Intubation Time, Lung Mechanics and Outcome in COVID-19 Patients Suffering Acute Respiratory Distress Syndrome: A Single-Center Study.

Background: We examined the effect of intubation time and the lung mechanics on clinical outcomes in coronavirus disease 2019 (COVID-19) patients. Methods: Based on the patient's hospital admission, intubation time was defined as early (≤ 2 days) or late (> 2 days). Patients were further divided into three groups; early (≤ 3 days), late (4 - 6 days), and very late (> 6 days) intubated. Results: A total of 194 patients were included; 66.5% male, median age 65 years. Fifty-eight patients (29.9%) were intubated early and 136 (70.1%) late. Early intubated patients revealed lower mortality (44.8% vs. 72%, P < 0.001), were younger (60 vs. 67, P = 0.002), had lower sequential organ failure assessment (SOFA) scores (6 vs. 8, P = 0.002) and higher lung compliance on admission days 1, 6 and 12 (42 vs. 36, P = 0.006; 40 vs. 33, P < 0.001; and 37.5 vs. 32, P < 0.001, respectively). Older age (adjusted odds ratio (aOR) = 1.15, P < 0.001), intubation time (aOR = 1.15, P = 0.004), high SOFA scores (aOR = 1.81, P < 0.001), low partial pressure of oxygen (PaO2)/fractional inspired oxygen tension (FiO2) ratio (aOR = 0.96, P = 0.001), and low lung compliance on admission days 1 and 12 (aOR = 1.12, P = 0.012 and aOR = 1.14, P < 0.001, respectively) were associated with higher mortality. Very late and late intubated patients had higher mortality rates than patients intubated early (78.4% vs. 63.4% vs. 44.6%, respectively, P < 0.001). Conclusions: Among COVID-19 intubated patients, age, late intubation, high SOFA scores, low PaO2/FiO2 ratio, and low lung compliance are associated with higher intensive care unit (ICU) mortality.

Impact of Bacterial Infections on COVID-19 Patients: Is Timing Important?

BACKGROUND: Along with important factors that worsen the clinical outcome of COVID-19, it has been described that bacterial infections among patients positive for a SARS-CoV-2 infection can play a dramatic role in the disease process. Co-infections or community-acquired infections are recognized within the first 48 h after the admission of patients. Superinfections occur at least 48 h after admission and are considered to contribute to a worse prognosis. Microbiologic parameters differentiate infections that happen after the fifth day of hospitalization from those appearing earlier. Specifically, after the fifth day, the detection of resistant bacteria increases and difficult microorganisms emerge. OBJECTIVES: The aim of the study was to evaluate the impact of bacterial infections in patients with COVID-19 on the length of the hospital stay and mortality. METHODS: A total of 177 patients hospitalized due to COVID-19 pneumonia were consecutively sampled during the third and fourth wave of the pandemic at a University Hospital in Greece. A confirmed bacterial infection was defined as positive blood, urinary, bronchoalveolar lavage (BAL) or any other infected body fluid. Patients with confirmed infections were further divided into subgroups according to the time from admission to the positive culture result. RESULTS: When comparing the groups of patients, those with a confirmed infection had increased odds of death (odds ratio: 3.634; CI 95%: 1.795-7.358; p < 0.001) and a longer length of hospital stay (median 13 vs. 7 days). A late onset of infection was the most common finding in our cohort and was an independent risk factor for in-hospital death. Mortality and the length of hospital stay significantly differed between the subgroups. CONCLUSION: In this case series, microbial infections were an independent risk factor for a worse outcome among patients with COVID-19. Further, a correlation between the onset of infection and a negative outcome in terms of non-infected, community-acquired, early hospital-acquired and late hospital-acquired infections was identified. Late hospital-acquired infections increased the mortality of COVID-19 patients whilst superinfections were responsible for an extended length of hospital stay.

Soluble Urokinase Plasminogen Activator Receptor as a Diagnostic and Prognostic Biomarker in Cardiac Disease.

