Lower Respiratory Tract Infection and Short-Term Outcome in Patients With Acute Respiratory Distress Syndrome.

OBJECTIVE: To assess whether ventilator-associated lower respiratory tract infections (VA-LRTIs) are associated with mortality in critically ill patients with acute respiratory distress syndrome (ARDS). MATERIALS AND METHODS: Post hoc analysis of prospective cohort study including mechanically ventilated patients from a multicenter prospective observational study (TAVeM study); VA-LRTI was defined as either ventilator-associated tracheobronchitis (VAT) or ventilator-associated pneumonia (VAP) based on clinical criteria and microbiological confirmation. Association between intensive care unit (ICU) mortality in patients having ARDS with and without VA-LRTI was assessed through logistic regression controlling for relevant confounders. Association between VA-LRTI and duration of mechanical ventilation and ICU stay was assessed through competing risk analysis. Contribution of VA-LRTI to a mortality model over time was assessed through sequential random forest models. RESULTS: The cohort included 2960 patients of which 524 fulfilled criteria for ARDS; 21% had VA-LRTI (VAT = 10.3% and VAP = 10.7%). After controlling for illness severity and baseline health status, we could not find an association between VA-LRTI and ICU mortality (odds ratio: 1.07; 95% confidence interval: 0.62-1.83; P = .796); VA-LRTI was also not associated with prolonged ICU length of stay or duration of mechanical ventilation. The relative contribution of VA-LRTI to the random forest mortality model remained constant during time. The attributable VA-LRTI mortality for ARDS was higher than the attributable mortality for VA-LRTI alone. CONCLUSION: After controlling for relevant confounders, we could not find an association between occurrence of VA-LRTI and ICU mortality in patients with ARDS.

Improvement in process of care and outcome in patients requiring intensive care unit admission for community acquired pneumonia.

BACKGROUND: The present study was performed to assess the prognosis of patients admitted to the intensive care unit (ICU) for community acquired pneumonia (CAP) after implementation of new processes of care. METHODS: Two groups of patients with CAP were admitted to a 16-bed multidisciplinary ICU in an urban teaching hospital during two different periods: the years 1995-2000, corresponding to the historical group; and 2005-2010, corresponding to the intervention group. New therapeutic procedures were implemented during the period 2005-2010. These procedures included a sepsis management bundle derived from the Surviving Sepsis Campaign, use of a third-generation cephalosporin and levofloxacin as the initial empirical antimicrobial regimen, and noninvasive mechanical ventilation following extubation. RESULTS: A total of 317 patients were studied: 142 (44.8%) during the historical period and 175 (55.2%) during the intervention period. Sequential Organ Failure Assessment scores were higher in patients in the intervention group (7.2 ± 3.7 vs 6.2 ± 2.8; p=0.008). Mortality changed significantly between the two studied periods, decreasing from 43.6% in the historical group to 30.9% in the intervention group (p < 0.02). A restrictive transfusion strategy, use of systematic postextubation noninvasive mechanical ventilation in patients with severe chronic respiratory or cardiac failure patients, less frequent use of dobutamine and/or epinephrine in patients with sepsis or septic shock, and delivery of a third-generation cephalosporin associated with levofloxacin as empirical antimicrobial therapy were independently associated with better outcomes. CONCLUSION: Positive outcomes in ICU patients with CAP have significantly increased in our ICU in recent years. Many new interventions have contributed to this improvement.

Should highly active antiretroviral therapy be prescribed in critically ill HIV-infected patients during the ICU stay? A retrospective cohort study.

