Christophe Guervilly

Long-term outcome in medical patients aged 80 or over following admission to an intensive care unit

IntroductionThe aim of this study was to evaluate factors influencing short- and long-term survival in medical patients aged 80 and over following admission to an intensive care unit.MethodsAll patients aged 80 years or over and admitted between 2001 and 2006 were included in this study. Survival was evaluated between the time of admission and June 2009; factors associated with mortality were determined. Health-related quality of life was evaluated using Short Form (SF)-36 in long-term survivors.ResultsFor the 299 patients included (mean age, 84 ± 4 y), hospital mortality was 55%. Factors independently associated with hospital mortality were a higher SAPS II score at ICU admission; the existence of a fatal disease as reflected by the McCabe score and a cardiac diagnosis at admission. In the 133 hospital survivors, median survival time was 710 days (95% CI, 499-921). Two-year mortality rates were 79% of the initial cohort and 53% of hospital survivors. The standardized ratio of mortality at 2 years after hospital discharge was 2.56 (95% CI, 2.08-3.12) when compared with age- and gender-adjusted mortality of the general population. Factors independently associated with mortality at 2 years after hospital discharge were SAPS II score at ICU admission and the McCabe score. Conversely, functional status prior to admission as assessed by Knaus or Karnofsky scores was not associated with long-term mortality. In long-term survivors, SF-36 physical function scores were poor but scores for pain, emotional well-being and social function were not much affected.ConclusionsThe severity of acute disease at admission influences mortality at the hospital and following discharge in patients aged 80 or over. Although up to 50% of patients discharged from the hospital were still alive at 2 years, mortality was increased when compared with the general population. Physical function of long-term hospital survivors was greatly altered.

Active cytomegalovirus infection is common in mechanically ventilated medical intensive care unit patients.

Objective:To assess the incidence, risk factors, and outcome of active cytomegalovirus (CMV) infection in nonimmunosuppressed intensive care unit (ICU) patients. Design:Prospective epidemiologic study. Setting:A medical ICU in a university hospital. Patients:Two hundred forty-two nonimmunosuppressed ICU patients mechanically ventilated for ≥2 days. Interventions:Routine pp65 antigenemia and serology for CMV were performed at admission, and then weekly. Bronchoalveolar lavage viral cultures were done when pneumonia was suspected. Measurements and Main Results:Thirty-nine of the 242 ICU patients (16.1%, confidence interval 11.5% to 20.7%) developed an active CMV infection, as diagnosed by positive antigenemia (85%) and/or positive rapid viral culture in bronchoalveolar lavage (26%). Antiviral treatment was initiated in 21 (54%) patients. ICU mortality (54% vs. 37%, p = 0.082) and in-hospital mortality (59% vs. 41%, p = 0.058) were increased in patients with active CMV infection, as compared with those without active CMV infection. Active CMV infection and Simplified Acute Physiology Score II at admission were associated with ICU death on multivariate analysis. The patients with active CMV infection had longer mechanical ventilation and longer ICU stay and were significantly more prone to developing bacterial nosocomial infections (p < 0.001). Logistic regression analysis showed that prior admission to other wards (p = 0.043; odds ratio [OR], 2.49), blood transfusions (p = 0.04; OR, 3.31), enteral feeding (p = 0.005; OR, 3.00), recent corticosteroid use before ICU admission (p = 0.08; OR, 2.26), and age (p = 0.07; OR, 1.026) were associated with the occurrence of active CMV infection. Conclusions:Active CMV infection is common among previously healthy patients under mechanical ventilation in a medical ICU. Further studies are needed to evaluate the role of antiviral treatments to reduce both the incidence and the outcome impact of active CMV infection.

Right ventricular function during high-frequency oscillatory ventilation in adults with acute respiratory distress syndrome.

