Luís Coelho

Early identification of intensive care unit-acquired infections with daily monitoring of C-reactive protein: a prospective observational study.

IntroductionManifestations of sepsis are sensitive but are poorly specific of infection. Our aim was to assess the value of daily measurements of C-reactive protein (CRP), temperature and white cell count (WCC) in the early identification of intensive care unit (ICU)-acquired infections.MethodsWe undertook a prospective observational cohort study (14 month). All patients admitted for ≥72 hours (n = 181) were divided into an infected (n = 35) and a noninfected group (n = 28). Infected patients had a documented ICU-acquired infection and were not receiving antibiotics for at least 5 days before diagnosis. Noninfected patients never received antibiotics and were discharged alive. The progression of CRP, temperature and WCC from day -5 to day 0 (day of infection diagnosis or of ICU discharge) was analyzed. Patients were divided into four patterns of CRP course according to a cutoff value for infection diagnosis of 8.7 mg/dl: pattern A, day 0 CRP >8.7 mg/dl and, in the previous days, at least once below the cutoff; pattern B, CRP always >8.7 mg/dl; pattern C, day 0 CRP ≤8.7 mg/dl and, in the previous days, at least once above the cutoff; and pattern D, CRP always ≤8.7 mg/dl.ResultsCRP and the temperature time-course showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (P < 0.001 and P < 0.001, respectively). The area under the curve for the maximum daily CRP variation in infection prediction was 0.86 (95% confidence interval: 0.752–0.933). A maximum daily CRP variation >4.1 mg/dl was a good marker of infection prediction (sensitivity 92.1%, specificity 71.4%), and in combination with a CRP concentration >8.7 mg/dl the discriminative power increased even further (sensitivity 92.1%, specificity 82.1%). Infection was diagnosed in 92% and 90% of patients with patterns A and B, respectively, and in only two patients with patterns C and D (P < 0.001).ConclusionDaily CRP monitoring and the recognition of the CRP pattern could be useful in the prediction of ICU-acquired infections. Patients presenting maximum daily CRP variation >4.1 mg/dl plus a CRP level >8.7 mg/dl had an 88% risk of infection.

Usefulness of C-reactive protein in monitoring the severe community-acquired pneumonia clinical course

BackgroundThe aim of the present study was to evaluate the C-reactive protein level, the body temperature and the white cell count in patients after prescription of antibiotics in order to describe the clinical resolution of severe community-acquired pneumonia.MethodsA cohort of 53 consecutive patients with severe community-acquired pneumonia was studied. The C-reactive protein levels, body temperature and white cell count were monitored daily.ResultsBy day 3 a C-reactive protein level 0.5 times the initial level was a marker of poor outcome (sensitivity, 0.91; specificity, 0.59). Patients were divided according to their C-reactive protein patterns of response to antibiotics, into fast response, slow response, nonresponse, and biphasic response. About 96% of patients with a C-reactive protein pattern of fast response and 74% of patients with a slow response pattern survived, whereas those patients with the patterns of nonresponse and of biphasic response had a mortality rate of 100% and 33%, respectively (P < 0.001). On day 3 of antibiotic therapy, a decrease in C-reactive protein levels by 0.31 or more from the previous days level was a marker of good prognosis (sensitivity, 0.75; specificity, 0.85).ConclusionDaily C-reactive protein measurement after antibiotic prescription is useful in identification, as early as day 3, of severe community-acquired pneumonia patients with poor outcome. The identification of the C-reactive protein pattern of response to antibiotic therapy was useful in the recognition of the individual clinical course, either improving or worsening, as well as the rate of improvement, in patients with severe community-acquired pneumonia.

Patterns of c-reactive protein RATIO response in severe community-acquired pneumonia: a cohort study

IntroductionCommunity-acquired pneumonia (CAP) requiring intensive care unit (ICU) admission remains a severe medical condition, presenting ICU mortality rates reaching 30%. The aim of this study was to assess the value of different patterns of C-reactive protein (CRP)-ratio response to antibiotic therapy in patients with severe CAP requiring ICU admission as an early maker of outcome.MethodsIn total, 191 patients with severe CAP were prospectively included and CRP was sampled every other day from D1 to D7 of antibiotic prescription. CRP-ratio was calculated in relation to D1 CRP concentration. Patients were classified according to an individual pattern of CRP-ratio response with the following criteria: fast response - when D5 CRP was less than or equal to 0.4 of D1 CRP concentration; slow response - when D5 CRP was > 0.4 and D7 less than or equal to 0.8 of D1 CRP concentration; nonresponse - when D7 CRP was > 0.8 of D1 CRP concentration. Comparison between ICU survivors and non-survivors was performed.ResultsCRP-ratio from D1 to D7 decreased faster in survivors than in non-survivors (p = 0.01). The ability of CRP-ratio by D5 to predict ICU outcome assessed by the area under the ROC curve was 0.73 (95% Confidence Interval, 0.64 - 0.82). By D5, a CRP concentration above 0.5 of the initial level was a marker of poor outcome (sensitivity 0.81, specificity 0.58, positive likelihood ratio 1.93, negative likelihood ratio 0.33). The time-dependent analysis of CRP-ratio of the three patterns (fast response n = 66; slow response n = 81; nonresponse n = 44) was significantly different between groups (p < 0.001). The ICU mortality rate was considerably different according to the patterns of CRP-ratio response: fast response 4.8%, slow response 17.3% and nonresponse 36.4% (p < 0.001).ConclusionsIn severe CAP, sequential evaluation of CRP-ratio was useful in the early identification of patients with poor outcome. The evaluation of CRP-ratio pattern of response to antibiotics during the first week of therapy was useful in the recognition of the individual clinical evolution.

