Setting and design
A before-and-after study design was employed. Two groups were defined. The first period included all consecutive patients with SCAP admitted between January 1995 and December 2000 (historical group). The second period included all consecutive patients with SCAP admitted between January 2005 and December 2010 (intervention group). The "4-year" hiatus corresponded to the progressive implementation of the new therapeutic strategies. The Ethics Committee of Tourcoing Hospital approved the study and waived the need for written informed consent in agreement with French regulations concerning retrospective studies (N°2011-01).
All patients ≥ 18 years of age who presented with CAP during the two studied periods were included. CAP was defined as the presence of a new pulmonary infiltrate on a chest radiograph at the initial presentation or that occurring within 48 hours following hospitalization along with the acute onset of two or more of the following signs or symptoms: fever, new or increasing cough or sputum production, dyspnea, pleuritic chest pain, new focal signs on chest examination, and leukocytosis or leukopenia as defined by local laboratory values. Patients were admitted to the ICU for mechanical ventilation (MV), for vasoactive drug support, or because the clinician believed that the individual was otherwise unstable and required intensive medical care. Patients were excluded for the following reasons: diagnosis of aspiration pneumonia, diagnosis of pneumocystis pneumonia, and if the Pneumonia Severity Index (PSI) score were ≤III . For patients with more than one admission for CAP in our unit, only the first admission was taken into account.
Collected baseline characteristics were age, gender, alcoholism, chronic obstructive pulmonary disease (COPD), congestive heart failure, cancer, immunosuppression, functional status, and diabetes mellitus. The diagnosis of COPD was based on the clinician’s assessment and included data provided by patients or relatives and found on previous medical reports. Congestive heart failure was defined as New York Heart Association (NYHA) class IV . Functional status was assessed by the Knaus score . Immunosuppression was defined as a recent use of immunosuppressants or systemic corticosteroids (i.e., prednisolone at >0.5 mg/kg/day for more than 1 month), human immunodeficiency virus infection, neutropenia (absolute neutrophil count of <1000 cells/mm3), organ transplantation with ongoing immunosuppressants, or cancer chemotherapy within the past 3 months. Patients with cancer were defined as those presenting with a diagnosis of a solid tumor or hematologic malignancy within 5 years of ICU admission.
Clinical and biological parameters collected upon ICU admission were the Simplified Acute Physiology Score (SAPS II) , Sequential Organ Failure Assessment (SOFA) score , PSI risk class, admission to the ICU within 24 hours after hospital admission, leukopenia (leukocyte count of <4000/mm3), PaO2:FIO2 in patients undergoing MV, an etiological diagnosis of pneumonia, and associated bacteremia. An etiologic diagnosis was considered when pathogens were isolated from (1) blood cultures, (2) pleural fluid, (3) sputum samples (bacterial growth in culture of endotracheal aspiration sample of ≥105cfu/mL in intubated patients), (4) a four-fold rise in IgG titers for Legionella pneumophila, Chlamydia pneumoniae, or Mycoplasma pneumoniae, (5) a single increased IgM titer for M. pneumoniae (≥1:16), Chl. pneumoniae (≥1:32), or Coxiella burnetii (≥1:64) or (6) positive urinary antigens for L. pneumophila type 1 or Streptococcus pneumoniae (tests performed during the second period of the study).
The recorded data on therapeutics performed within 48 hours after ICU admission were the class of delivered antimicrobial agents, antimicrobial combination therapy, adequacy of antimicrobial therapy, institution of antimicrobial therapy within 8 hours after hospital admission, NIMV and/or IMV, crystalloid or colloid fluid administration (first 24 hours after ICU admission), and requirement and nature of vasoactive agents. Antimicrobial therapy was considered to be adequate if the causative pathogens were susceptible to at least one of the delivered antimicrobial agents as shown on the antibiotic susceptibility reports. The recorded vasoactive drugs were dobutamine, dopamine, norepinephrine and epinephrine.
The recorded data on characteristics of the ICU stay were the mean tidal volume during the first 3 days of MV, transfusion requirement, occurrence of nosocomial infection, duration of MV, duration of ICU stay, and ICU mortality. Recorded nosocomial infections were ventilator-associated tracheobronchitis, ventilator-associated pneumonia, and bacteremia. Ventilator-associated tracheobronchitis, ventilator-associated pneumonia were defined according to previous reports [19, 20].