Objective: To evaluate the effect of mean airway pressure under high-frequency oscillatory ventilation on right ventricular function. Design: Prospective randomized study. Setting: Intensive care unit of a tertiary care hospital. Patients: Sixteen consecutive patients within the first 48 hrs of mainly pulmonary acute respiratory distress syndrome. Interventions: After a 6-hr-period of protective conventional mechanical ventilation, patients were submitted to three 1-hr periods of high-frequency oscillatory ventilation (+ 5, + 10, + 15) in a randomized order, with a mean airway pressure level determined by adding 5, 10, or 15 cm H2O to the mean airway pressure recorded during conventional mechanical ventilation. Measurements and Main Results: Mean airway pressure was 18 ± 3 cm H2O during conventional mechanical ventilation and was increased until 33 ± 3 cm H2O at high-frequency oscillatory ventilation + 15. Right ventricular function was assessed using transesophageal echocardiography. During conventional mechanical ventilation, nine patients presented a right ventricular dysfunction (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.6) of whom four patients had a right ventricular failure (right ventricular end-diastolic area/left ventricular end-diastolic area ratio >0.9). High-frequency oscillatory ventilation + 10 and + 15 further worsened right ventricular function, resulting in about a 40% increase in right ventricular end-diastolic area/left ventricular end-diastolic area ratio and a 30% increase in end-diastolic eccentricity index when compared with conventional mechanical ventilation or high-frequency oscillatory ventilation + 5 periods. At high-frequency oscillatory ventilation + 15, 15 patients had right ventricular dysfunction and nine had right ventricular failure. High-frequency oscillatory ventilation did not improve oxygenation whatever the mean airway pressure level. A significant redistribution of tidal variation to the posterior parts of the lung was observed on electrical impedance tomography measurements when increasing mean airway pressure. However, this redistribution was not observed in patients who presented a worsening of right ventricular function (right ventricular end-diastolic area/left ventricular end-diastolic area increase >40%) at high-frequency oscillatory ventilation + 15. Conclusions: In patients with mainly pulmonary acute respiratory distress syndrome, using high mean airway pressure under high-frequency oscillatory ventilation can worsen right ventricular function when compared with protective conventional mechanical ventilation, notably in patients in whom high-frequency oscillatory ventilation produced less alveolar recruitment of the posterior parts of the lungs. This study highlights the interest of monitoring right ventricular function during high-frequency oscillatory ventilation. (Crit Care Med 2012; 40:–6)

High levels of circulating leukocyte microparticles are associated with better outcome in acute respiratory distress syndrome.

IntroductionThe current study has addressed the presence and the cellular origin of microparticles (MP) isolated from bronchoalveolar lavage (BAL) fluid and from blood samples from patients with acute respiratory distress syndrome (ARDS). Their prognostic interest was also investigated.MethodsFifty-two patients were included within the first 24 hours of ARDS. They were compared to spontaneous breathing (SB) and ventilated control (VC) groups. Bronchoalveolar lavage (BAL) and blood samples were obtained on Day 1 and Day 3 in an ARDS group. Leukocyte microparticles (LeuMP), neutrophil microparticles (NeuMP), endothelial microparticles (EMP), and platelet microparticles (PMP) were measured in arterial blood and in BAL samples by flow cytometry. Mortality from all causes was recorded at Day 28.ResultsAll MP subpopulations were detected in BAL. However, only LeuMP and NeuMP were elevated in ARDS patients compared to the SB group (P = 0.002 for both). Among ARDS patients, higher levels of LeuMP were detected in blood (Day 1) and in BAL (Day 3) in survivors as compared with the non survivors. Circulating LeuMP >60 elements/microliter detectable on Day 1 of ARDS, was associated with a higher survival rate (odds ratio, 5.26; 95% confidence interval, 1.10 to 24.99; P = 0.037).ConclusionsThe identification of the cellular origin of microparticles at the onset of ARDS has identified LeuMP as a biomarker of prognostic significance. The higher levels of LeuMP in survivors could be associated with a protective role of this MP subpopulation. This hypothesis needs further investigations.

Fluid management in acute lung injury and ards

ARDS is particularly characterized by pulmonary edema caused by an increase in pulmonary capillary permeability. It is considered that limiting pulmonary edema or accelerating its resorption through the modulation of fluid intake or oncotic pressure could be beneficial. This review discusses the principal clinical studies that have made it possible to progress in the optimization of the fluid state during ARDS. Notably, a randomized, multicenter study has suggested that fluid management with the goal to obtain zero fluid balance in ARDS patients without shock or renal failure significantly increases the number of days without mechanical ventilation. On the other hand, it is accepted that patients with hemodynamic failure must undergo early and adapted vascular filling. Liberal and conservative filling strategies are therefore complementary and should ideally follow each other in time in the same patient whose hemodynamic state progressively stabilizes. At present, although albumin treatment has been suggested to improve oxygenation transiently in ARDS patients, no sufficient evidence justifies its use to mitigate pulmonary edema and reduce respiratory morbidity. Finally, the resorption of alveolar edema occurs through an active mechanism, which can be pharmacologically upregluated. In this sense, the use of beta-2 agonists may be beneficial but further studies are needed to confirm preliminary promising results.

