Characterisation and Outcomes of Patients with Solid Organ Malignancies Admitted to the Intensive Care Unit: Mortality and Impact on Functional Status and Oncological Treatment.

BACKGROUND: Despite the increasing number of ICU admissions among patients with solid tumours, there is a lack of tools with which to identify patients who may benefit from critical support. We aim to characterize the clinical profile and outcomes of patients with solid malignancies admitted to the ICU. METHODS: Retrospective observational study of patients with cancer non-electively admitted to the ICU of the Hospital Clinic of Barcelona (Spain) between January 2019 and December 2019. Data regarding patient and neoplasm characteristics, ICU admission features and outcomes were collected from medical records. RESULTS: 97 ICU admissions of 84 patients were analysed. Lung cancer (22.6%) was the most frequent neoplasm. Most of the patients had metastatic disease (79.5%) and were receiving oncological treatment (75%). The main reason for ICU admission was respiratory failure (38%). Intra-ICU and in-hospital mortality rates were 9.4% and 24%, respectively. Mortality rates at 1, 3 and 6 months were 19.6%, 36.1% and 53.6%. Liver metastasis, gastrointestinal cancer, hypoalbuminemia, elevated basal C-reactive protein, ECOG-PS greater than 2 at ICU admission, admission from ward and an APACHE II score over 14 were related to higher mortality. Functional status was severely affected at discharge, and oncological treatment was definitively discontinued in 40% of the patients. CONCLUSION: Medium-term mortality and functional deterioration of patients with solid cancers non-electively admitted to the ICU are high. Surrogate markers of cachexia, liver metastasis and poor ECOG-PS at ICU admission are risk factors for mortality.

Functional status and quality of life 12 months after discharge from a medical ICU in healthy elderly patients: a prospective observational study.

INTRODUCTION: Long-term outcomes of elderly patients after medical ICU care are little known. The aim of the study was to evaluate functional status and quality of life of elderly patients 12 months after discharge from a medical ICU. METHODS: We prospectively studied 112/230 healthy elderly patients (≥ 65 years surviving at least 12 months after ICU discharge) with full functional autonomy without cognitive impairment prior to ICU entry. The main diagnoses at admission using the Acute Physiology and Chronic Health Evaluation III (APACHE III) classification diagnosis and length of ICU stay and ICU scores (APACHE II, Sepsis-related Organ Failure Assessment (SOFA) and OMEGA) at admission and discharge were collected. Comprehensive geriatric assessment included the presence of the main geriatric syndromes and the application of Lawton, Barthel, and Charlson Indexes and Informant Questionnaire on Cognitive Decline to evaluate functionality, comorbidity and cognitive status, respectively. The EuroQol-5D assessed quality of life. Data were collected at baseline, during ICU and ward stay and 3, 6 and 12 months after hospital discharge. Paired or unpaired T-tests compared differences between groups (continuous variables), whereas the chi-square and Fisher exact tests were used for comparing dichotomous variables. For variables significant (P ≤ 0.1) on univariate analysis, a forward multiple regression analysis was performed. RESULTS: Only 48.9% of patients (mean age: 73.4 ± 5.5 years) were alive 12 months after discharge showing a significant decrease in functional autonomy (Lawton and Barthel Indexes) and quality of life (EuroQol-5D) compared to baseline status (P < 0.001, all). Multivariate analysis showed a higher Barthel Index and EQ-5D vas at hospital discharge to be associated factors of full functional recovery (P < 0.01, both). Thus, in patients with a Barthel Index ≥ 60 or EQ-5D vas ≥ 40 at discharge the hazard ratio for full functional recovery was 4.04 (95% CI: 1.58 to 10.33; P = 0.005) and 6.1 (95% CI: 1.9 to 19.9; P < 0.01), respectively. Geriatric syndromes increased after ICU stay and remained significantly increased during follow-up (P < 0.001). CONCLUSIONS: The survival rate of elderly medical patients 12 months after discharge from the ICU is low (49%), although functional status and quality of life remained similar to baseline in most of the survivors. However, there was a two-fold increase in the prevalence of geriatric syndromes.

Non-invasive ventilation after extubation in hypercapnic patients with chronic respiratory disorders: randomised controlled trial.

