Monitoring of circulating monocyte HLA-DR expression in a large cohort of intensive care patients: relation with secondary infections.

INTRODUCTION: The reports of an early and profound acquired immunodepression syndrome (AIDs) in ICU patients had gained sufficient credence to modify the paradigm of acute inflammation. However, despite several articles published on AIDs and its assessment by monocytic HLA-DR monitoring, several missing informations remained: 1-Which patients' are more prone to benefit from mHLA-DR measurement, 2-Is the nadir or the duration of the low mHLA-DR expression the main parameter to consider? 3-What are the compared performances of leukocytes' count analyses (lymphocyte, monocyte). MATERIAL AND METHOD: We conducted an observational study in a surgical ICU of a French tertiary hospital. A first mHLA-DR measurement (fixed flow cytometry protocol) was performed within the first 3 days following admission and a 2nd, between day 5 and 10. The other collected parameters were: SAPS II and SOFA scores, sex, age, comorbidities, mortality and ICU-acquired infections (IAI). The associations between mHLA-DR and outcomes were tested by adjusted Fine and Gray subdistribution competing risk models. RESULTS: 1053 patients were included in the study, of whom 592 had a 2nd mHLA-DR measurement. In this cohort, 223 patients (37.7%) complicated by IAI. The initial decrement in mHLA-DR was not associated with the later occurrence of IAI, (p = 0.721), however, the persistence of a low mHLA-DR (< 8000 AB/C), measured between day 5 and day 7, was associated with the later occurrence of IAI (p = 0.01). Similarly, a negative slope between the first and the second value was significantly associated with subsequent IAI (p = 0.009). The best performance of selected markers was obtained with the combination of the second mHLA-DR measurement with SAPSII on admission. Persisting lymphopenia and monocytopenia were not associated with later occurrence of IAI. CONCLUSION: Downregulation of mHLA-DR following admission is observed in a vast number of patients whatever the initial motif for admission. IAI mostly occurs among patients with a high severity score on admission suggesting that immune monitoring should be reserved to the most severe patients. The initial downregulation did not preclude the later development of IAI. A decreasing or a persisting low mHLA-DR expression below 8000AB/C within the first 7 days of ICU admission was independently and reliably associated with subsequent IAI among ICU patients with performances superior to leukocyte subsets count alone.

[Amniotic fluid embolism: an update]. / L'embolie amniotique : mise au point.

Amniotic fluid embolism (AFE) results from the passage of fœtal and amniotic fragments into the maternal circulation, occurring mostly within minutes before or after delivery. Although maternal and fœtal mortality of AFE remains high (about 40%), AFE should no longer be considered as having an ineluctable fatal course. Diagnosis is often made upon clinical presentation but histological confirmation is difficult owing favorable outcome and because an autopsy has not been performed. Identification of squamous cells in the maternal circulation could not confirm the diagnosis because of their possible maternal origin. High plasma level of insulin-like growth factor-binding protein-1 (IGFBP-1) has recently been identified as a biomarker of amniotic fluid passage into the maternal circulation and might therefore be used to confirm the diagnosis when lung tissue histology is not available. Treatment of AFE remains supportive with a special focus on correction of the coagulopathy and search for acute core pulmonale. In this later case, physicians should consider initiating an extracorporeal life support when facing a patient with refractory shock. Finally, caution is needed with the use of recombinant factor VIIa in this context.

Beyond single-marker analyses: mining whole genome scans for insights into treatment responses in severe sepsis.

Management of severe sepsis, an acute illness with high morbidity and mortality, suffers from the lack of effective biomarkers and largely empirical predictions of disease progression and therapeutic responses. We conducted a genome-wide association study using a large randomized clinical trial cohort to discover genetic biomarkers of response to therapy and prognosis utilizing novel approaches, including combination markers, to overcome limitations of single-marker analyses. Sepsis prognostic models were dominated by clinical variables with genetic markers less informative. In contrast, evidence for gene-gene interactions were identified for sepsis treatment responses with genetic biomarkers dominating models for predicting therapeutic responses, yielding candidates for replication in other cohorts.

