control group over the 30-hour study period. Double treatment with both iNO and IV steroid tended to blunt the deterioration in renal function, although the only significant effect was on Base Excess (p = 0.045). None of the LPS + iNO + IV steroid treated animals died during the study period, whereas one animal died in each of the other LPS-infused groups. CONCLUSIONS: This study suggests that combined early therapy with iNO and IV steroid is associated with partial protection of kidney function after 30 hours of experimental LPS infusion.

Advanced therapeutic methods for the treatment of meningococcal septic shock - case report.

BACKGROUND: Meningitis caused by Neisseria meningitidis is primarily a disease of children and young adults. If septic shock complicates the course of meningitis, it must be treated in the intensive care unit. CASE REPORT: An 18 year-old man with symptoms of meningococcal meningitis and clinical features of septic shock was admitted to the ICU. Tachycardia (heart rate 140 min⁻¹) required vasopressor to maintain blood pressure (noradrenalin 1 µg kg⁻¹ min⁻¹) on admission. Respiratory failure developed (respiratory rate of 40 min⁻¹, SaO2 79%, PaO2/FiO2 ratio = 55) and mechanical ventilatory support was used. The presence of Neisseria meningitidis was confirmed by a rapid latex agglutination test. Cefotaxime with vancomycin was administered on day one, and vancomycin was replaced by meropenem on day two. Additionally to the standard treatment of septic shock and multiorgan failure, haemoperfusion with LPS adsorber was performed to eliminate endotoxins from the bloodstream, and drotrecogin alfa was administered. Haemoperfusion was performed twice for sessions of two hours, and blood endotoxin activity decreased from 0.75 EAU to 0.4 EAU after 48 hours. The patient was admitted with signs of acute kidney injury and required continuous renal replacement therapy (Ca-Ca CVVHD, CVVHDF). CONCLUSIONS: Rapid pathogen identification, adequate antimicrobial therapy and endotoxin elimination from the bloodstream improved the haemodynamic and respiratory parameters of the patient. The application of routine plus non-standard methods of treatment of septic shock prevented the progression of the biological cascade in sepsis, and improved the patient's clinical condition.

[Severe acute respiratory distress syndrome complicating type A (H1N1) influenza treated with extracorporeal CO2 removal]. / Zespól ostrej niewydolnosci oddechowej w przebiegu grypy AH1N1 leczony skutecznie pozaustrojowa eliminacja CO2 .

BACKGROUND: The influenza pandemic of 2009 was reported to be frequently associated with pulmonary complications, including ARDS. We report the case of a morbidly obese, 37-year-old, AH1N1-infected woman, who was admitted to a regional hospital because of rapidly progressing respiratory failure. She was treated successfully with high frequency oscillatory ventilation (HFOV) and low-flow extracorporeal CO2 removal. CASE REPORT: The patient was admitted to a regional hospital because of severe viral infection, diabetes and hypertension that developed during pregnancy. On admission, she was deeply unconscious (GCS 5), hypotonic and anuric. Conventional ventilation, veno-venous haemofiltration, antibiotics and antiviral therapy (oseltamivir) did not improve the patient's condition, and she was transferred to a tertiary referral centre. Immediately before the transfer, she suffered two cardiac arrest episodes. They were successfully reversed. On admission, the patient was hypercapnic (PaCO2 150 mm Hg/20 kPa), acidotic (pH 6.92) and hyperkinetic (HR 120 min-1, CO 12.7 L min-1). Total lung compliance was 21 mL cm H2O-1, and SAP/DAP was 63/39 mm Hg). The PaO2/FIO2 index was 85. HFOV was instituted for 48 h, resulting in a marked improvement in gas exchange, however any manipulations caused immediate deterioration in the patient's condition. Extracorporeal CO2 removal was commenced and continued for 120 h, resulting in gradual improvement and eventual weaning from artificial ventilation after 17 days. Further treatment was complicated by septic shock due to Pseudomonas aeruginosa infection of the vagina, treated with piperacillin/tazobactam. The patient eventually recovered and returned to her regional hospital after 24 days. DISCUSSION: During the 2009 pandemic, a high number of pulmonary complications were observed all over the world. Viral infections are especially difficult to treat and the CESAR study indicated that the use of ECMO or extracorporeal CO2 removal devices may result in a lower mortality when compared with standard therapy. We conclude that the use of a simple CO2 removal device can be beneficial in complicated cases of AH1N1 influenza.

Prolonged exposure to inhaled nitric oxide does not affect haemostasis in piglets.

OBJECTIVE: To examine possible adverse effects on haemostasis from prolonged exposure to inhaled nitric oxide (iNO). DESIGN AND SETTING: Blinded, randomised, experimental animal study in a university animal laboratory. INTERVENTIONS: Anaesthetised and intubated piglets received central venous, arterial, and transabdominal urinary catheters. Twelve piglets were studied with triggered pressure support ventilation breathing with an air-oxygen mixture for 30 h with nitric oxide (NO), 40 parts per million (ppm) (n = 6) or without NO gas (n = 6) added. The tests of platelet function were assessed in a separate 1-h experiment in which 12 additional animals were blindly randomised to receive intravenous acetylsalicylic acid (ASA) (n = 7) or placebo (n = 5). MEASUREMENTS AND RESULTS: All 12 animals were clinically stable during the study period of 30 h. Haemostasis was assessed in terms of bleeding time and platelet function by Adeplat-S, reflecting platelet adhesion. Prothrombin fragment 1 + 2, fibrin D-dimer, tissue plasminogen activator and prothrombin complex were measured to investigate whether inhaled NO (iNO) had any effects on thrombin formation, fibrin formation, fibrinolysis or coagulation. All parameters including bleeding time and Adeplat-S were unaffected by iNO. ASA significantly increased bleeding time, but did not affect Adeplat-S. Nitrate in plasma and NOx (nitrate and nitrite) in urine increased significantly in pigs receiving iNO compared with controls. CONCLUSIONS: Prolonged exposure to iNO at 40[Symbol: see text]ppm did not affect bleeding time or coagulation parameters in healthy piglets. The findings do not support the hypothesis that iNO increases the risk of bleeding in humans.