Bench-to-bedside review: Nitric oxide in critical illness – update 2008

Nitric oxide (NO) is a unique and nearly ubiquitous molecule that is widely utilized as a signaling molecule in cells throughout the body. NO is highly diffusible, labile, and multiply reactive, suiting it well for its role as an important regulator of a number of diverse biologic processes, including vascular tone and permeability, platelet adhesion, neurotransmission, and mitochondrial respiration. NO can protect cells against antioxidant injury, can inhibit leukocyte adhesion, and can participate in antimicrobial defense, but can also have deleterious effects, including inhibition of enzyme function, promotion of DNA damage, and activation of inflammatory processes. This molecule's chemistry dictates its biologic activity, which can be both direct and indirect. In addition, NO has bimodal effects in a number of cells, maintaining homeostasis at low doses, and participating in pathophysiology in others. Perturbation of NO regulation is involved in the most important and prevalent disease processes in critical care units, including sepsis, acute lung injury, and multiple organ failure. Given that NO is ubiquitous, highly diffusible, and promiscuously reactive, its regulation is complex. The NO concentration, kinetics, and localization, both inside and outside the cell, are clearly crucial factors. In the present update we review a selection of studies that have yielded important information on these complex but important issues. Interpretation of these and other studies aimed at elucidating physiologic and pathophysiologic roles of NO must take this complexity into account. A full review of the role of NO in these diseases is beyond the scope of the current manuscript; the present article will focus on recent advances in understanding the complex role of NO in health and disease

Effect of ornithine on the ileal histology, nitric oxide production and lipid peroxidation in LPS-induced endotoxemia.

Effect of ornithine which is known to inhibit L-arginine uptake via cationic amino acid transport system has been tested, and compared to aminoguanidine, an iNOS inhibitor in lypopolysaccharide (LPS)-induced endotoxemia in rats. Serum nitrite/nitrate and malondialdehyde (MDA) level have been measured, and ileal histology has also been examined. Endotoxin increased serum nitrite/nitrate and MDA levels from 15.7+/- 2.4 micromol/ml and 2.1 +/-0.2 nmol/ml to 23.1 +/- 1.0 micromol/ml and 5.2+/- 0.3 nmol/ml (both P&#60;0.05), respectively. In addition, LPS caused ileal degeneration. L-ornithine (500 mg/kg) did not improve septic manifestations, i.e., serum nitrite/nitrate and MDA levels did not differ from those in endotoxemia. Neither does it have an improving action on ileal histology. However, higher dose of L-ornithine (2,500 mg/kg) lowered the increased level of nitrite/nitrate and MDA by LPS. Moreover, it restored ileal histology from grade 3 (median) to 0 (median) (P&#60;0.05). On the other hand, aminoguanidine (100 mg/kg) normalized serum nitrite/nitrate and MDA levels but not ileal histology in endotoxemic rats. In conclusion, high dose of L-ornithine could improve endotoxemic parameters in LPS-treated rats.</p

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

Contains fulltext : 172380.pdf (publisher's version ) (Open Access

A pilot study for treatment of severe COVID-19 pneumonia by aerosolized formulation of convalescent human immune plasma exosomes (ChipEXO™)

This is a single-center prospective, open-label, single arm interventional study to test the safety and efficacy of recently described ChipEXO™ for severe COVID-19 pneumonia. The ChipEXO™ is a natural product derived from convalescent human immune plasma of patients recovered from moderate COVID-19 infection. In September 2021, 13 patients with pending respiratory failure were treated with ChipEXO™ adapted for aerosolized formulation delivered via jet nebulizer. Patients received 1-5x1010 nano vesicle/5 mL in distilled water twice daily for five days as an add-on to ongoing conventional COVID-19 treatment. The primary endpoint was patient safety and survival over a 28-day follow-up. The secondary endpoint was longitudinal assessment of clinical parameters following ChipEXO™ to evaluate treatment response and gain insights into the pharmacodynamics. ChipEXO™ was tolerated well without any allergic reaction or acute toxicity. The survival rate was 84.6% and 11 out of 13 recovered without any sequel to lungs or other organs. ChipEXO™ treatment was effective immediately as shown in arterial blood gas analyses before and two hours after exosome inhalation. During the 5 days of treatment, there was a sustainable and gradual improvement on oxygenation parameters: i.e. respiratory rate (RR) [20.8% (P < 0.05)], oxygen saturation (SpO2) [6,7% (P < 0.05)] and partial pressure of oxygen to the fraction of inspired oxygen (PaO2/FiO2) [127.9% (P < 0.05)] that correlated with steep decrease in the disease activity scores and inflammatory markers, i.e. the sequential organ failure assessment (SOFA) score (75%, p < 0.05), C-reactive protein (46% p < 0.05), ferritin (58% p = 0.53), D-dimer (28% p=0.46). In conclusion, aerosolized ChipEXO™ showed promising safety and efficacy for life-threatening COVID-19 pneumonia. Further studies on larger patient populations are required to confirm our findings and understand the pathophysiology of improvement toward a new therapeutic agent for the treatment of severe COVID-19 pneumonia

Association of Energy Adequacy with 28-Day Mortality in Mechanically Ventilated Critically Ill

Objective: This study investigates the relationship of nutritional risk status with 28-day mortality in critically ill. Materials and Methods: This retrospective study included critically ill adult patients receiving >48 hours receiving mechanical ventilation. Data on baseline characteristics and the modified Nutritional Risk in Critically ill (mNUTRIC) score were collected on day 1. Energy intake was recorded daily until death, discharge or until twelfth evaluable days. Patients were divided into 2 groups: a) received = 75% of prescribed energy. Results: One hundred and fifty patients were included in the study. Patients with <75% of prescribed energy intake had longer length of ICU stay, duration of mechanical ventilation (p<0.001) and higher 28-day mortality (p<0.001). In the multi-logistic regression analysis, BMI (OR 0.87, CI 0.85-0.95, p<0.001) and mNUTRIC score (OR 2.3, CI 1.4-2.93, p<0.001) were associated with 28-day mortality. In subgroup analysis, the decrease in daily energy intake was associated with an increase in 28-day mortality in patients with a high mNUTRIC score (high mNUTRIC score OR 1.65, CI 1.20-1.70, p<0.001), but this relationship was not observed in the low mNUTRIC score group. Conclusion: The mNUTRIC score is associated with 28-day mortality in mechanically ventilated critically ill. In patients with a high mNUTRIC score, receiving 05% of the prescribed energy may positively affect patient outcomes

The initial resuscitation of septic shock

Septic shock is the most severe form of sepsis, characterized by (a) persistent hypotension despite fluid resuscitation and (b) the presence of tissue hypoperfusion. Delays in the diagnosis and initiation of treatment of septic shock is associated with increasing risk for mortality. Early and effective fluid resuscitation and vasopressor administration play a crucial role in maintaining tissue perfusion in septic shock patients. A low diastolic arterial pressure (DAP) correlates with severity of arteriolar vasodilation, compromises left ventricle oxygen supply and can be used for identifying septic shock patients thatwould potentially benefit fromearlier vasopressor therapy. Controversy currently exists as to the balance of fluids and vasopressors to maintain target mean arterial pressure. The aim of this article is to review the rationale for fluid resuscitation and vasopressor therapy and the importance of both mean and diastolic blood pressure during the initial resuscitation of the septic shock. We relate our personal prescription of balancing fluids and vasopressors in the resuscitation of septic shock. (c) 2020 Elsevier Inc. All rights reserved