[Out-of-hospital assessment of elderly patients' preference for ICU care]. / Évaluation préhospitalière du désir d'accès aux soins de réanimation chez les sujets âgés.

OBJECTIVE: To estimate the adequacy between elderly patients' preference for ICU care when treated for a life-threatening pathology, and the strategy proposed by the medical team on scene. STUDY DESIGN: Prospective, observational study. PATIENTS AND METHODS: All patients older than 80 treated out-of-hospital for a life threatening pathology were included, except in case of language barrier, or when patients were unable to answer and absence of next-of-kin. The results of the questionnaire on quality of life and patients' preference concerning ICU care were compared to the responses provided blindly by the medical team. RESULTS: Fifty-five patients were included. Quality of life as expressed by the patients was 7 (5-10) and by the physician 7 (6-8) (P=0.69). Thirty-six patients (65%) expressed the wish to be resuscitated, while ICU admission would have been proposed for 44 patients (80%) by the doctors (P=0.01). Among the 14 patients reluctant to ICU admission, 11 would have been proposed for ICU admission. In multivariate analysis, age (OR: 1.55 [1.04-2.32], P=0.03) and history of neurological pathology (OR: 11,91 [5.68->100], P=0.04) were associated with such an inadequacy. CONCLUSION: The inadequacy between elderly patients' preferences and doctors' opinion concerning ICU cares is frequent. The present results support a more systematic collection of patients' preferences when treated on scene for a life-threatening pathology.

[Transfers for postpartum haemorrhage in a Reference center (Lariboisière hospital): our experience during two years (2008 and 2009)]. / État des lieux des transferts pour hémorragie de la délivrance dans un centre de référence (hôpital Lariboisière) en 2008 et 2009.

OBJECTIVES: The postpartum haemorrhage (PPH) is the main cause of maternal mortality and is responsible in France every year of a quarter of the maternal deaths. We realized a study on the transfers for postpartum haemorrhage in 2008 and 2009 in a Reference center (Lariboisière Hospital). PATIENTS AND METHODS: It is a descriptive retrospective study over a period of two years, including all the patients cared for a postpartum haemorrhage. RESULTS: Two hundred and ninety-nine patients were cared for a PPH in 2008 and 2009 at the hospital Lariboisière. For transferred patients, the average age of the patients was of 30.9 years with varying extremes from 16 to 43 years old. It was the first pregnancy for 45.4% of the patients, having given birth to singletons (90.3%) by natural way in 63.8% of the cases. The care on arrival to Lariboisière based on surveillance in recovery room in 71.4% of the cases. The rate of embolisation was 22.4% and was stable over these two periods. DISCUSSION AND CONCLUSION: A supervision in recovery room associated with measures of resuscitation and with use of prostaglandins is mostly sufficient for the most part of the care of the PPH. In case of persistent bleeding, the embolisation remains an excellent therapeutic option and a good alternative in the hysterectomy of haemostasis, which however has to keep its place in severe PPH.

Time course of organ failure in patients with septic shock treated with hydrocortisone: results of the Corticus study.

INTRODUCTION: Corticosteroids have been proposed to decrease morbidity and mortality in patients with septic shock. An impact on morbidity should be anticipated to be earlier and more easily detected than the impact on mortality. METHODS: Prospective, randomized, double-blind, placebo-controlled study of 28-day mortality in patients with septic shock for <72 h who underwent a short high-dose ACTH test in 52 centers in 9 European countries. Patients received 11-day treatment with hydrocortisone or placebo. Organ dysfunction/failure was quantified by the use of the sequential organ failure assessment (SOFA) score. RESULTS: From March 2002 to November 2005, 499 patients were enrolled (hydrocortisone 251, placebo 248). Both groups presented a similar SOFA score at baseline (hydrocortisone 10.8 ± 3.2 vs. placebo 10.7 ± 3.1 points). There was no difference in 28-day mortality between the two treatment groups (hydrocortisone 34.3% vs. placebo 31.5%). There was a decrease in the SOFA score of hydrocortisone-treated patients from day 0 to day 7 compared to the placebo-treated patients (p = 0.0027), driven by an improvement in cardiovascular organ dysfunction/failure (p = 0.0005) and in liver failure (p < 0.0001) in the hydrocortisone-treated patients. CONCLUSION: Patients randomized to treatment with hydrocortisone demonstrated a faster decrease in total organ dysfunction/failure determined by the SOFA score, primarily driven by a faster improvement in cardiovascular organ dysfunction/failure. This organ dysfunction/failure improvement was not accompanied by a decreased mortality.