BACKGROUND: Non-invasive ventilation can prevent respiratory failure after extubation in individuals at increased risk of this complication, and enhanced survival in patients with hypercapnia has been recorded. We aimed to assess prospectively the effectiveness of non-invasive ventilation after extubation in patients with hypercapnia and as rescue therapy when respiratory failure develops. METHODS: We undertook a randomised controlled trial in three intensive-care units in Spain. We enrolled 106 mechanically ventilated patients with chronic respiratory disorders and hypercapnia after a successful spontaneous breathing trial. We randomly allocated participants by computer to receive after extubation either non-invasive ventilation for 24 h (n=54) or conventional oxygen treatment (n=52). The primary endpoint was avoidance of respiratory failure within 72 h after extubation. Analysis was by intention to treat. This trial is registered with clinicaltrials.gov, identifier NCT00539708. FINDINGS: Respiratory failure after extubation was less frequent in patients assigned non-invasive ventilation than in those allocated conventional oxygen therapy (8 [15%] vs 25 [48%]; odds ratio 5.32 [95% CI 2.11-13.46]; p<0.0001). In patients with respiratory failure, non-invasive ventilation as rescue therapy avoided reintubation in 17 of 27 patients. Non-invasive ventilation was independently associated with a lower risk of respiratory failure after extubation (adjusted odds ratio 0.17 [95% CI 0.06-0.44]; p<0.0001). 90-day mortality was lower in patients assigned non-invasive ventilation than in those allocated conventional oxygen (p=0.0146). INTERPRETATION: Early non-invasive ventilation after extubation diminished risk of respiratory failure and lowered 90-day mortality in patients with hypercapnia during a spontaneous breathing trial. Routine implementation of this strategy for management of mechanically ventilated patients with chronic respiratory disorders is advisable. FUNDING: IDIBAPS, CibeRes, Fondo de Investigaciones Sanitarias, European Respiratory Society.

Increased mortality in septic shock with the 4G/4G genotype of plasminogen activator inhibitor 1 in patients of white descent.

OBJECTIVE: To evaluate the effect of the 4G/5G PAI-1 gene polymorphism on the development of organ failure and outcome in critically ill patients with septic syndromes. DESIGN AND SETTING: Prospective, observational study in a medical intensive care unit of a university hospital. PATIENTS: 224 consecutively admitted patients. INTERVENTIONS: Epidemiological data, severity scores, and the primary site of infection were recorded. DNA genotyping of the PAI-1, TNF-beta, and IL1-ra genes, and measurement of plasma PAI-1 antigen and D-dimer were carried out. MEASUREMENTS: The primary outcome variables were organ dysfunction and mortality. RESULTS: Eighty-eight subjects had septic shock at ICU entry or within 48 h from admission. Homozygotes for the 4G allele exhibited higher plasma concentrations of PAI-1 antigen and D-dimer than 4G/5G and 5G/5G subjects). ICU mortality was 44.0% in patients with 4G/4G, 23.4% in 4G/5G and 12.5% in 5G/5G, mainly due to multiorgan failure. After adjusting for SAPS II at admission the genotypes independently associated with ICU mortality in septic shock were TNF-B2/B2 (OR 2.83, 1.04-7.67) and 4G/4G of PAI-1 (OR 2.23, 1.02-4.85). The PAI-1 genotype did not determine susceptibility to infection or the outcome in nonseptic systemic inflammatory response syndrome, sepsis, severe sepsis, and nosocomial septic shock. CONCLUSIONS: Homozygosity for 4G of the PAI-1 gene confers an increase in the risk of mortality in adult patients with septic shock due to a greater organ failure.

The effect of controlled drinking in alcoholic cardiomyopathy.

