L Rabello

Critically ill patients with cancer and sepsis: Clinical course and prognostic factors ☆ ☆☆ ★

PURPOSE The purposes of this study were to evaluate the clinical course and to identify independent predictors of mortality in patients with cancer with sepsis. MATERIALS AND METHODS This is a secondary analysis of a prospective cohort study conducted at an oncological medical-surgical intensive care unit. Logistic regression was used to identify predictors of hospital mortality. RESULTS A total of 563 patients (77% solid tumor, 23% hematologic malignancies) were included over a 55-month period. The most frequent sites of infection were the lung, abdomen, and urinary tract; 91% patients had severe sepsis/septic shock. Gram-negative bacteria were responsible for more than half of the episodes of infection; 38% of patients had polymicrobial infections. Intensive care unit, hospital, and 6-month mortality rates were 51%, 65%, and 72%, respectively. In multivariate analyses, sepsis in the context of medical complications; active disease; compromised performance status; presence of 3 to 4 systemic inflammatory response syndrome criteria; and the presence of respiratory, renal, and cardiovascular failures were associated with increased mortality. Adjusting for other covariates, patients with non-urinary tract infections, mostly represented by patients with pneumonia and abdominal infections, had worse outcomes. CONCLUSIONS Sepsis remains a frequent complication in patients with cancer and associated with high mortality. Our results can be of help to assist intensivists in clinical decisions and to improve characterization and risk stratification in these patients.

Incidence and prognosis of ventilator-associated tracheobronchitis (TAVeM): a multicentre, prospective, observational study

BACKGROUND Ventilator-associated tracheobronchitis has been suggested as an intermediate process between tracheobronchial colonisation and ventilator-associated pneumonia in patients receiving mechanical ventilation. We aimed to establish the incidence and effect of ventilator-associated tracheobronchitis in a large, international patient cohort. METHODS We did a multicentre, prospective, observational study in 114 intensive care units (ICU) in Spain, France, Portugal, Brazil, Argentina, Ecuador, Bolivia, and Colombia over a preplanned time of 10 months. All patients older than 18 years admitted to an ICU who received invasive mechanical ventilation for more than 48 h were eligible. We prospectively obtained data for incidence of ventilator-associated lower respiratory tract infections, defined as ventilator-associated tracheobronchitis or ventilator-associated pneumonia. We grouped patients according to the presence or absence of such infections, and obtained data for the effect of appropriate antibiotics on progression of tracheobronchitis to pneumonia. Patients were followed up until death or discharge from hospital. To account for centre effects with a binary outcome, we fitted a generalised estimating equation model with a logit link, exchangeable correlation structure, and non-robust standard errors. This trial is registered with ClinicalTrials.gov, number NCT01791530. FINDINGS Between Sept 1, 2013, and July 31, 2014, we obtained data for 2960 eligible patients, of whom 689 (23%) developed ventilator-associated lower respiratory tract infections. The incidence of ventilator-associated tracheobronchitis and that of ventilator-associated pneumonia at baseline were similar (320 [11%; 10·2 of 1000 mechanically ventilated days] vs 369 [12%; 8·8 of 1000 mechanically ventilated days], p=0·48). Of the 320 patients with tracheobronchitis, 250 received appropriate antibiotic treatment and 70 received inappropriate antibiotics. 39 patients with tracheobronchitis progressed to pneumonia; however, the use of appropriate antibiotic therapy for tracheobronchitis was associated with significantly lower progression to pneumonia than was inappropriate treatment (19 [8%] of 250 vs 20 [29%] of 70, p<0·0001; crude odds ratio 0·21 [95% CI 0·11-0·41]). Significantly more patients with ventilator-associated pneumonia died (146 [40%] of 369) than those with tracheobronchitis (93 [29%] of 320) or absence of ventilator-associated lower respiratory tract infections (673 [30%] of 2271, p<0·0001). Median time to discharge from the ICU for survivors was significantly longer in the tracheobronchitis (21 days [IQR 15-34]) and pneumonia (22 [13-36]) groups than in the group with no ventilator-associated lower respiratory tract infections (12 [8-20]; hazard ratio 1·65 [95% CI 1·38-1·97], p<0·0001). INTERPRETATION This large database study emphasises that ventilator-associated tracheobronchitis is a major health problem worldwide, associated with high resources consumption in all countries. Our findings also show improved outcomes with use of appropriate antibiotic treatment for both ventilator-associated tracheobronchitis and ventilator-associated pneumonia, underlining the importance of treating both infections, since inappropriate treatment of tracheobronchitis was associated with a higher risk of progression to pneumonia. FUNDING None.