This review summarizes the published literature referring to the use and validity of the biomarker soluble urokinase plasminogen activator receptor (suPAR) when used for the assessment of patients with cardiac diseases. It is measured by enzyme-linked immunosorbent assay (ELISA) in plasma samples. In cardiology a cut-off value range of 3.5 - 4.5 ng/mL has been commonly utilized. Different cut-off values may be applied based on the measuring kit used, the patient population and the clinical setting. A PubMed/Medline search was conducted aiming to identify all publications relevant to the use of suPAR in patients with cardiac diseases. A total of 39 studies were included in this review. suPAR as a marker of inflammation has been used more extensively in recent years, alone or in combination with other biomarkers of inflammation and cardiac pathology in the assessment of patients with acute and chronic cardiac diseases. suPAR is closely related to the pathophysiology of cardiac disease, and a number of publications encourages its use as a valuable biomarker in the assessment of patients presenting to the cardiology service. It may be most valuable in the risk assessment of patients with acute coronary syndromes and congestive heart failure, as suPAR elevation may be an independent predictor of mortality in these conditions. In conclusion, among several biomarkers used for clinical entities with underlying inflammatory pathophysiology including cardiac diseases, suPAR is a novel attractive index for the prognostic risk stratification of cardiac patients. More research is warranted to confirm its diagnostic and prognostic validity, alone or combined with other cardiac and inflammatory biomarkers.

The utility of brain natriuretic peptides in septic shock as markers for mortality and cardiac dysfunction: A systematic review.

OBJECTIVE: To conduct a systematic review evaluating the utility of brain natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) as biomarkers in adult patients with septic shock. MATERIALS AND METHODS: Pubmed/Medline databases were searched from inception to November 2018 using the search terms: (septic[Title/Abstract] AND shock[Title/Abstract]) AND bnp[Title/Abstract]) and (septic[Title/Abstract]) AND shock[Title/Abstract]) AND natriuretic[Title/Abstract]). No restriction was applied regarding date of publication. Comparative observational studies evaluating BNP and NT-proBNP in patients with septic shock aged ≥18 years were eligible for inclusion. Bibliographies from the extracted articles were also reviewed to identify additional relevant publications. RESULTS: In total, 46 studies met all eligibility criteria and were included. A strong body of literature has demonstrated that in patients with septic shock, increased values of BNP and NT-proBNP are associated with increased mortality. An increase from baseline BNP values has also been associated with increased mortality, whereas decreases from baseline values are not related to worse outcome. Brain natriuretic peptides have also been associated with cardiac dysfunction in patients with sepsis. Moreover, BNP values have been found to be significantly elevated in septic shock, regardless of cardiac dysfunction, and have been used to distinguish between septic and cardiogenic shock. Furthermore, BNP and NT-proBNP are significantly increased in patients with septic shock, compared to patients with sepsis and severe sepsis. CONCLUSIONS: BNP and NT-proBNP appear to be reliable predictors of outcome in septic shock.

Neutrophil-to-lymphocyte Ratio Relation to Sepsis Severity Scores and Inflammatory Biomarkers in Patients with Community-acquired Pneumonia: A Case Series.

