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Community-acquired pneumonia is a commonly diagnosed illness in which no causative organism is identified in half the cases. Application of molecular diagnostic techniques has the potential to lead to more targeted therapy in the face of increasing antibiotic resistance.

To determine the evolution of the outcome of patients with cirrhosis and septic shock.A 13-year (1998-2010) multicenter retrospective cohort study of prospectively collected data.The Collège des Utilisateurs des Bases des données en Réanimation (CUB-Réa) database recording data related to admissions in 32 ICUs in Paris area.Thirty-one thousand two hundred fifty-one patients with septic shock were analyzed; 2,383 (7.6%) had cirrhosis.None.Compared with noncirrhotic patients, patients with cirrhosis had higher Simplified Acute Physiology Score II (63.1 ± 22.7 vs 58.5 ± 22.8, p0.0001) and higher prevalence of renal (71.5% vs 54.8%, p0.0001) and neurological (26.1% vs 19.5%, p0.0001) dysfunctions. Over the study period, in-ICU and in-hospital mortality was higher in patients with cirrhosis (70.1% and 74.5%) compared with noncirrhotic patients (48.3% and 51.7%, p0.0001 for both comparisons). Cirrhosis was independently associated with an increased risk of death in ICU (adjusted odds ratio = 2.524 [2.279-2.795]). In patients with cirrhosis, factors independently associated with in-ICU mortality were as follows: admission for a medical reason, Simplified Acute Physiology Score II, mechanical ventilation, renal replacement therapy, spontaneous bacterial peritonitis, positive blood culture, and infection by fungus, whereas direct admission and admission during the most recent midterm period (2004-2010) were associated with a decreased risk of death. From 1998 to 2010, prevalence of septic shock in patients with cirrhosis increased from 8.64 to 15.67 per 1,000 admissions to ICU (p0.0001) and their in-ICU mortality decreased from 73.8% to 65.5% (p = 0.01) despite increasing Simplified Acute Physiology Score II. In-ICU mortality decreased from 84.7% to 68.5% for those patients placed under mechanical ventilation (p = 0.004) and from 91.2% to 78.4% for those who received renal replacement therapy (p = 0.04).The outcome of patients with cirrhosis and septic shock has markedly improved over time, akin to the noncirrhotic population. In 2010, the in-ICU survival rate was 35%, which now fully justifies to admit these patients to ICU.

Thenar eminence tissue oxygen saturation (StO(2)) was developed to assess organ perfusion. However, mottling, a strong predictor of mortality in septic shock, develops preferentially around the knee. We aimed to evaluate the prognostic value of StO(2) measured around the knee in septic shock patients and compare it to thenar StO(2).This was a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included. Parameters were recorded when vasopressors were started (H0) and every 6 h during 24 h. Their predictive value was assessed on 14-day mortality.Fifty-two patients were included. SOFA score was 11 (9-15) and SAPS II was 56 (40-72). At 6 h after ICU admission (H6), mean arterial pressure, cardiac index, and central venous pressure were not different between non-survivors and survivors; but non-survivors had higher arterial lactate level (8.8 ± 5.0 vs. 2.2 ± 1.5 mmol/l, P0.001), lower urinary output (0.22 ± 0.45 vs. 0.70 ± 0.50 ml/kg/h, P0.001) and ScvO(2) (62 ± 20 vs. 72 ± 9 %, P = 0.03). At H6, StO(2) was lower in non-survivors; this difference was not significant for thenar StO(2) (70 ± 15 vs. 77 ± 12 %, P = 0.10) but was very pronounced for knee StO(2) (39 ± 23 vs. 71 ± 12 %, P0.001). At H6, a low knee StO(2) was associated with a higher mottling score (P0.01), a higher lactate level (P0.002, R (2) = 0.2), and a lower urinary output (P = 0.02, R (2) = 0.12).After initial septic shock resuscitation, StO(2) measured around the knee is a strong predictive factor of 14-day mortality.

Background Little is known about the efficacy of management of iatrogenic pneumothoraces with small-bore chest tubes. The aim of this study was to assess the outcome of iatrogenic pneumothoraces requiring drainage managed with a small-bore chest tube and to compare the results to spontaneous pneumothoraces treated in the same unit with the same device. The primary outcome was requirement of video-assisted thoracoscopic surgery for drainage failure; secondary outcomes were length of drainage and number of inserted chest tubes. Methods Patients with pneumothorax admitted between 1997 and 2007 were retrospectively identified. Traumatic pneumothoraces and those occurring under mechanical ventilation were excluded. All pneumothoraces were drained using the same small-bore chest tube (8 French) according to our local protocol. Results Five hundred sixty-one pneumothoraces were analysed, 431 (76.8%) were spontaneous pneumothoraces and 130 (23.2%) were iatrogenic. Iatrogenic pneumothoraces were associated with less requirement of video-assisted thoracoscopic surgery for drainage failure [adjusted odds ratio= 0.24 (0.04, 0.86)]. Length of drainage of iatrogenic pneumothoraces was longer than for primary spontaneous pneumothoraces (3.8 ± 3.1 vs. 2.7 ± 1.8 days, P