BACKGROUND: Cardiomyopathy is a potentially fatal complication of alcohol abuse. In alcoholic persons who develop cardiac dysfunction, abstinence is thought to be essential to halt further deterioration of cardiac contractility. Some evidence indicates that reducing alcohol intake may also be beneficial. OBJECTIVE: To evaluate the effect of moderate "controlled" drinking on cardiac function in patients with alcoholic cardiomyopathy. DESIGN: 4-year prospective cohort study. SETTING: A university hospital in Barcelona, Spain. PATIENTS: 55 alcoholic men with cardiomyopathy who had been drinking a minimum of 100 g of ethanol per day for at least 10 years. MEASUREMENTS: Evaluation of ethanol intake and nutrition, clinical assessment of cardiac status, and sequential echocardiography and radionuclide cardiac angiography. RESULTS: After the first year of evaluation, all patients with cardiomyopathy who abstained from alcoholic beverages demonstrated significant improvement in left ventricular function (average increase in left ventricular ejection fraction, 0.131 [95% CI, 0.069 to 0.193]). Patients who drank 20 to 60 g of ethanol per day showed a comparable mean improvement of 0.125 (CI, 0.082 to 0.168). In contrast, left ventricular ejection fraction deteriorated further in most patients who continued to abuse alcohol (>80 g/d). After 4 years, left ventricular ejection fraction had continued to improve in both abstinent patients and those who controlled their drinking. Ten patients who had continued to consume more than 80 g of ethanol per day died during the study. CONCLUSION: In patients with alcoholic cardiomyopathy, both abstinence and controlled drinking of up to 60 g of ethanol per day (four standard drinks) were comparably effective in promoting improvement in cardiac function.

Angiotensin-converting enzyme gene polymorphism is associated with vulnerability to alcoholic cardiomyopathy.

BACKGROUND: Chronic alcohol abuse has a dose-dependent toxic effect on the myocardium, leading to alcoholic cardiomyopathy. The fact that only a minority of persons with chronic alcoholism have this condition suggests the possibility of a genetic vulnerability. In this context, polymorphism of the angiotensin-converting enzyme (ACE) gene has been implicated in cardiac dysfunction. OBJECTIVE: To compare the ACE genotypes of alcoholic persons who have cardiomyopathy with those of comparable alcohol abusers who have normal cardiac function. DESIGN: Case-control study over a 2-year period. SETTING: An academic tertiary referral hospital in Barcelona, Spain. PATIENTS: 30 alcoholic men with symptomatic cardiomyopathy and 27 alcoholic men with normal cardiac function. MEASUREMENTS: Ethanol intake, cardiac status, left ventricular ejection fraction (LVEF), and ACE gene polymorphism. RESULTS: The DD ACE genotype was present in 57% of alcoholic persons with an LVEF less than 0.50 and in 7% of those with normal cardiac function. Compared with persons who had an I allele, the odds ratio for development of left ventricular dysfunction in alcoholic persons with the DD genotype was 16.4. CONCLUSIONS: Vulnerability to cardiomyopathy among chronic alcohol abusers is partially genetic and is related to presence of the ACE DD genotype. This finding demonstrates genetic susceptibility to alcohol-induced myocardial damage.

Pattern of soluble CD5 and CD6 lymphocyte receptors in critically ill patients with septic syndromes.

PURPOSE: Soluble forms of CD5 and CD6 lymphocyte surface receptors (sCD5 and sCD6) are molecules that seem to prevent experimental sepsis when exogenously administered. The aim of this study was to assess sCD5 and sCD6 levels in patients with septic syndromes. MATERIALS AND METHODS: The study population consisted of 218 patients admitted to the medical intensive care unit (ICU) presenting either septic syndromes or noninfectious systemic inflammatory response syndrome at admission or within the first 48 hours. The sCD5 and sCD6 levels were analyzed by sandwich enzyme-linked immunosorbent assay. RESULTS: Almost 50% of the patients had undetectable levels of sCD5 or sCD6, with no differences in clinical or biological variables with detectable patients. There was a correlation between the delta Sequential Organ Failure Assessment score and both sCD6 and sCD5 levels in all groups. Patients with sCD5 or sCD6 levels greater than 1500 ng/mL presented a higher in-ICU mortality (P < .05). Logistic regression analysis showed that increased sCD6 levels were associated with an increased risk of in-ICU mortality. CONCLUSIONS: Levels of sCD5 and sCD6 in critically ill patients with systemic inflammatory response syndrome present a high variation and an elevated proportion of undetectability. Levels of sCD6 are associated with an increased risk of mortality in these patients.

ADAMTS-13 in Critically Ill Patients With Septic Syndromes and Noninfectious Systemic Inflammatory Response Syndrome.