BACKGROUND AND OBJECTIVES: Neutrophil to lymphocyte ratio (NLR) as calculated from the white cell differential blood count is considered a promising marker for the prognosis of patients with various diseases, including sepsis. This study was designed to assess the possible use of neutrophil-to-lymphocyte ratio in the prediction of survival outcomes in patients with community acquired pneumonia (CAP). A secondary objective was to compare the prognostic accuracy of NLR with the commonly used severity scores of sepsis SOFA, APACHE II and SAPS II. METHODS: This was a retrospective study based on data extracted from 26 patients suffering from acute CAP. The study period was from February 01, 2017 until April 30, 2017. All patients with CAP were presented in the Emergency Department (ED) of the University Hospital of Patras, Greece and were treated after admission in the Internal Medicine Department. The neutrophil-to-lymphocyte ratio (NLR) was calculated from the white blood cell count (WBC) values measured from a peripheral venous blood specimen drawn on admission. It was then compared with C-reactive protein (CRP) serum levels and the sepsis calculated prognostic scores APACHE II, SAPS II and SOFA. The impact of the above parameters was evaluated in relation to the final outcome. RESULTS: The mean period of hospitalization for the enrolled patients was 9.3 days (SD 5.8 days). Twenty-four patients (92.3%) got finally discharged from the hospital and two (7.7%) died during the hospitalization. Mean NLR and serum CRP values on admission were 10.2 ± 8.8 (min 1.4; max 34.7) and 11.4 ± 11 mg/dL (min 0.4; max 42.6) respectively. Based on the correlation analysis, serum CRP was more strongly positively correlated with NLR (r = 0.543, P = 0.004), than total WBC (r = 0.454, P = 0.02). None of the biomarkers of inflammation measured or computed in the study (CRP, WBC, NLR) showed any correlation with either the days of hospitalization or the sepsis prognostic scores. CONCLUSIONS: NLR shows a statistical significant correlation to the commonly used inflammatory markers CRP and total WBC in the small sample size of patients with CAP that we assessed. Although NLR is a simple, cheap and rapidly available measurement in the ED, future, larger prospective studies are warranted to confirm its possible value as a prognostic index in sepsis patients with CAP.

Inadvertent hypothermia and mortality in critically ill adults: Systematic review and meta-analysis.

OBJECTIVE: Considering that inadvertent hypothermia (IH) is common in Intensive Care Unit (ICU) patients and can be followed by severe complications, this systematic review identified, appraised and synthesised the published literature about the association between IH and mortality in adults admitted to the ICU. DATA SOURCES: By using key terms, literature searches were conducted in Pubmed, CINAHL, Cochrane Library, Web of Science and EMBASE. REVIEW METHODS: According to PRISMA guidelines, articles published between 1980-2016 in English-language, peer-reviewed journals were considered. IH was defined as core temperature of <36.5°C or lower, present on ICU admission or manifested during ICU stay. Outcome measure included ICU, hospital or 28-day mortality. Selected cohort studies were evaluated with the Newcastle-Ottawa Scale. Extracted data were summarised in tables and synthesised qualitatively and quantitatively, with adjusted odds ratios (ORs) for mortality being combined in meta-analyses. RESULTS: Eighteen observational studies met inclusion criteria. All of them had high methodological quality. In twelve out of fifteen studies, unadjusted mortality was significantly higher in hypothermic patients compared to non-hypothermic ones. Likewise, in thirteen out of sixteen studies, IH or lowest core temperature was independently associated with significantly higher mortality. High severity and long duration of IH were also associated with higher mortality. Mortality was significantly higher in patients with core temperature <36.0°C (pooled OR 2.093, 95% CI 1.704-2.570), and in those with core temperature <35.0°C (pooled OR 2.945, 95% CI 2.166-4.004). CONCLUSIONS: These findings indicate that IH predicts mortality in critically ill adults and pose suspicion that this may contribute to adverse patient outcome.

Electroencephalographic Abnormalities in Sepsis Patients in Correlation to the Calculated Prognostic Scores: A Case Series.

OBJECTIVE: To evaluate the electroencephalographic (EEG) findings and correlate EEG findings with inflammatory biomarkers and the sepsis prognostic scores SOFA, SAPS II and APACHE II in patients who present in the Emergency Department with sepsis without clinical central nervous system involvement. METHODS: The study included seventeen patients (< 70 years old) with sepsis without central nervous system involvement presenting in the Emergency Department of the University Hospital of Patras, Greece. All patients underwent neurologic examination and EEG analysis on admission to the hospital and were treated according to the international guideline protocols for sepsis. RESULTS: Six of seventeen sepsis patients had mild or moderate EEG abnormalities. We did not find any significant correlation between EEG abnormalities and inflammatory biomarkers (CRP, WBC) or commonly used prognostic sepsis scores. CONCLUSIONS: EEG could serve as a useful tool to identify brain alterations at an early stage in sepsis, before clinical sings of encephalopathy can be detected. However, the presence of EEG abnormalities does not correlate with sepsis severity as measured by the commonly used prognostic sepsis scores SOFA, APACHE II or SAPS II. Because this was a small single center observational study, large multi-center studies are warranted to confirm these findings.