BACKGROUND: The impact of highly active antiretroviral therapy (HAART) in HIV-infected patients admitted to the intensive care unit (ICU) remains controversial. We evaluate impact of HAART prescription in HIV-infected patients admitted to the ICU of Tourcoing Hospital from January 2000 to December 2009. RESULTS: There were 91 admissions concerning 85 HIV-infected patients. Reasons for ICU admission were an AIDS-related diagnosis in 46 cases (51%). Fifty two patients (57%) were on HAART at the time of ICU admission, leading to 21 immunovirologic successes (23%). During the ICU stay, HAART was continued in 29 patients (32%), and started in 3 patients (3%). Only one patient experienced an adverse event related to HAART. Mortality rate in ICU and 6 months after ICU admission were respectively 19% and 27%. Kaplan-Meier estimates of the cumulative unajusted survival probability over 6 months were higher in patients treated with HAART during the ICU stay (Log rank: p = 0.04). No benefit of HAART in ICU was seen in the adjusted survival proportion at 6 months or during ICU stay. Prescription of HAART during ICU was associated with a trend to lower incidence of new AIDS-related events at 6 months (respectively 17% and 34% with and without HAART, p = 0.07), and with higher incidence of antiretroviral resistance after ICU stay (respectively 25% and 7% with and without HAART, p = 0.02). CONCLUSIONS: Our results suggest a lower death rate over 6 months in critically ill HIV-infected patients taking HAART during ICU stay. The optimal time to prescribe HAART in critically ill patients needs to be better defined.

Severe secondary peritonitis: impact of inappropriate initial antimicrobial therapy on prognosis and potential carbapenem-sparing.

BACKGROUND: Initiation of antimicrobial therapy (IAT) with broad-spectrum antibiotics is usual in Intensive Care Unit (ICU) patients with secondary peritonitis. Carbapenems are widely proposed by recent guidelines contrasting with current antibiotic stewardship policies of carbapenem-sparing. However, prognosis of inappropriate IAT remains unclear in these patients and broad-spectrum antibiotics are probably overused. We aimed to assess the role of inappropriate IAT in ICU patients with secondary peritonitis and the use of carbapenems in our IAT regimens. METHODS: We performed a retrospective analysis during a six-year period including 131 ICU patients with secondary peritonitis. We collected data concerning comorbidities, source and severity of peritonitis, management of IAT, peritoneal samples and outcome. RESULTS: Forty-one patients presented with community acquired peritonitis (CAP) and 90 with postoperative peritonitis (POP). Thirty-seven (28.2%) patients died during ICU stay. IAT was inappropriate in 35 (26.7%) patients. Inappropriate IAT was not associated with reduced survival with respectively 26 (27%) deaths when IAT was adequate and 11 (31.4%) deaths when IAT was inadequate (P=0.87). Inappropriate IAT was not associated with the need of re-operation and duration of ICU stay. Carbapenems were delivered in 29 patients but were only necessary for eight patients without alternative treatment. CONCLUSIONS: In our study, inappropriate IAT was not associated with a worse prognosis and carbapenems were overused. Extensive delivery of carbapenems proposed by recent guidelines could be reconsidered in the management of these patients.

Continuous Infusion of High Doses of Cefepime in Intensive Care Unit: Assessment of Steady-State Plasma Level and Incidence on Neurotoxicity.

Continuous infusion (CI) with high doses of cefepime is recommended in the empirical antimicrobial regimen of critically ill patients with suspected Gram-negative sepsis. This study aimed to determine factors associated with cefepime overdosing and the incidence of cefepime-induced neurotoxicity (CIN) in these patients. We performed a retrospective study including all patients receiving cefepime treatment between January 2019 and May 2022. The plasma level of cefepime defining overdosing was over 35 mg/L. Neurotoxicity was defined according to strict criteria and correlated with concomitant steady-state concentration of cefepime. Seventy-eight courses of cefepime treatment were analyzed. The mean cefepime plasma level at steady state was 59.8 ± 29.3 mg/L, and overdosing occurred in 80% of patients. Renal failure and a daily dose > 5 g were independently associated with overdosing. CIN was present in 30% of patients. In multivariate analysis, factors associated with CIN were chronic renal failure and a cefepime plasma concentration ≥ 60 mg/L. CIN was not associated with mortality. Overdosing is frequent in patients receiving high doses of cefepime by CI. Steady-state levels are higher than targeted therapeutic pharmacokinetic/pharmacodynamic objectives. The risk of CIN is important when the plasma concentration is ≥60 mg/L.