The impact of coagulation parameters on the outcomes of patients with severe community-acquired pneumonia requiring intensive care unit admission.

INTRODUCTION Coagulation abnormalities are frequent in patients with severe infections. However, the predictive value of d-dimer and of the presence of associated coagulation derangements in severe community-acquired pneumonia (CAP) remains to be thoroughly evaluated. The aim of this study was to investigate the predictive value of coagulation parameters in patients with severe CAP admitted to the intensive care unit. METHODS d-Dimer, antithrombin, International Society of Thrombosis and Hemostasis score, clinical variables, Sequential Organ Failure Assessment (SOFA), The Acute Physiology and Chronic Health Evaluation II (APACHE II) and the CURB-65 score were measured in the first 24 hours. Results are shown as median (25%-75% interquartile range). The main outcome measure was hospital mortality. RESULTS Ninety patients with severe CAP admitted to the intensive care unit were evaluated. Overall hospital mortality was 15.5%. d-Dimer levels in nonsurvivors were higher than those in survivors. In the univariate analysis, d-dimer, SOFA, and APACHE II scores were predictors of death. The discriminative ability of d-dimer (area under receiver operating curve = 0.75 [95% confidence interval, 0.64-0.83]; best cutoff for d-dimer was 1798 ng/mL) for in-hospital mortality was comparable with APACHE II and SOFA and better than C-reactive protein. Moreover, the addition of d-dimer to APACHE II or SOFA score increased the discriminative ability of both scores (area under the receiver operating curve = 0.82 [0.72-0.89] and 0.84 [0.75-0.91], respectively). CONCLUSIONS d-Dimer levels are good predictors of outcome in severe CAP and may augment the predictive ability of scoring systems as APACHE II and SOFA.

Antiphospholipid antibodies in critically ill patients with cancer: A prospective cohort study

PURPOSE The purpose of this study is to evaluate the prevalence and the prognostic impact of antiphospholipid antibodies (aPL) in critically ill cancer patients. METHODS This is a prospective cohort study in adult patients admitted to the intensive care unit for more than 48 hours at a cancer center. Clinical and laboratory data including coagulation parameters were obtained. Cox proportional hazard models were used to identify predictors of 6-month mortality. RESULTS Ninety-five (solid tumor, 79%; hematologic malignancies, 21%) patients were included, and aPL were identified in 74% of them. Median Simplified Acute Physiology Score 3 and Sequential Organ Failure Assessment scores were 51 (37-65) and 5 (2-8) points, respectively. The most frequent aPL were lupus anticoagulant (61%) and anti-β2 glicoprotein I (32%). Vascular complications occurred in 18% of patients and were comparable between aPL+ and aPL- patients. Sepsis and need for renal replacement therapy were more frequent in aPL+ patients. Hospital and 6-month mortality rates were 44% and 56%, respectively. Higher Sequential Organ Failure Assessment scores (each point) (hazard ratios [HR]=2.83 [95% confidence interval, 1.59-5.00]), medical admissions (HR=2.66 [1.34-5.27]), and d-dimer more than 500 ng/dL (HR=1.89 (1.04-3.44]) were independently associated with mortality. After adjusting for these covariates, aPL status was not associated with outcomes (HR=1.22 [0.60-2.47]). CONCLUSIONS Lupus anticoagulants were frequent in critically ill cancer patients. However, they were not associated with medium-term survival in these patients.