Serum oxytocin concentrations in elective caesarean delivery: a randomized comparison of three infusion regimens.

BACKGROUND: The aim of this study was to determine serum oxytocin concentrations following different regimens of prophylactic oxytocin administration in women undergoing elective caesarean delivery. METHODS: Thirty healthy pregnant patients were randomized, after clamping of the umbilical cord, to receive intravenous oxytocin in one of the following groups: G1 (n=9), 10 IU of oxytocin infused over 30 min (0.33 IU/min); G2 (n=11), 10 IU of oxytocin infused over 3 min and 45 s (2.67 IU/min); and G3 (n=10), 80 IU of oxytocin infused over 30 min (2.67 IU/min). Both patient and surgeon were blinded to allocation. Uterine tone was assessed by surgical palpation. Serum oxytocin concentration was determined by enzyme immunoassay before anaesthesia (T0) and at 5 (T5), 30 (T30) and 60 (T60) min after the start of oxytocin infusion. RESULTS: Serum oxytocin concentrations (mean±standard error, ng/mL) were not significantly different in the groups at T0 (0.06±0.02, 0.04±0.02 and 0.07±0.04, respectively, P=0.76), and T60 (0.65±0.26, 0.36±0.26 and 0.69±0.26, respectively, P=0.58). G3 showed higher concentrations than G1 at T5 (3.65±0.74 versus 0.71±0.27, P=0.01) and at T30 (6.19±1.19 versus 1.17±0.37, P<0.01), and were higher than G2 at T30 (6.19±1.19 versus 0.41±0.2, P<0.01). Haemodynamic data and uterine tone were considered satisfactory and similar in all groups. No additional uterotonic agents were needed. CONCLUSION: Serum oxytocin measurements made using enzyme immunoassay in healthy pregnant women undergoing elective caesarean delivery showed that administration of 80 IU oxytocin over 30 min resulted in higher serum oxytocin levels after 5 and 30 min than the two other regimens. The concentrations did not differ between groups at 60 min.

Is monocyte HLA-DR expression monitoring a useful tool to predict the risk of secondary infection?

Downregulation of the immune response is common among Intensive Care Unit (ICU) patients after an acute inflammatory injury, whether it was septic or not. Such a modification could be seen as an adaptation to attenuate the effects of the inflammatory storm on tissues, but it exposes the subject to the risk of nosocomial infection and impairs recovery processes. The intensity of immunity downregulation is difficult to characterize, since clinical presentation is silent and non-specific, which urges the use of tools for immune monitoring. This review focuses on the use of monocyte HLA-DR expression to detect immune hyporesponsiveness and to select the appropriate immunomodulating therapy, as well as the efficiency of this technique in controlling secondary infections.

Anti-inflammatory profile of circulating immune cells after surgery for seizure.

AIM: The central nervous system has been described as the coordinator of the inflammatory response to infection through the hypothalamo-pituitary axis and the autonomic nervous system. Brain lesions have been associated with impaired immunity and postoperative infections. We studied alterations of the inflammatory response in relation to neurohormonal patterns after neurosurgery for seizure. METHODS: Nine patients were studied before, during and immediately after operation, and then on days 1, 2 and 4 post-operatively. Monocyte HLA-DR (mHLA-DR) expression and plasma interleukin (IL)-10, IL-12 and MIF were measured ex vivo and after an in vitro 6-h our lipopolysaccharide (LPS) stimulation of whole blood. Corticotropin (ACTH), cortisol, arginine vasopressin, prolactin, epinephrine and norepinephrine were quantified in plasma. The effect of plasma mediators on LPS stimulation was studied by replacing plasma with standard culture medium. RESULTS: Surgery resulted in decreased ex vivo mHLA-DR expression, but no change in IL-10 or IL-12 plasma levels. mHLA-DR was low in LPS culture over the 4 postoperative days, whereas IL-10 release was increased and not counterbalanced by IL-12p40 production. The hormonal plasma pattern showed increased prolactin during anesthesia and peaks of cortisol, ACTH and arginine vasopressin during waking, but no alteration in catecholamine levels. mHLA-DR expression in LPS culture was not modified by plasma replacement, except immediately after surgery. CONCLUSION: Postoperatively, mHLA-DR expression was associated with an anti-inflammatory phenotype of whole blood. The anti-inflammatory profile was not related to the plasma mediators measured, suggesting that neural control might take place upstream in the circulation, at the level of progenitors in bone marrow.