Severe pneumococcal pneumonia: impact of new quinolones on prognosis.

BACKGROUND: Most guidelines have been proposing, for more than 15 years, a ß-lactam combined with either a quinolone or a macrolide as empirical, first-line therapy of severe community acquired pneumonia (CAP) requiring ICU admission. Our goal was to evaluate the outcome of patients with severe CAP, focusing on the impact of new rather than old fluoroquinolones combined with ß-lactam in the empirical antimicrobial treatments. METHODS: Retrospective study of consecutive patients admitted in a 16-bed general intensive care unit (ICU), between January 1996 and January 2009, for severe (Pneumonia Severity Index > or = 4) community-acquired pneumonia due to non penicillin-resistant Streptococcus pneumoniae and treated with a ß-lactam combined with a fluoroquinolone. RESULTS: We included 70 patients of whom 38 received a ß-lactam combined with ofloxacin or ciprofloxacin and 32 combined with levofloxacin. Twenty six patients (37.1%) died in the ICU. Three independent factors associated with decreased survival in ICU were identified: septic shock on ICU admission (AOR = 10.6; 95% CI 2.87-39.3; p = 0.0004), age > 70 yrs. (AOR = 4.88; 95% CI 1.41-16.9; p = 0.01) and initial treatment with a ß-lactam combined with ofloxacin or ciprofloxacin (AOR = 4.1; 95% CI 1.13-15.13; p = 0.03). CONCLUSION: Our results suggest that, when combined to a ß-lactam, levofloxacin is associated with lower mortality than ofloxacin or ciprofloxacin in severe pneumococcal community-acquired pneumonia.

Resuscitation with low volume hydroxyethylstarch 130 kDa/0.4 is not associated with acute kidney injury.

INTRODUCTION: Acute kidney injury (AKI) in the ICU is associated with poorer prognosis. Hydroxyethylstarch (HES) solutions are fluid resuscitation colloids frequently used in the ICU with controversial nephrotoxic adverse effects. Our study objective was to evaluate HES impact on renal function and organ failures. METHODS: This observational retrospective study included 363 patients hospitalized for more than 72 hours in our ICU. A hundred and sixty eight patients received HES during their stay and 195 did not. We recorded patients' baseline characteristics on admission and type and volume of fluid resuscitation during the first 3 weeks of ICU stay. We also noted the evolution of urine output, the risk of renal dysfunction, injury to the kidney, failure of kidney function, loss of kidney function and end-stage kidney disease (RIFLE) classification and sepsis related organ failure assessment (SOFA) score over 3 weeks. RESULTS: Patients in the HES group were more severely ill on admission but AKI incidence was similar, as well as ICU mortality. The evolution of urine output (P = 0.74), RIFLE classification (P = 0.44) and SOFA score (P = 0.23) was not different. However, HES volumes administered were low (763+/-593 ml during the first 48 hours). CONCLUSIONS: Volume expansion with low volume HES 130 kDa/0.4 was not associated with AKI.

A pilot randomized study comparing high and low volume hemofiltration on vasopressor use in septic shock.