FIO2 and acute respiratory distress syndrome definition during lung protective ventilation.

Objective:Pao2/Fio2 ratio (P/F) is the marker of hypoxemia used in the American-European Consensus Conference on lung injury. A high Fio2 level has been reported to variably alter Pao2/Fio2. We investigated the effect of high Fio2 levels on the course of P/F in lung protective mechanically ventilated patients with acute respiratory distress syndrome. Design:Prospective, controlled, interventional study. Setting:University teaching French medical intensive care unit. Patients:Twenty-four patients with acute respiratory distress syndrome having P/F between 100 and 200 mm Hg at Fio2 0.5 received low-volume controlled ventilation (VT = 6 mL/kg predicted body weight) with a positive end-expiratory pressure at 2 cm H2O above the lower inflection point if present, or 10 cm H2O. Intervention:The following Fio2 levels were applied randomly for 20 mins: 0.5, 0.6, 0.7, 0.8, 0.9, and 1. Measurements and Results:Increasing Fio2 above 0.7 was associated with a significant increase in P/F (p < 0.001). The mean P/F change between Fio2 0.5 and 1 (Delta P/F) was 47% ± 35%. Sixteen patients (67%) had a P/F >200 at Fio2 1 whereas P/F was <200 at Fio2 0.5. Venous admixture (QVA/QT) decreased linearly for each Fio2 step (p < 0.001). The QVA/QT change between Fio2 0.5 and 1 was strongly correlated with Delta P/F (r = 0.84). Delta P/F was higher in patients with true shunt <30% (64% [54–93]) than in those with shunt >30% (20% [10–36]; p = 0.003). Conclusion:The P/F ratio increased significantly with a Fio2 >0.7. P/F variation, induced by a switch from Fio2 0.5 to 1, was responsible for two thirds of patients changing from the acute respiratory distress syndrome to the acute lung injury stage of the American-European Consensus Conference definition. Fio2 should be carefully defined for the screening of lung-injured patients.

Interferon-γ production by natural killer cells and cytomegalovirus in critically ill patients.

Objective:The mechanisms involved in cytomegalovirus reactivation in critically ill patients who were previously immunocompetent are still unknown. The current study was designed to evaluate the possible role of natural killer cells in the reactivation of cytomegalovirus in these patients. Design:Prospective observational. Setting:A medical intensive care unit of a university hospital. Patients:Fifty-one subjects, including 15 patients who experienced cytomegalovirus reactivation (cases) during their intensive care unit stay and 15 patients who matched intensive care unit controls, selected from a cohort of consecutive nonimmunocompromised intensive care unit patients, as well as healthy controls. Interventions:Tests included weekly systematic immunomonitoring and routine screening for cytomegalovirus infection until discharge from the intensive care unit or death. The immunophenotype and functions of natural killer cells were performed by flow cytometry, and serum levels of pro- and anti-inflammatory cytokines were determined by enzyme-linked immunosorbent assay. Measurements and Main Results:The overall occurrence of cytomegalovirus reactivation in the cohort was 27%. No differences of natural killer cell effector functions were observed at admission between cases and controls. Instead, before cytomegalovirus reactivation, the ability of natural killer cells to secrete interferon-&ggr; was significantly reduced in cases as compared with controls upon stimulation with antibody-coated target cells (p = .029) and with K562 cell stimulation (p = .029). No phenotypic or quantitative differences were observed between cases and controls. Cases exhibited higher levels of interleukin 10 (p = .031) and interleukin 15 (p = .021) than controls before cytomegalovirus reactivation. Conclusions:Impaired natural killer cell function with reduced interferon-&ggr; secretion precedes the occurrence of cytomegalovirus reactivation among previously immunocompetent critically ill patients.