Clinical Outcomes and Microbiological Characteristics of Severe Pneumonia in Cancer Patients: A Prospective Cohort Study

Introduction Pneumonia is the most frequent type of infection in cancer patients and a frequent cause of ICU admission. The primary aims of this study were to describe the clinical and microbiological characteristics and outcomes in critically ill cancer patients with severe pneumonia. Methods Prospective cohort study in 325 adult cancer patients admitted to three ICUs with severe pneumonia not acquired in the hospital setting. Demographic, clinical and microbiological data were collected. Results There were 229 (71%) patients with solid tumors and 96 (29%) patients with hematological malignancies. 75% of all patients were in septic shock and 81% needed invasive mechanical ventilation. ICU and hospital mortality rates were 45.8% and 64.9%. Microbiological confirmation was present in 169 (52%) with a predominance of Gram negative bacteria [99 (58.6%)]. The most frequent pathogens were methicillin-sensitive S. aureus [42 (24.9%)], P. aeruginosa [41(24.3%)] and S. pneumonia [21 (12.4%)]. A relatively low incidence of MR [23 (13.6%)] was observed. Adequate antibiotics were prescribed for most patients [136 (80.5%)]. In multivariate analysis, septic shock at ICU admission [OR 5.52 (1.92–15.84)], the use of invasive MV [OR 12.74 (3.60–45.07)] and poor Performance Status [OR 3.00 (1.07–8.42)] were associated with increased hospital mortality. Conclusions Severe pneumonia is associated with high mortality rates in cancer patients. A relatively low rate of MR pathogens is observed and severity of illness and organ dysfunction seems to be the best predictors of outcome in this population.

Personalized treatment of severe pneumonia in cancer patients

Patients with cancer are at increased risk for sepsis as a consequence of immunosuppression. The hospital mortality remains elevated and it could be attributed to antibiotic failure because of the presence of multiresistant pathogens. Once the patient is critically ill, the use of the American Thoracic Society/Infectious Diseases Society of America classification does not seem very useful in the assessment of outcomes and the choice of antimicrobials. In critically ill patients, the characteristics of clinical response to antibiotics are usually inaccurate and occur late in the course of disease. So, the sequential evaluation of C-reactive protein-ratio is useful in the early identification of patients with antibiotic failure. To achieve safe and efficient antimicrobial therapy, we proposed an algorithm that may aid clinicians in their decision-making process.

C-reactive protein and procalcitonin profile in ventilator-associated lower respiratory infections

Purpose: Ventilator‐associated tracheobronchitis (VAT) has been suggested as an intermediate process between tracheobronchial colonization and ventilator‐associated pneumonia (VAP) in patients receiving mechanical ventilation. The aim of this study was to evaluate the ability of C‐reactive protein (CRP) and procalcitonin (PCT) to differentiate between VAT and VAP. Methods: Pre‐planned analysis of the prospective multinational TAVeM database, performed on 2960 patients receiving mechanical ventilation for >48 h, including 689 patients with VA‐LRTI. Patients with the diagnosis of VAT or VAP microbiologically documented and with one measurement of CRP and/or PCT on the day of diagnosis were included. Results: Four hundred and four patients (mean age 63 years, 298 men, ICU mortality 40%) were studied, 207 with VAT and 197 with VAP. On the day of infection diagnosis, the median CRP was elevated in both groups but significantly higher in VAP (18 mg/dL vs. 14 mg/dL, p = .001). Median PCT was also significantly higher in VAP (2.1 ng/dL vs. 0.64 ng/d L, p < .001). Both biomarkers could not help distinguish between VAT and VAP. Conclusion: Although PCT and CRP presented lower values in VAT as compared to VAP, there was a marked overlap of both biomarkers values in both VA‐LRTI not allowing adequate discrimination.