PURPOSE: Decreased ADAMTS-13 (A Disintegrin and Metalloprotease with a ThromboSpondin type 1 motif, member 13) seems to be associated with a poor prognosis in sepsis. However, its role in different septic syndromes and other causes of systemic inflammatory response syndrome (SIRS) remains unclear. The aims of this study were to assess ADAMTS-13 levels in patients with septic syndromes or noninfectious SIRS and to determine their association with morbidity and mortality. METHODS: The study population consisted of 178 patients admitted to the medical intensive care unit presenting either septic syndromes or noninfectious SIRS. ADAMTS-13 levels were analyzed. RESULTS: Patients with septic syndromes showed significantly lower levels of ADAMTS-13 compared with those with noninfectious SIRS (P = 0.014). Patients with severe sepsis or septic shock presented lower levels than those of patients with sepsis (P = 0.086). A significant negative correlation was found between ADAMTS-13 levels and delta Sequential Organ Failure Assessment and Acute Physiology and Chronic Health Evaluation II scores at admission in the septic patients. Patients who died had significantly lower levels of ADAMTS-13 compared with survivors, both in the whole population and among the septic patients (P = 0.002 and P = 0.009, respectively). Logistic regression analysis showed that decreased ADAMTS-13 levels were associated with an increased risk of in-intensive care unit mortality (odds ratio, 0.985; 95% confidence interval, 0.973-0.998; P = 0.023). CONCLUSIONS: Septic patients have lower levels of ADAMTS-13 than do patients with noninfectious SIRS. Levels of ADAMTS-13 are correlated with illness severity in patients with septic syndromes. ADAMTS-13 levels were associated with an increased risk of mortality in critically ill patients with SIRS especially those with septic syndromes.

Genotypes coding for low serum levels of mannose-binding lectin are underrepresented among individuals suffering from noninfectious systemic inflammatory response syndrome.

Gene polymorphisms, giving rise to low serum levels of mannose-binding lectin (MBL) or MBL-associated protease 2 (MASP2), have been associated with an increased risk of infections. The objective of this study was to assess the outcome of intensive care unit (ICU) patients with systemic inflammatory response syndrome (SIRS) regarding the existence of functionally relevant MBL2 and MASP2 gene polymorphisms. The study included 243 ICU patients with SIRS admitted to our hospital, as well as 104 healthy control subjects. MBL2 and MASP2 single nucleotide polymorphisms were genotyped using a sequence-based typing technique. No differences were observed regarding the frequencies of low-MBL genotypes (O/O and XA/O) and MASP2 polymorphisms between patients with SIRS and healthy controls. Interestingly, ICU patients with a noninfectious SIRS had a lower frequency for low-MBL genotypes and a higher frequency for high-MBL genotypes (A/A and A/XA) than either ICU patients with an infectious SIRS or healthy controls. The existence of low- or /high-MBL genotypes or a MASP2 polymorphism had no impact on the mortality rates of the included patients. The presence of high-MBL-producing genotypes in patients with a noninfectious insult is a risk factor for SIRS and ICU admission.

Mortality in healthy elderly patients after ICU admission.

PURPOSE: The aim of this study was to assess mortality in healthy elderly patients after non-elective medical ICU admission and to identify predictive factors of mortality in these patients. METHODS: Patients >or=65 years living at home and with full-autonomy (Barthel index, BI > 60), without cognitive impairment, and non-electively admitted to a medical ICU were prospectively recruited. A full comprehensive geriatric assessment was made with validated scales. RESULTS: A total of 230 patients were included, 110 (48%) between 65 and 74 years and 120 (52%) >or=75 years. No significant differences were observed between the two groups in premorbid functional and cognitive status, main diagnosis at ICU admission, APACHE II and SOFA scores, use of mechanical ventilation or haemodialysis or length of ICU stay. Over a mean follow-up of 522 days (range 20-1,170 days) the cumulative mortality of the whole group was 55%, being significantly higher in older subjects (62 vs. 47%; P = 0.024). On multivariate analysis, only parameters related to quality of life (QOL) and functional status were independent predictors of cumulated mortality (P < 0.01, both). Thus, in patients with EQ-5D(vas) (<70) or baseline Lawton index (LI) (<5) the hazard ratio for cumulated mortality was 2.45 (95% CI: 1.15-5.25; P = 0.03) and 4.10 (95% CI: 1.53-10.99; P = 0.006), respectively, compared to those with better scores. CONCLUSIONS: Healthy elderly non-elective medical patients admitted to the ICU have a high mortality rate related to premorbid QOL. The LI and/or EQ-5D(vas) may be useful tools to identify patients with the best chance of survival.

Yellow fever-associated viscerotropic disease in Barcelona, Spain.