C-Reactive Protein and Frailty in the Elderly: A Literature Review.

Chronic inflammation is a well-established background process in many age-related diseases. Many recent studies investigate the use of various inflammatory biomarkers such as C-reactive protein (CRP), interleukin-6, and interleukin-1 as predictors of physical and cognitive performance among elders. The phenotype of frailty has also been associated with underlying inflammatory mechanisms. The aim of this article was to review the literature referring to the correlation of CRP serum levels and frailty in older individuals. We tried to identify all relevant publications regarding the relation of CRP as an index of frailty in the elderly and its potential use. Although many studies in the recent medical literature positively associate serum CRP levels and frailty in older individuals, some do not, and some raise some interesting questions and set the basis for future studies. The association of CRP and frailty in elder patients should be considered when clinicians interpret inflammatory biomarkers in various clinical settings in such patients. Well-designed, prospective clinical trials are warranted to better assess the role and pathophysiology of frailty in the elderly and its mechanisms as also the exact role of CRP as an inflammatory marker and as a prognostic index in this syndrome.

The Use of Pulmonary Artery Catheter in Sepsis Patients: A Literature Review.

This article was to review the literature regarding the use of the pulmonary artery catheter (PAC) in the management of patients with sepsis and septic shock. A PubMed search was conducted in order to identify publications evaluating the use of PAC as a tool for management and therapeutic guidance in patients with sepsis. The bibliographies of all identified publications were reviewed for additional relevant references. Much information is identified in the literature regarding the indications for pulmonary artery catheterization in the assessment and treatment of patients with sepsis. Although the PAC has been widely used for many years, there is no clear benefit with regard to outcome, and there is controversy regarding its use. It is not clear that use of the PAC contributes to reduced morbidity and mortality in patients with sepsis. The role of the PAC is becoming less clear, as newer, non-invasive techniques are developed for hemodynamic assessment of sepsis patients. Large, well-designed clinical trials are needed to better assess the role and potential benefit from use of the PAC in sepsis.

Long QT Syndrome Leading to Multiple Cardiac Arrests After Posaconazole Administration in an Immune-Compromised Patient with Sepsis: An Unusual Case Report.

BACKGROUND: We present the case of a septic patient with severe immunodeficiency, who developed QT interval prolongation followed by episodes of lethal cardiac arrhythmia. Cardiac events occurred after posaconazole administration, incriminating posaconazole use, alone or in combination with voriconazole, as the culpable agent. CASE REPORT: A 26-year-old female patient underwent orthopedic surgery to remove ectopic calcifications in her left hip joint. On the first post-operative day she became septic due to a surgical wound infection. Despite being treated according to the therapeutic protocols for sepsis, no clinical improvement was noticed and further assessment revealed an underlying immunodeficiency. Considering the underlying immunodeficiency and to that point poor clinical response, an antifungal agent was added to the antibiotic regiment. Following discontinuation of multiple antifungal agents due to adverse effects, posaconazole was administered. Posaconazole oral intake was followed by episodes of bradycardia and QT interval prolongation. The patient suffered continuous incidents of cardiac arrest due to polymorphic ventricular tachycardia (torsades des pointes) that degenerated to lethal ventricular fibrillation. Posaconazole was immediately discontinued and a temporary pacemaker was installed. The patient finally recovered without any neurological deficit, and was discharged in a good clinical status. CONCLUSIONS: Close cardiac monitoring is recommended in cases where posaconazole administration is combined with coexisting risk factors, as they may lead to severe ECG abnormalities and cardiac arrhythmias such as long QT interval syndrome and torsades de pointes. Posaconazole interactions with medications metabolized via the CYP3A4 pathway should be considered an additional risk factor for lethal cardiac incidents.