Patterns of C-reactive protein ratio response to antibiotics in pediatric sepsis: A prospective cohort study

Purpose: Evaluate sequential C‐reactive protein (CRP) measurements and patterns of CRP‐ratio response to antibiotic therapy during first 7 days in Pediatric Intensive Care Unit (PICU) of septic children. Methods: Prospective, cohort study of children (1 month‐12 years) admitted at 3 PICUs, with diagnosis of sepsis with <72 h course. CRP‐ratio was calculated in relation to D0_CRP value. Children were classified according to an individual pattern of CRP‐ratio response: fast – CRP_D4 of therapy was <0.4 of D0_CRP; slow – continuous but slow decrease of CRP; non – CRP remained ≥0.8 of D0_CRP; biphasic – initial CRP decrease to levels <0.8 of D0_CRP followed by secondary rise ≥0.8. Results: 103 septic children (age‐median: 2 yrs; 54% male) were prospectively included (infection focus: 65% respiratory, 12.5% central nervous system). Overall PICU mortality was 11.7%. 102 children could be classified according to a predefined CRP‐ratio response pattern. Time‐dependent analysis of CRP‐ratio and CRP course of the different patterns were significantly different. Besides, PICU mortality rate was significantly different according CRP‐ratio response patterns: fast response 4.5%; slow response 5.8%; non‐response 29.4%; biphasic response 42.8%. Conclusions: In pediatric sepsis, CRP‐ratio serial evaluation was useful in early identification of patients with poor outcome. HighlightsSequential evaluation of CRP and CRP‐ratio was useful in the early identification of pediatric septic critically ill patients with poor outcome.CRP‐ratio patterns of response to antibiotics during the first week of therapy are useful for the recognition of individual clinical evolution.Persistently elevated CRP‐ratio is associated with worse outcomes. A thorough evaluation to identify a cause for such evolution is granted.In time‐dependent analysis of PELOD score we found a significant decrease in survivors compared to non‐survivors.CRP is widely available, reliable and inexpensive inflammatory biomarker. This justifies its implementation in low‐resource settings.

Patterns of C-reactive protein ratio predicts outcomes in healthcare-associated pneumonia in critically ill patients with cancer

Purpose: Describe the patterns of C‐reactive protein relative changes in response to antibiotic therapy in critically ill cancer patients with healthcare‐associated pneumonia (HCAP) and its ability to predict outcome. Methods: Secondary analysis of a prospective cohort of critically ill cancer patients with HCAP. CRP was sampled every other day from D0 to D6 of antibiotic therapy. Patients were classified according to an individual pattern of CRP‐ratio response: fast – CRP at D4 of therapy was < 0.4 of D0 CRP; slow – a continuous but slow decrease of CRP; non – CRP remained ≥ 0.8 of D0 CRP; biphasic – initial CRP decrease to levels < 0.8 of the D0 CRP followed by a secondary rise ≥ 0.8. Results: 129 patients were included and septic shock was present in 74% and invasive mechanical ventilation was used in 73%. Intensive care unit (ICU) and hospital mortality rates were 47% and 64%, respectively. By D4, both CRP and CRP‐ratio of survivors were significantly lower than in nonsurvivors (p < 0.001 and p = 0.004, respectively). Both time‐dependent analysis of CRP‐ratio of the four previously defined patterns (p < 0.001) as ICU mortality were consistently different [fast 12.9%, slow 43.2%, biphasic 66.7% and non 71.8% (p < 0.001)]. Conclusion: CRP‐ratio was useful in the early prediction of poor outcomes in cancer patients with HCAP. HighlightsIn cancer patients with pneumonia, serial CRP‐ratio was useful in the early identification of patients with a poor outcome.The four patterns of the CRP‐ratio course during antibiotic therapy presented a clear correlation with ICU mortality.Fast response presented lower ICU mortality when compared with biphasic response and nonresponse (13% vs 67% vs 71.8%).An aggressive diagnostic and therapeutic approach should be attempted in patients with non/biphasic patterns of CRP‐ratio.To prevent further clinical deterioration, patients with non/biphasic patterns of CRP‐ratio should be cautiously evaluated.