Neurosurgery and elderly: analysis through the years.

The aging of the population in westernized countries constitutes an important issue for the health systems struggling with limited resources and increasing costs. Morbidity and mortality rates reported for neurosurgical procedures in the elderly vary widely. The lack of data on risk benefit ratios may result in challenging clinical decisions in this expanding group of patients. The aim of this paper is to analyze the elderly patients cohort undergoing neurosurgical procedures and any trend variations over time. The medical records of elderly patients (defined as an individual of 70 years of age and over) admitted to the Neurosurgical and Neuro-ICU Departments of a major University Hospital in Paris over a 25-year period were retrospectively reviewed. The analysis included: (1) number of admissions, (2) percentage of surgically treated patients, (3) type of procedures performed, (4) length of hospital stay, and (5) mortality. The analysis showed a progressive and significant increase in the proportion of elderly presenting for neurosurgical elective and/or emergency procedures over the last 25 years. The number of procedures on patients over 70 years of age increased significantly whereas the mortality dropped. Though the length of hospital stay was reduced, it remained significantly higher than the average stay. The types of procedures also changed over time with more craniotomies and endovascular procedures being performed. Age should not be considered as a contraindication for complex procedures in neurosurgery. However, downstream structures for postoperative elderly patients must be further developed to reduce the mean hospital stay in neurosurgical departments because this trend is likely to continue to grow.

Uncontrollable high-frequency tachypnea: a rare and nearly fatal complication of endoscopic third ventriculostomy: case report and literature review.

BACKGROUND: Endoscopic third ventriculostomy (ETV) is considered a safe procedure although it carries its rate of risks and complications that may occasionally be life-threatening. CASE REPORT: This is a report about a 48-year-old woman presenting with progressive gait unsteadiness, weakness of the lower extremities and cognitive impairment due to tri-ventricular hydrocephalus. This was treated with standard ETV. In the immediate post-operative period the patient developed a severe and uncontrollable tachypnea requiring sedation, intubation and mechanical ventilation. CONCLUSION: Tachypnea may be an early complication after standard ETV and although its mechanism remains yet unclear, we speculate that it may be related to excessive traction and/or surgical manipulation of the floor of the third ventricle. Supportive care with mechanical ventilation is the mainstay of treatment until spontaneous normalization of the respiratory mechanism occurs.

Expression of monocyte human leukocyte antigen-DR in relation with sepsis severity and plasma mediators.

AIM: After an initial septic hit, the immune response to a new antigen changes as time progresses, with an unpredictable efficiency. The aim of this study was to characterize the monocyte functional phenotype by HLA-DR expression in septic patients at the onset of sepsis and during recovery in relation to organ failure and plasma mediators. METHODS: Twenty-six patients were analyzed as either single organ failure at worst (SOF) or multiple organ failure (MOF) over 14 days. Twelve patients received immunosuppressive (IS) drugs before sepsis. We measured: 1) monocyte HLA-DR expression (mHLA-DR); 2) plasma pro-inflammatory mediators (IL-12p40, macrophage Migration Inhibitory Factor [MIF]); 3) plasma anti-inflammatory mediators (IL-10, cortisol); and 4) in vitro lipopolysaccharide (LPS) stimulated mHLA-DR in 6-hour whole blood culture or after plasma replacement with standard milieu. RESULTS: mHLA-DR expression was equally decreased in patients who were treated with IS drugs as those who were not. Despite the difference in severity, SOF patients showed a similar profound mHLA-DR downregulation as MOF patients at day 0, but tended to recover earlier. MOF patients presented higher plasma IL-10 and cortisol levels than SOF patients but similar plasma IL-12p40 and MIF levels. In vitro LPS stimulation showed an impaired mHLA-DR response in both groups. Plasma replacement by milieu elicited a slight improvement in the response to LPS in SOF but not MOF patients. CONCLUSIONS: At the onset of sepsis, an initial low mHLA-DR was not related to any prior IS drug regimen, the severity of the sepsis or the outcome. The duration of mHLA-DR downregulation could be related to plasma factors in SOF, while other mechanisms may be implicated in MOF evolution.