Yellow fever vaccine is a live, attenuated viral preparation from the 17D virus strain. Since 1996, 34 cases of yellow fever vaccine-associated viscerotropic disease (YEL-AVD) have been described. We report a new case of YEL-AVD. Given the potential risks associated with the vaccine, physicians should consider vaccination only for patients truly at risk for exposure to yellow fever, especially for primovaccination.

Automatic control of tracheal tube cuff pressure in ventilated patients in semirecumbent position: a randomized trial.

OBJECTIVE: The aspiration of subglottic secretions colonized by bacteria pooled around the tracheal tube cuff due to inadvertent deflation (<20 cm H2O) of the cuff plays a relevant role in the pathogenesis of ventilator-associated pneumonia. We assessed the efficacy of an automatic, validated device for the continuous regulation of tracheal tube cuff pressure in preventing ventilator-associated pneumonia. DESIGN: Prospective randomized controlled trial. SETTING: Respiratory intensive care unit and general medical intensive care unit. PATIENTS: One hundred and forty-two mechanically ventilated patients (age, 64 +/- 17 yrs; Acute Physiology and Chronic Health Evaluation II score, 18 +/- 6) without pneumonia or aspiration at admission. INTERVENTIONS: Within 24 hrs of intubation, patients were randomly allocated to undergo continuous regulation of the cuff pressure with the automatic device (n = 73) or routine care of the cuff pressure (control group, n = 69). Patients remained in a semirecumbent position in bed. MEASUREMENTS AND MAIN RESULTS: The primary end point variable was the incidence of ventilator-associated pneumonia. Main causes for intubation were decreased consciousness (43, 30%) and exacerbation of chronic respiratory diseases (38, 27%). Cuff pressure <20 cm H2O was more frequently observed in the control than the automatic group (45.3 vs. 0.7% determinations, p < .001). However, the rate of ventilator-associated pneumonia with clinical criteria (16, 22% vs. 20, 29%) and microbiological confirmation (11, 15% vs. 10, 15%), the distribution of early and late onset, the causative microorganisms, and intensive care unit (20, 27% vs. 16, 23%) and hospital mortality (30, 41% vs. 23, 33%) were similar for the automatic and control groups, respectively. CONCLUSIONS: Cuff pressure is better controlled with the automatic device. However, it did not result in additional benefits to the semirecumbent position in preventing ventilator-associated pneumonia.

Up-regulation of myocardial L-type Ca2+ channel in chronic alcoholic subjects without cardiomyopathy.

BACKGROUND: Excessive ethanol intake is one of the most frequent causes of acquired dilated cardiomyopathy in developed countries. L-type Ca(2+) channels, involved in excitation-contraction coupling, are disturbed in animal models of persistent ethanol consumption. This study was designed to evaluate the density and function of myocardial L-type Ca(2+) channel receptors in organ donors with chronic alcoholism and controls. METHODS: The protein expression of L-type Ca(2+) channels was determined with (3)H-(+)-PN 200-110-binding experiments using a specific antibody against the alpha(1)-subunit in homogenate samples of left-ventricle apex from organ donors: healthy controls (n=11), chronic alcoholic without cardiomyopathy (n=12), and alcoholics with cardiomyopathy (n=11). Morphometric measurements of cardiomyocytes were performed. RESULTS: Binding experiments proved an up-regulation of L-type Ca(2+) channels expression in alcoholic patients compared with controls (B(max) 2.61 +/- 1.10 vs 1.33 +/- 0.49 fmol/mg, respectively; p<0.001). This up-regulation was present in the group of alcoholic subjects without cardiomyopathy, and was not seen in those with cardiomyopathy (3.39 +/- 2.20 vs 1.77 +/- 0.53 fmol/mg, respectively; p=0.02). The cross-sectional area and perimeter of the cells were greater in alcoholic patients with cardiomyopathy compared with controls and alcoholic patients without cardiomyopathy (500 +/- 87 vs 307 +/- 74 and 255 +/- 25 microm(2), respectively; p<0.001 both) as was the perimeter (78.7 +/- 7.7 vs 61.5 +/- 7.2 and 56.5 +/- 2.8 microm, respectively; p<0.001 both). Binding results did not change after adjusting receptor measurements for cross-sectional area and cell perimeter. CONCLUSIONS: Chronic alcoholism causes an up-regulation of myocardial L-type Ca(2+) channel receptors, which decreases when cardiomyopathy is present.