The Use of Sodium Bicarbonate in the Treatment of Acidosis in Sepsis: A Literature Update on a Long Term Debate.

Introduction. Sepsis and its consequences such as metabolic acidosis are resulting in increased mortality. Although correction of metabolic acidosis with sodium bicarbonate seems a reasonable approach, there is ongoing debate regarding the role of bicarbonates as a therapeutic option. Methods. We conducted a PubMed literature search in order to identify published literature related to the effects of sodium bicarbonate treatment on metabolic acidosis due to sepsis. The search included all articles published in English in the last 35 years. Results. There is ongoing debate regarding the use of bicarbonates for the treatment of acidosis in sepsis, but there is a trend towards not using bicarbonate in sepsis patients with arterial blood gas pH > 7.15. Conclusions. Routine use of bicarbonate for treatment of severe acidemia and lactic acidosis due to sepsis is subject of controversy, and current opinion does not favor routine use of bicarbonates. However, available evidence is inconclusive, and more studies are required to determine the potential benefit, if any, of bicarbonate therapy in the sepsis patient with acidosis.

Pharmacokinetic changes and dosing modification of aminoglycosides in critically ill obese patients: a literature review.

The objective of the paper is to review the literature and provide recommendations for use of aminoglycoside antibiotics in critically ill obese patients. Literature search in PubMed for all articles on the use of aminoglycosides in critically ill obese patients was conducted, and all articles related to pharmacokinetics in obesity were reviewed. Bibliographies of all searched manuscripts were also reviewed in an attempt to find additional references. Although aminoglycoside pharmacokinetics have been described in detail, data on aminoglycoside use and appropriate dose modification in critically ill obese patients are very limited. Knowledge on aminoglycoside pharmacokinetics and use in critically ill obese patients is incomplete. Pathophysiologic changes in obesity can result in sub- or supra-therapeutic aminoglycoside plasma concentrations, especially in the presence of sepsis. Rigorous clinical studies are needed to establish aminoglycoside dosing guidelines in critically ill obese patients with sepsis.

Acute respiratory distress syndrome: pathophysiology and therapeutic options.

UNLABELLED: Acute Respiratory Distress Syndrome (ARDS) is a common entity in critical care. ARDS is associated with many diagnoses, including trauma and sepsis, can lead to multiple organ failure and has high mortality. The present article is a narrative review of the literature on ARDS, including ARDS pathophysiology and therapeutic options currently being evaluated or in use in clinical practice. The literature review covers relevant publications until January 2011. Recent developments in the therapeutic approach to ARDS include refinements of mechanical ventilatory support with emphasis on protective lung ventilation using low tidal volumes, increased PEEP with use of recruitment maneuvers to promote reopening of collapsed lung alveoli, prone position as rescue therapy for severe hypoxemia, and high frequency ventilation. Supportive measures in the management of ARDS include attention to fluid balance, restrictive transfusion strategies, and minimization of sedatives and neuromuscular blocking agents. Inhaled bronchodilators such as inhaled nitric oxide and prostaglandins confer short term improvement without proven effect on survival, but are currently used in many centers. Use of corticosteroids is also important, and appropriate timely use may reduce mortality. Finally, extra corporeal oxygenation methods are very useful as rescue therapy in patients with intractable hypoxemia, even though a survival benefit has not, to this date been demonstrated. Despite intense ongoing research on the pathophysiology and treatment of ARDS, mortality remains high. Many pharmacologic and supportive strategies have shown promising results, but data from large randomized clinical trials are needed to fully evaluate the true effectiveness of these therapies. KEYWORDS: ARDS; Pathophysiology; Treatment.