Standard process of care during the two studied periods
Vasoactive drugs: Pulmonary arterial catheterization was performed in patients with septic shock. The choice of vasopressor agents was left to each physician. Dobutamine was prescribed to increase oxygen delivery because it was the practice at that time .
Fluid therapy: Intravascular volume loading was assessed by physical examination and/or pulmonary arterial catheterization.
Insulin therapy: Insulin therapy was only prescribed for patients with diabetes mellitus who required insulin therapy at home.
MV: A tidal volume of 8 to 10 mL/kg was delivered after starting MV. The tidal volume was then modified according to the acid- base status, without specific limitations on the increase in the tidal volume.
Transfusion requirement: A hemoglobin level of ≥10 g/dL was required because of its widespread use in clinical medicine .
NIMV following extubation: NIMV was only used as rescue therapy when respiratory distress followed extubation.
Antimicrobial therapy: Our local hospital policy suggested treatment of SCAP with a beta-lactam plus fluoroquinolone according to the French recommendations published at the time . The beta-lactam was chosen by physicians among amoxicillin (50 mg/kg/d), amoxicillin/clavulanate (50 mg/kg/d), cefotaxime (50 mg/kg/d), or ceftriaxone (2 g/d). The fluoroquinolone was similarly chosen between ofloxacin (400 mg/d) or ciprofloxacin (800 mg/d).
New processes of care were progressively introduced in the unit during the period 2001_2004. An educational program based on the SSC guidelines was next implemented in our unit over a 1-month period (December 2004). The procedures were then written and made available to each physician in the unit.
Vasoactive drugs: The recommended vasopressor was norepinephrine. Dobutamine was only considered for patients with a low cardiac output in the presence of adequate left ventricular filling pressure and adequate mean arterial pressure as schown by echocardiography. The use of dobutamine for supranormal oxygen delivery was discontinued.
Fluid therapy: Intravascular volume loading was assessed by physical examination and/or arterial pulse pressure and/or echocardiography. Fluid responsiveness was determined by respiratory variations in the superior and inferior vena cava diameters, left ventricular stroke, and arterial pulse pressure .
Stress-dose steroid: Intravenous hydrocortisone was instituted in all septic patients who required vasopressor use.
Transfusion requirement: A restrictive red blood cell transfusion strategy was adopted targeting a hemoglobin level of 7 to 9 g/dL in all patients with the exception of those with acute myocardial infarcts or unstable angina, for whom a level of 10 g/dL level was required.
Low tidal volume: A tidal volume of 6 mL/kg was started in all patients undergoing MV. The tidal volume was then modified following blood gas analysis. Maintenance of an end-inspiratory plateau pressure of no more than 30 cm of H2O was a strict goal.
Insulin therapy: Insulin therapy was started in all patients to maintain a blood glucose level of <150 mg/dL.
NIMV: After a successful spontaneous breathing trial, NIMV was instituted within the next 24 hours following extubation procedures in patients with severe COPD (long-term oxygen therapy and noninvasive ventilation at home) and in patients with chronic cardiac failure (NYHA class IV).
Antimicrobial therapy: Between the two studied periods, our hospital guideline for empirical antimicrobial therapy in patients with CAP was modified according to international recommendations . A combination of a 3rdGC (cefotaxime or ceftriaxone) and a respiratory fluoroquinolone (levofloxacin) was suggested. Levofloxacin was discontinued after 3 days of delivery if Legionella urinary antigen tests remained negative.
Age, SAPS II, number of patients with MV or vasopressor support, and mortality for all CAP patients with CAP admitted to our unit during this period were reported.
The two studied groups were compared using the chi-squared test or Fisher's exact test for categorical parameters and Student’s t test for continuous variables. When appropriate, continuous variables were analyzed as categorical variables using clinically meaningful cut-off points.
The first objective of the study was to assess the mortality of patients during the two studied periods.
The second objective was to determine prognostic factors associated with outcome. We performed a univariate analysis including all patients to assess risk factors for mortality. Differences between the two studied groups were considered to be significant for variables yielding a p value of ≤0.05. To study the relationship between mortality and any predictor while taking the significant variables into account, we performed three stepwise logistic regressions as follows. The significant variables collected within 48 hours of admission were used for the first analysis, the therapeutic procedure instituted upon ICU admission and during the ICU stay were used for the second analysis, and all significant variables were entered into a third stepwise analysis. A level of p ≤0.15 was chosen for covariate retention.
The third objective of the study was to analyze the evolution of the SOFA score during the first week of ICU admission with a linear mixed model.
All statistical analyses were performed using the SAS Software, V9.1.