Experimental and clinical studies have identified a crucial role of microcirculation impairment in severe infections. We hypothesized that mottling, a sign of microcirculation alterations, was correlated to survival during septic shock.We conducted a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included during a 7-month period. After initial resuscitation, we recorded hemodynamic parameters and analyzed their predictive value on mortality. The mottling score (from 0 to 5), based on mottling area extension from the knees to the periphery, was very reproducible, with an excellent agreement between independent observers [kappa = 0.87, 95% CI (0.72-0.97)].Sixty patients were included. The SOFA score was 11.5 (8.5-14.5), SAPS II was 59 (45-71) and the 14-day mortality rate 45% [95% CI (33-58)]. Six hours after inclusion, oliguria [OR 10.8 95% CI (2.9, 52.8), p = 0.001], arterial lactate level [1.5 OR 1; between 1.5 and 3 OR 3.8 (0.7-29.5);3 OR 9.6 (2.1-70.6), p = 0.01] and mottling score [score 0-1 OR 1; score 2-3 OR 16, 95% CI (4-81); score 4-5 OR 74, 95% CI (11-1,568), p0.0001] were strongly associated with 14-day mortality, whereas the mean arterial pressure, central venous pressure and cardiac index were not. The higher the mottling score was, the earlier death occurred (p0.0001). Patients whose mottling score decreased during the resuscitation period had a better prognosis (14-day mortality 77 vs. 12%, p = 0.0005).The mottling score is reproducible and easy to evaluate at the bedside. The mottling score as well as its variation during resuscitation is a strong predictor of 14-day survival in patients with septic shock.

Complicated abdominal aortic aneurysm (AAA) is a major cause of mortality in elderly men. Ang II-dependent TGF-beta activity promotes aortic aneurysm progression in experimental Marfan syndrome. However, the role of TGF-beta in experimental models of AAA has not been comprehensively assessed. Here, we show that systemic neutralization of TGF-beta activity breaks the resistance of normocholesterolemic C57BL/6 mice to Ang II-induced AAA formation and markedly increases their susceptibility to the disease. These aneurysms displayed a large spectrum of complications on echography, including fissuration, double channel formation, and rupture, leading to death from aneurysm complications. The disease was refractory to inhibition of IFN-gamma, IL-4, IL-6, or TNF-alpha signaling. Genetic deletion of T and B cells or inhibition of the CX3CR1 pathway resulted in partial protection. Interestingly, neutralization of TGF-beta activity enhanced monocyte invasiveness, and monocyte depletion markedly inhibited aneurysm progression and complications. Finally, TGF-beta neutralization increased MMP-12 activity, and MMP-12 deficiency prevented aneurysm rupture. These results clearly identify a critical role for TGF-beta in the taming of the innate immune response and the preservation of vessel integrity in C57BL/6 mice, which contrasts with its reported pathogenic role in Marfan syndrome.

Three women were consecutively admitted to our medical intensive care unit for thyrotoxicosis after the ingestion of dietary pills accidentally containing high levels of thyroxin. These cases were observed during an outbreak in the Paris area. Despite similar blood levels of thyroid hormones, their clinical presentation and outcome were very different. One patient developed febrile confusion and died from malignant hyperthermia. The second one had progressive confusion requiring mechanical plasma exchange therapy and had a favorable outcome. The third one had very moderate symptoms. These exceptional observations raise several issues concerning diagnosis, physiopathology and treatment of thyrotoxicosis factitia.

Background: Fluid therapy induces haemodilution related to plasma volume expansion. The aim of our study was to compare haemodilution after a single hydroxyethyl starches (HES) 130/0.4 infusion in two groups of patients, one with and one without sepsis. We hypothesized that a single HES challenge would induce similar sustained haemodilution in both groups. Methods: In this prospective preliminary study, patients predicted to require a single further volume-expander infusion were included immediately before receiving 500 ml of 6% HES 130/0.4 over a 15-min period. No additional fluid was administered over the next 8 h. Haematocrit, and serum albumin and protein were determined immediately before HES infusion then after 1, 2, 3, 4, and 8 h. Results: Twelve patients were included in each group. In both groups, all three haemodilution markers had significantly lower values after 1 h than at baseline. None of the values after 1 and 3 h differed significantly between the two groups. Neither did any of the other study variables show significant differences between the groups with and without sepsis. Conclusion: We found that a starch-based compound was as effective in inducing haemodilution in patients with sepsis as in controls without sepsis, suggesting that HES may remain within the intravascular space even in patients with sepsis. Haemodilution parameters such as haematocrit, serum albumin and serum protein are useful for assessing the duration of plasma volume expansion induced by fluid therapy in critically ill patients.