Phenotype and Functions of Natural Killer Cells in Critically-Ill Septic Patients

Rationale Natural killer cells, as a major source of interferon-γ, contribute to the amplification of the inflammatory response as well as to mortality during severe sepsis in animal models. Objective We studied the phenotype and functions of circulating NK cells in critically-ill septic patients. Methods Blood samples were taken <48 hours after admission from 42 ICU patients with severe sepsis (n = 15) or septic shock (n = 14) (Sepsis group), non-septic SIRS (n = 13) (SIRS group), as well as 21 healthy controls. The immuno-phenotype and functions of NK cells were studied by flow cytometry. Results The absolute number of peripheral blood CD3–CD56+ NK cells was similarly reduced in all groups of ICU patients, but with a normal percentage of NK cells. When NK cell cytotoxicity was evaluated with degranulation assays (CD107 expression), no difference was observed between Sepsis patients and healthy controls. Under antibody-dependent cell cytotoxicity (ADCC) conditions, SIRS patients exhibited increased CD107 surface expression on NK cells (62.9[61.3–70]%) compared to healthy controls (43.5[32.1–53.1]%) or Sepsis patients (49.2[37.3–62.9]%) (p = 0.002). Compared to healthy (10.2[6.3–13.1]%), reduced interferon-γ production by NK cells (K562 stimulation) was observed in Sepsis group (6.2[2.2–9.9]%, p<0.01), and especially in patients with septic shock. Conversely, SIRS patients exhibited increased interferon-γ production (42.9[30.1–54.7]%) compared to Sepsis patients (18.4[11.7–35.7]%, p<0.01) or healthy controls (26.8[19.3–44.9]%, p = 0.09) in ADCC condition. Conclusions Extensive monitoring of the NK-cell phenotype and function in critically-ill septic patients revealed early decreased NK-cell function with impaired interferon-γ production. These results may aid future NK-based immuno-interventions. Trial Registration NTC00699868.

Comparison of femorofemoral and femorojugular configurations during venovenous extracorporeal membrane oxygenation for severe ARDS

Dear Editor, Schmidt et al. [1] recently demonstrated that an extracorporeal membrane oxygenation (ECMO) flow greater than 60 % of cardiac output was always associated with an SaO2 greater than 90 % during venovenous ECMO (vvECMO) for severe ARDS. We postulate that the configuration of the circuit may affect arterial oxygenation. We performed a retrospective comparative study of the medical charts of the patients according to ECMO configuration. During the oldest period, cannulation was performed with a femorofemoral (FF) configuration according to the experience of the ANZIC group [2], whereas during the latest period femorojugular (FJ) configuration was preferred. Details about the cannulas and the ECMO circuit’s components are available in previous publications [3, 4]. Nine patients with FF were compared with nine with FJ configuration (Table 1). In the case of the FF configuration, the drainage cannulation was inserted via the left femoral vein with the tip located at the junction between the iliac vein and the inferior vena cava, and the infusion cannula was inserted via the right femoral vein with the tip located at the junction between the right atrium and the inferior vena cava. In the case of the FJ configuration, the drainage cannula was inserted via the right femoral vein with the tip located at the junction

Does Admission During Morning Rounds Increase the Mortality of Patients in the Medical ICU

BACKGROUND Early optimization of treatment is crucial when admitting patients to the ICU and could depend on the organization of the medical team. The aim of this retrospective observational study was to determine whether admissions during morning rounds are independently associated with hospital mortality in a medical ICU. METHODS The 3,540 patients admitted from May 2000 to April 2010 to the medical ICU of Sainte Marguerite Hospital in Marseille, France, were divided into two groups based on the time of admission.The non-morning rounds group was admitted between 1:00 PM and 7:59 AM , and the morningrounds group was admitted between 8:00 AM and 12:59 PM . Hospital mortality (crude and adjusted)was compared between the two groups. RESULTS The 583 patients (16.5%) admitted during morning rounds were older and sicker upon admission compared with those patients admitted during non-morning rounds. The crude hospital mortality was 35.2% (95% CI , 31.4-39.1) in the group of patients admitted during morning rounds and 28.0% (95% CI, 26.4-29.7) in the other group ( P < .001). An admission during morning rounds was not independently associated with hospital death (adjusted hazard ratio, 1.10; 95% CI,0.94-1.28; P 5=.24). CONCLUSIONS Being admitted to the medical ICU during morning rounds is not associated with a poorer outcome than afternoon and night admissions. The conditions of the patients admitted during morning rounds were more severe, which underlines the importance of the ICU team’s availability during this time. Further studies are needed to evaluate if the presence of a specific medical team overnight in the wards would be able to improve patients’ outcome by preventing delayed ICU admission.