Pilot Study Evaluating C-Reactive Protein Levels in the Assessment of Response to Treatment of Severe Bloodstream Infection

We evaluated the usefulness of monitoring daily C-reactive protein (CRP) levels after initiation of antimicrobial therapy in 44 patients with bloodstream infection. The ratio of the CRP level during therapy to the level at the start of antimicrobial therapy (CRP ratio) was measured. A CRP ratio of >0.58 at day 4 of therapy was a marker of poor outcome (sensitivity, 0.89; specificity, 0.69). The recognition of a pattern of CRP-ratio response was useful in the prediction of individual clinical course.

Impact of systemic corticosteroids on the clinical course and outcomes of patients with severe community-acquired pneumonia: a cohort study.

INTRODUCTION Our aim was to evaluate the impact of corticosteroids on clinical course and outcomes of patients with severe community-acquired pneumonia (CAP) requiring invasive mechanical ventilation. METHODS This was a cohort study of patients with severe CAP from 2 intensive care units in tertiary hospitals in Brazil and Portugal. RESULTS A total of 111 patients were included (median age, 69 years; 56% men; 34% hospital mortality). Corticosteroids were prescribed in 61 (55%) patients. Main indications for their use were bronchospasm (52.5%) and septic shock (36%). Mortality rate of patients treated with and without corticosteroids was comparable (29.5% vs 32%, P = .837). No significant differences were observed on clinical course from day 1 to day 7 as assessed by the Sequential Organ Failure Assessment score (P = .95). Furthermore, C-reactive protein declined similarly in both groups (P = .147). In a multivariate analysis, mortality was associated with older age and higher Acute Physiology and Chronic Health Evaluation II score. CONCLUSIONS In patients with severe CAP requiring invasive mechanical ventilation, adjunctive therapy with corticosteroids did not influence intensive care unit and hospital mortality. In addition, no changes were observed on weaning from vasopressors, on recovery from organ failure/dysfunction as assessed by the Sequential Organ Failure Assessment score, as well as on C-reactive protein course.

Impact of fulminant hepatic failure in C-reactive protein?

INTRODUCTION Fulminant hepatic failure (FHF) refers to the rapid development of severe acute liver injury with impaired synthetic function, coagulopathy, and encephalopathy in a person who previously had a normal liver or had a well-compensated liver disease. It is a rare complication in critically ill patients and carries a very bad prognosis. Serum C-reactive protein (CRP), a useful marker of infection, is produced exclusively by the liver. AIM The aim of this study was to assess CRP concentrations in patients with FHF. METHODS We prospectively identified patients with sepsis and FHF treated at the intensive care unit (ICU). Data collected included admission diagnosis, medical history, systemic inflammatory response syndrome criteria, Acute Physiologic and Chronic Health Evaluation II, and Sequential Organ Failure Assessment scores. C-reactive protein and white cell count were measured at admission and then daily until ICU discharge. RESULTS We included 7 patients with FHF and sepsis. Six patients died with severe multiple organ failure. Six patients were already admitted with FHF, with the remaining one being diagnosed at the 26th day of ICU stay. All patients present severe coagulopathy. In all septic patients, despite clinical deterioration, CRP levels were markedly decreased sometimes reaching undetectable levels. CONCLUSION In septic patients with FHF, CRP is more a marker of severe liver dysfunction and should not be used as a marker of infection. As a result, in a patient admitted with a very high suspicion of infection and an abnormally low CRP concentration or with a marked CRP decline despite persistent septic shock, severe hepatic failure should be ruled out.