OBJECTIVE: High volume hemofiltration (HVHF) has shown potential benefits in septic animals and a few reports suggested a hemodynamic improvement in humans. However, randomized studies are still lacking. Our goal was to evaluate the hemodynamic effects of HVHF in septic shock patients with acute renal failure (ARF). DESIGN AND SETTING: Prospective randomized study in an intensive care unit (ICU). PATIENTS: Twenty patients with septic shock and ARF. INTERVENTIONS: Patients were randomized to either high volume hemofiltration [HVHF 65 ml/(kg h)] or low volume hemofiltration [LVHF 35 ml/(kg h). Vasopressor dose was adjusted to reach a mean arterial pressure (MAP) > 65 mmHg. MEASUREMENTS AND RESULTS: We performed six hourly measurements of MAP, norepinephrine dose, PaO(2)/FiO(2) and lactate, and four daily urine output and logistic organ dysfunction (LOD) score. Baseline characteristics of the two groups were comparable on randomization. Mean norepinephrine dose decreased more rapidly after 24 h of HVHF treatment compared to LVHF treatment (P = 0.004) whereas lactate and PaO(2)/FiO(2) did not differ between the two treatment groups. During the 4-day follow-up, urine output was slightly increased in the HVHF group (P = 0.059) but the LOD score evolution was not different. Duration of mechanical ventilation, renal replacement therapy and ICU length of stay were also comparable. Survival on day 28 was not affected. CONCLUSION: HVHF decreased vasopressor requirement and tended to increase urine output in septic shock patients with renal failure. However, a larger trial is required to confirm our results and perhaps to show a benefit in survival.

Lithium: one drug, five complications.

BACKGROUND: Lithium poisoning could trigger multiple complications. We report the case of a lithium poisoning with five complications that are described for the first time together. CASE REPORT: A 60-year-old woman was admitted in our intensive care unit for altered consciousness. Severe lithium intoxication was diagnosed (lithium plasmatic level 8.21 mmol/l) associated with acute oliguric kidney failure. Continuous renal replacement therapy was started immediately. Orotracheal intubation was quickly required because of status epilepticus. Medullary aplasia happened 48 h after the patient was intubated. Infectious and immunological causes were ruled out and lithium poisoning was considered as the most likely etiology. Iterative blood and platelet transfusion were required. Severe polyneuropathy was diagnosed on the 5th day after admission. The patient showed a peripheral tetraparesia and cranial nerve failure while lithium plasmatic level had decreased to a therapeutic level. Conversely, urine output increased and hypernatremia promptly occurred, which led to diabetes insipidus diagnosis. Neuropathy decreased in 72 h and the patient was definitely extubated by the 11th day. Hematologic disturbances decreased and no blood transfusion would be required after the 8th day. The patient would keep sequellas of the poisoning. Thin motricity would still be altered and polyuria would remain. Diffuse alopecia was promptly observed, with no iron deficiency or thyroid disturbance. CONCLUSION: In addition to presenting this case report, we herein discuss the drug causality, the consequences, and the plausible pathophysiology of these five situations.

Comparison of terminal extubation and terminal weaning as mechanical ventilation withdrawal in ICU patients.

BACKGROUND: Terminal extubation (TE) is applied in some Intensive Care Units (ICU) patients when a decision of withdrawal of mechanical ventilation is decided. Other units prefer terminal weaning (TW) with no removal of the endotracheal tube. We report our experience with these two procedures. METHODS: We conducted a retrospective study analyzing patients deceased in our ICU after a decision of life sustained therapy (LST) during the year 2013. TE was proposed to family members for patients presenting with two medical conditions: lack of vasoactive drugs (VAD) and SaO2>95% with a FIO2<50%. TW, defined by the reduction of oxygenation and/or the discontinuation of VAD, was proposed for patients receiving a FIO2≥50% and/or VAD. The two procedures were performed after obtaining a Cambridge Score-5 with sedatives. RESULTS: Sixty eight patients died after withdrawal of LST. TE was performed for 22 patients and TW for 46. There was no difference in mean age, mean length of ICU stay, cause of ICU admission and dose of sedatives used during withdrawal procedure between the two groups. All family members approved the decision of TE. In this group, family members of each patient were present in ICU room at time of death, while they were present at this moment for 32 (69.5%) patients with TW. CONCLUSIONS: In our Unit, TE is a practice largely approved by family members. This procedure does not require higher doses of sedatives and allows the nearest relatives to be present at time of death.