Cervical necrotizing fasciitis: 8-years' experience of microbiology.

Cervical necrotizing fasciitis (CNF) is a life-threatening complication of pharyngeal or dental infections. The aim of this paper was to investigate whether dental or pharyngeal source result from different pathogen(s) in CNF and whether antibiotics, given before admission, influence the antimicrobial resistance of pathogens. In 152 CNF patients, Streptococcus milleri group and Prevotella species were the predominant isolates, frequently copathogens, mostly in dental CNF samples. Penicillin and clindamycin resistance were observed in 39% and 37% of cases, respectively, independently of any previous antibiotic therapy. Thus, a combined aerobe-anaerobe infection may have a synergistic effect, which allows the infection to spread in cervical tissues.

A randomized study of out-of-hospital continuous positive airway pressure for acute cardiogenic pulmonary oedema: physiological and clinical effects.

AIMS: In acute cardiogenic pulmonary oedema (ACPE), continuous positive airway pressure (CPAP) added to medical treatment improves outcome. The present study was designed to assess the benefit of CPAP as a first line treatment of ACPE in the out-of-hospital environment. METHODS AND RESULTS: The protocol lasted 45 min, divided into three periods of 15 min. Patients with ACPE were randomly assigned in two groups: 1/Early CPAP (n = 63): CPAP alone (T0-T15); CPAP + medical treatment (T15-T30); medical treatment alone (T30-T45) and 2/Late CPAP (n = 61): medical treatment alone (T0-T15); medical treatment + CPAP (T15-T30); medical treatment alone (T30-T45). Primary endpoint: effect of early CPAP on a dyspnoea clinical score and on arterial blood gases. Secondary endpoints: incidence of tracheal intubation, inotropic support, and in-hospital mortality. T0-T15: CPAP alone had a greater effect than medical treatment on the clinical score (P = 0.0003) and on PaO(2) (P = 0.0003). T15-T30: adding CPAP to medical treatment (late CPAP group) improved clinical score and blood gases and the two groups were no longer different at T30. T30-T45: in both groups, CPAP withdrawal worsened clinical score. Six patients in 'early CPAP' group vs. 16 in 'late CPAP' group were intubated [P = 0.01, odds-ratio: OR = 0.30 (0.09-0.89)]. Dobutamine was used only in the 'late CPAP' group (n = 5), (P = 0.02). Hospital death was higher in 'late CPAP' group (n = 8) than in 'early CPAP' group (n = 2) [P = 0.05, OR = 0.22 (0.04-1.0)]. CONCLUSION: When compared to usual medical care, immediate application of CPAP alone in out-of-hospital treatment of ACPO is significantly better improving physiological variables and symptoms and significantly reduces tracheal intubation incidence and in-hospital mortality.

[Secondary ischaemic lesions: how to prevent?]. / Lésions ischémiques secondaires: comment les prévenir?

In addition to the initial lesions related to the brain injury, the final outcome depends also largely on the secondary ischaemic lesions. These lesions result from hypoperfusion whatever the mechanisms. It is then essential to detect early the conditions at risk of ischaemia, to be treated aggressively since the initial care. The multimodal monitoring is the only way to diagnose these conditions, to provide information about the mechanisms, and then to better adapt the treatment. Such an early detection helps to limit the consequences of the initial trauma, and may improve outcome.

Accelerated in vitro differentiation of blood monocytes into dendritic cells in human sepsis.