Metformin-induced lactic acidosis: a case series

IntroductionUnlike other agents used in the treatment of type 2 diabetes mellitus, metformin has been shown to reduce mortality in obese patients. It is therefore being increasingly used in higher doses. The major concern of many physicians is a possible risk of lactic acidosis. The reported frequency of metformin related lactic acidosis is 0.05 per 1000 patient-years; some authors advocate that this rate is equal in those patients not taking metformin.Case presentationWe present two case reports of metformin-associated lactic acidosis. The first case is a 77 year old female with a past medical history of hypertension and type 2 diabetes mellitus who had recently been prescribed metformin (3 g/day), perindopril and acetylsalicylic acid. She was admitted to the emergency department two weeks later with abdominal pain and psychomotor agitation. Physical examination revealed only signs of poor perfusion. Laboratory evaluation revealed hyperkalemia, elevated creatinine and blood urea nitrogen and mild leukocytosis. Arterial blood gases showed severe lactic acidemia. She was admitted to the intensive care unit. Vasopressor and ventilatory support was initiated and continuous venovenous hemodiafiltration was instituted. Twenty-four hours later, full clinical recovery was observed, with return to a normal serum lactate level. The patient was discharged from the intensive care unit on the sixth day. The second patient is a 69 year old male with a past medical history of hypertension, type 2 diabetes mellitus and ischemic heart disease who was on metformin (4 g/day), glycazide, acetylsalicylic acid and isosorbide dinitrate. He was admitted to the emergency department in shock with extreme bradycardia. Initial evaluation revealed severe lactic acidosis and elevated creatinine and urea. The patient was admitted to the Intensive Care Unit and commenced on continuous venovenous hemodiafiltration in addition to other supportive measures. A progressive recovery was observed and he was discharged from the intensive care unit on the seventh day.ConclusionWe present two case reports of severe lactic acidosis most probably associated with high doses of metformin in patients with no known contraindications for metformin prescription. In both patients no other condition was identified to cause such severe lactic acidosis. Although controversial, lactic acidosis should be considered in patients taking metformin.

Should C-reactive protein concentration at ICU discharge be used as a prognostic marker?

BackgroundAbout one third of hospital mortality in critically ill patients occurs after Intensive Care Unit (ICU) discharge. Some authors have recently hypothesized that unresolved or latent inflammation and sepsis may be an important factor that contributes to death following successful discharge from the ICU.AimThe aim of our study was to determine the ability of the clinical and inflammatory markers at ICU discharge to predict post-ICU mortality.MethodsA prospective observational cohort study was conducted during a 14-month period in an 8 bed polyvalent ICU. Acute Physiology and Chronic Health Evaluation (APACHE) II score, Simplified Acute Physiology Score (SAPS) II, Sequential Organ Failure Assessment (SOFA) score, Therapeutic Intervention Scoring System-28 (TISS-28), C-reactive protein (CRP), white cell count (WCC) and body temperature of the day of ICU discharge were collected from patients who survived their first ICU admission.ResultsDuring this period 156 patients were discharged alive from the ICU. A total of 29 patients (18.6%) died after ICU discharge. There were no differences in clinical and demographic characteristics between survivors and nonsurvivors. C-reactive protein levels at ICU discharge were not significantly different between survivors and nonsurvivors. The area under receiver operating characteristics curves of APACHE II, SAPS II, SOFA, TISS-28, CRP, WCC and body temperature at ICU discharge as prognostic markers of hospital death were 0.76 (95% confidence interval (CI) 0.67-0.86); 0.75 (95% CI 0.66-0.85); 0.72 (95% CI 0.62-0.83); 0.64 (95% CI 0.52-0.77); 0.55 (95% CI 0.43-0.67); 0.55 (95% CI 0.42-0.66) and 0.54 (95% CI 0.44-0.67) respectively. The hospital mortality rate of the patients with CRP <5, 5-10, >10 mg/dL was 15.1%, 16.1% and 33.3% respectively (p = NS).ConclusionsAt ICU discharge serum CRP concentration was a poor marker of post-ICU prognosis. Post-ICU death appears to be unrelated to the persistent inflammatory response.

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.

Intensive care unit patients with lower respiratory tract nosocomial infections: The ENIRRIs project

The clinical course of intensive care unit (ICU) patients may be complicated by a large spectrum of lower respiratory tract infections (LRTI), defined by specific epidemiological, clinical and microbiological aspects. A European network for ICU-related respiratory infections (ENIRRIs), supported by the European Respiratory Society, has been recently established, with the aim at studying all respiratory tract infective episodes except community-acquired ones. A multicentre, observational study is in progress, enrolling more than 1000 patients fulfilling the clinical, biochemical and radiological findings consistent with a LRTI. This article describes the methodology of this study. A specific interest is the clinical impact of non-ICU-acquired nosocomial pneumonia requiring ICU admission, non-ventilator-associated LRTIs occurring in the ICU, and ventilator-associated tracheobronchitis. The clinical meaning of microbiologically negative infectious episodes and specific details on antibiotic administration modalities, dosages and duration are also highlighted. Recently released guidelines address many unresolved questions which might be answered by such large-scale observational investigations. In light of the paucity of data regarding such topics, new interesting information is expected to be obtained from our network research activities, contributing to optimisation of care for critically ill patients in the ICU. Methodology for the first European network for ICU-related respiratory infections (ENIRRIs) project http://ow.ly/sud930fU1e7