Impact of combination therapy and early de-escalation on outcome of ventilator-associated pneumonia caused by Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa is a common cause of ventilator-associated pneumonia (VAP). Guidelines recommend dual coverage of P. aeruginosa, but the beneficial effect of combination therapy is controversial. We described antibiotic prescriptions and evaluated the clinical impact of initial combination antibiotic therapy and de-escalation strategy in patients with VAP caused by P. aeruginosa. METHODS: Between 1994 and 2014, all 100 patients with VAP caused by P. aeruginosa in our intensive care unit (ICU) were included in a retrospective cohort study to evaluate the prognostic impact of initial combination antibiotic therapy. RESULTS: Eighty-five patients received initial combination antibiotic therapy and 15 monotherapy. Nine patients received inadequate initial antibiotic therapy. De-escalation was performed in 42 patients. Thirty-nine patients died in the ICU. Factors independently associated with death were SAPS II score [SAPS II ≥40 versus <40: hazard ratio (HR) 2.49, 95% confidence interval (CI) 1.08-5.70, p = 0.03] and septic shock (HR = 4.80, 95% CI = 1.90-12.16, p < 0.01) at onset of VAP. Initial combination antibiotic therapy (HR = 1.97, 95% CI = 0.56-6.93, p = 0.29) and early de-escalation (HR = 0.59, 95% CI = 0.27-1.31, p = 0.19) had no impact on mortality. In multivariate analysis, the risk for inappropriate initial antibiotic therapy was higher in cases with multi-drug resistant P. aeruginosa [odd ratio (OR) = 7.11, 95% CI = 1.42-35.51, p = 0.02], but lower in cases with initial combination antibiotic therapy (OR = 0.12, 95% CI = 0.02-0.63, p = 0.01). CONCLUSION: In our cohort, combination therapy increased the likelihood of appropriate therapy but did not seem to impact on mortality.

Procalcitonin kinetics in the prognosis of severe community-acquired pneumonia.

OBJECTIVES: Procalcitonin (PCT) kinetics is a good prognosis marker in infectious diseases, but few studies of community-acquired pneumonia (CAP) have been performed in intensive care units (ICU). We analyzed the relationship between PCT kinetics and outcome in ICU patients with severe CAP. DESIGN AND SETTING: Prospective observational study in a 16-bed university hospital ICU. PATIENTS: 100 critically ill patients with community-acquired pneumonia. MEASUREMENTS AND RESULTS: Median PCT was 5.2 ng/ml on day 1 and 2.9 ng/ml on day 3. It increased from day 1 to day 3 in nonsurvivors but decreased in survivors. In multivariate analysis four variables were associated with death: invasive ventilation (odds ratio 10-), multilobar involvement (5.6-), LOD score (6.9-), and PCT increase from day 1 to day 3 (4.5-). In intubated patients with a PCT level below 0.95 ng/ml on day 3 the survival rate was 95%. CONCLUSION: Increased PCT from day 1 to day 3 in severe CAP is a poor prognosis factor. A PCT level less than 0.95 ng/ml on day 3 in intubated patients is associated with a favorable outcome.

Survival in critically ill patients with acute kidney injury treated with early hemodiafiltration.

PURPOSE: Early renal replacement therapy (RRT) initiation should theoretically influence many physiological disorders related to acute kidney injury (AKI). Currently, there is no consensus about RRT timing in intensive care unit (ICU) patients. METHODS: We performed a retrospective analysis of all critically ill patients who received RRT in our ICU during a 3 year-period. Our goal was to identify mortality risk factors and if RRT initiation timing had an impact on survival. RRT timing was calculated from the moment the patient was classified as having acute kidney injury in the RIFLE classification. RESULTS: A hundred and ten patients received RRT. We identified four independent mortality risk factors: need for mechanical ventilation (OR = 12.82 (1.305 - 125.868, p = 0.0286); RRT initiation timing >16 h (OR = 5.66 (1.954 - 16.351), p = 0.0014); urine output on admission <500 ml/day (OR = 4.52 (1.666 - 12.251), p = 0.003); and SAPS II on admission >70 (OR = 3.45 (1.216 - 9.815), p = 0.02). The RRT initiation =16 h and RRT initiation >16 h groups presented the same baseline characteristics, except for more severe gravity scores and kidney failure in the early RRT group. CONCLUSIONS: Early RRT in ICU patients with acute kidney injury or failure was associated with increased survival.