Summary Sepsis-induced immune depression is characterized by infection susceptibility and monocyte early deactivation. Because monocytes are precursors for dendritic cells (DC), alterations in their differentiation into DC may contribute to defective immune responses in septic patients. We therefore investigated the ability of monocytes to differentiate into functional DC in vitro in patients undergoing surgery for peritonitis. Monocytes from 20 patients collected immediately after surgery (D0), at week 1 and at weeks 3-4 and from 11 control donors were differentiated into immature DC. We determined the phenotype of monocytes and derived DC, and analysed the ability of DC to respond to microbial products and to elicit T cell responses in a mixed leucocyte reaction (MLR). We show that, although monocytes from septic patients were deactivated with decreased responses to lipopolysaccharide (LPS) and peptidoglycan and low human leucocyte antigen D-related (HLA-DR) expression, they expressed the co-stimulatory molecule CD80, CD40 and CCR7. Monocytes collected from patients at D0 and week 1 differentiated faster into DC with early loss of CD14 expression. Expression of HLA-DR increased dramatically in culture to reach control levels, as did responses of DC to LPS and peptidoglycan. However, although patient and control immature DC had similar abilities to induce T cell proliferation in MLR, maturation of DC derived from patients did not increase T cell responses. These results show that circulating monocytes from septic patients express markers of activation and/or differentiation despite functional deactivation, and differentiate rapidly into phenotypically normal DC. These DC fail, however, to increase their T cell activation abilities upon maturation.

Effects of hydroxyethyl starch administration on renal function in critically ill patients.

BACKGROUND: The influence of hydroxyethyl starch (HES) solutions on renal function is controversial. We investigated the effect of HES administration on renal function in critically ill patients enrolled in a large multicentre observational European study. METHODS: All adult patients admitted to the 198 participating intensive care units (ICUs) during a 15-day period were enrolled. Prospectively collected data included daily fluid administration, urine output, sequential organ failure assessment (SOFA) score, serum creatinine levels, and the need for renal replacement therapy (RRT) during the ICU stay. RESULTS: Of 3147 patients, 1075 (34%) received HES. Patients who received HES were older [mean (SD): 62 (SD 17) vs 60 (18) years, P = 0.022], more likely to be surgical admissions, had a higher incidence of haematological malignancy and heart failure, higher SAPS II [40.0 (17.0) vs 34.7 (16.9), P < 0.001] and SOFA [6.2 (3.7) vs 5.0 (3.9), P < 0.001] scores, and less likely to be receiving RRT (2 vs 4%, P < 0.001) than those who did not receive HES. The renal SOFA score increased significantly over the ICU stay independent of the type of fluid administered. Although more patients who received HES needed RRT than non-HES patients (11 vs 9%, P = 0.006), HES administration was not associated with an increased risk for subsequent RRT in a multivariable analysis [odds ratio (OR): 0.417, 95% confidence interval (CI): 0.05-3.27, P = 0.406]. Sepsis (OR: 2.03, 95% CI: 1.37-3.02, P < 0.001), cardiovascular failure (OR: 6.88, 95% CI: 4.49-10.56, P < 0.001), haematological cancer (OR: 2.83, 95% CI: 1.28-6.25, P = 0.01), and baseline renal SOFA scores > 1 (P < 0.01 for renal SOFA 2, 3, and 4 with renal SOFA = 0 as a reference) were all associated with a higher need for RRT. CONCLUSIONS: In this observational study, haematological cancer, the presence of sepsis, cardiovascular failure, and baseline renal function as assessed by the SOFA score were independent risk factors for the subsequent need for RRT in the ICU. The administration of HES had no influence on renal function or the need for RRT in the ICU.

[Severe cervical skin and soft tissue infections and necrotizing fasciitis]. / Dermohypodermites bactériennes nécrosantes et fasciites nécrosantes. Cellulites ORL.

Cervical severe skin and soft tissue infections and necrotizing fasciitis originate from dental or pharyngeal infections. When compared to other forms of skin and soft tissue infections, they are recognized late, usually after one week of evolution often in a patient receiving antibiotic treatments. Extensions toward adjacent anatomical structures including mediastinum lead to a life-threatening prognosis. The cutaneous appearance of these severe infections is usually inflammatory cervical signs combined to facial oedema. These moderate clinical signs require immediate surgery after CT scan imaging.