Epidemiology, prognosis, and evolution of management of septic shock in a French intensive care unit: a five years survey.

Purpose. To evaluate the epidemiology, prognosis, and management of septic shock patients hospitalized in our intensive care unit (ICU). Materiel and Methods. Five-year monocenter observational study including 320 patients. Results. ICU mortality was 54.4%. Independent mortality risk factors were mechanical ventilation (OR = 4.97), Simplify Acute Physiology Score (SAPS) II > 60 (OR = 4.28), chronic alcoholism (OR = 3.38), age >65 years (OR = 2.65), prothrombin ratio <40% (OR = 2.37), and PaO(2)/FiO(2) ratio <150 (OR = 1.91). These six mortality risk factors recovered allow screening immediately septic shock patients with a high mortality risk. Morbidity improved with time (diminution of septic shock complications, increase of the number of days alive free from mechanical ventilation and vasopressors on day 28), concomitant to an evolution of the management (earlier institution of all replacement and medical therapies and more initial volume expansion). There was no difference in mortality. Conclusion. Our study confirms a high mortality rate in septic shock patients despite a new approach of treatment.

Validation of a prediction rule for prognosis of severe community-acquired pneumonia.

In a previous study, we developed a prognostic prediction rule, based on nine prognostic variables, capable to estimate and to adjust the mortality rate of patients admitted in intensive care unit for severe community-acquired pneumonia. A prospective multicenter study was undertaken to evaluate the performance of this rule. Five hundred eleven patients, over a 7-year period, were studied. The ICU mortality rate was 29.0%. In the 3 initial risk classes, we observed significantly increasing mortality rates (8.2% in class I, 22.8% in class II and 65.0% in class III) (p<0.001). Within each initial risk class, the adjustment risk score identified subclasses exhibiting significantly different mortality rates: 3.9% and 33.3% in class I; 3.1%, 12.9% and 63.3% in class II; and 55.8% and 82.5% in class III. Compared with mortality rates predicted by our previous study, only a few significant differences were observed. Our results demonstrate the performance and reproductibility of this prognostic prediction rule.

Impact of thrombocytopenia on outcome of patients admitted to ICU for severe community-acquired pneumonia.

OBJECTIVE: To evaluate the prevalence and the prognostic value of thrombocytopenia in patients admitted to ICU for severe community-acquired pneumonia. METHODS: Multicentre observational study was conducted in 7 ICUs in the north of France over a 19-year period (1987-2005). The primary outcome measure was the ICU mortality. RESULTS: Eight hundred and twenty-two patients were studied. A platelet count < 150x10(9)/L was observed at ICU admission in 202 (25%) patients. Admission platelet count was between 101 and 149x10(9)/L, 51 and 100x10(9)/L, 21 and 50x10(9)/L, and < or = 20x10(9)/L in 100, 61, 32 and 9 patients, respectively. ICU mortality rate was 35.4%. Classifying patients into 3 categories with the following cut-offs of platelet count, > or = 150x10(9)/L, 51-149x10(9)/L, and < or = 50x10(9)/L, we observed a significant increase in ICU mortality rates which were 30.8% in the first group, 44.1% in the second group and 70.7% in the last one (p<0.0001). In multivariate analysis, thrombocytopenia < or = 50x10(9)/L appeared as an independent predictor of mortality (AOR=4.386). CONCLUSIONS: In patients admitted to ICU for severe community-acquired pneumonia, thrombocytopenia has a high prevalence and influences the outcome.