Although the demographic characteristics of patients who develop infective endocarditis (IE) have changed over the last few decades, Enterobacteriaceae remain rarely responsible. We report the clinical and epidemiological characteristics of 9 patients with native-valve Enterobacteriaceae IE from 6 French medical intensive care units over a 10-y period and have identified 29 additional cases in the literature. Nearly a third of the 38 patients were immunocompromised and/or had previously known valvular heart disease. Salmonella spp. and Yersinia spp. were the most frequently isolated microorganisms reported in the literature. The overall mortality rate was 24% (9/38) and was lower for operated patients (10% (1/10)) compared to those who did not undergo valve surgery (31% (8/26)). Our results confirmed the rarity of native-valve endocarditis caused by Enterobacteriaceae, pathogens frequently responsible for nosocomial and community-acquired bacteraemias. This paradox may be explained by susceptibility to the bactericidal action of serum and the inability of these bacteria to colonize the endocardium.

OBJECTIVE: Upper gastrointestinal bleeding (UGIB) related to stress ulcers was formerly a fearsome complication of intensive care. The incidence of this event has decreased over the years. However, the morbidity, mortality, and causes of UGIB, particularly the etiologic role of Helicobacter pylori infection, are still controversial. Therefore, we prospectively assessed the incidence of UGIB in the intensive care unit (ICU) and evaluated the role of H. pylori infection. DESIGN: A prospective observational study followed by a case-control study. SETTING: Seven ICUs in the Paris area, five of them located in teaching hospitals. PATIENTS: All patients admitted consecutively to seven ICUs during a 1-year period were monitored for signs of clinically relevant UGIB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Only cases of endoscopically confirmed UGIB were analyzed. Patients whose hemorrhage originated from the stomach and/or duodenum were tested for H. pylori infection, by means of serology, histologic examination, and stool antigen detection. The possible association between H. pylori and UGIB was examined in a case-control study. Twenty-nine of the 4,341 patients admitted to the seven ICUs during the study period had clinically relevant, endoscopically confirmed UGIB (incidence, 0.67%; 95% confidence interval, 0.56%-0.77%). Ulcers were most frequently observed endoscopically. Patients who bled had a higher Simplified Acute Physiology Score (SAPS II) at admission (mean +/- sd, 47 +/- 14 vs. 36 +/- 28; p < .001). Despite a higher in-ICU mortality rate among patients who bled (73% vs. 16%; p < .001), death was never due to bleeding. H. pylori infection was more frequent in patients who bled than in matched controls (36% vs. 16%; p = .04). CONCLUSIONS: Clinically relevant, endoscopically confirmed UGIB is a rare event in the ICU setting and tends to occur in severely ill patients. H. pylori infection is more frequent in patients with gastroduodenal hemorrhage than in nonbleeding patients.

To determine the prognostic indicators of long-term survival after admission to a medical intensive care unit (MICU) for patients aged 80 years and over. DESIGN. Prospective cohort study.A 14-bed MICU in a 970-bed, acute care, tertiary, university hospital in Paris, France.A total of 233 patients aged 80 years and over discharged from a MICU during a 2-year period.Severity at admission was estimated using the Simplified Acute Physiology Score. The underlying condition was classified using the MacCabe classification. The functional status was assessed using the Knaus classification. The outcome after MICU discharge was determined after a median 2-year follow-up. The functional outcome was assessed by telephone interviews, employing the Instrumental Activities of Daily Living (IADL). The in-MICU mortality was 19.5% including death occurring during the 2 days following discharge. The long-term survival rates for patients admitted to the MICU were 59% at 2 months, 33% at 2 years, and 29% at 3 years. The multivariate analysis identified two prognostic factors of death after discharge: presence of an underlying fatal disease (HR 1.7; 95% CI 1.1-2.6) and severe functional limitation (HR 1.7; 95% CI 1.2-2.6). The IADL was excellent or good for 56% of the surviving patients.Long-term survival after MICU is mainly related to the underlying condition, whereas known factors for in-MICU survival do not influence long-term prognosis.

The presence of circulating endotoxin is common during sepsis but its prognostic value is poor. We hypothesized that this lack of correlation with outcome could be related in part to the presence of circulating antiendotoxin antibodies. In a 14-bed medical intensive care unit, in an 821-bed tertiary teaching hospital, we prospectively assessed endotoxin and antiendotoxin antibodies in patients with severe sepsis or septic shock. Blood samples for the determination of circulating endotoxin and antiendotoxin antibodies were drawn when severe sepsis or septic shock were diagnosed (day 0) and then on day 1, day 2, and day 4. Daily measurements of antiendotoxin antibodies did not discriminate survivors from nonsurvivors. No antibody depletion was observed. However, during follow-up, the antiendotoxin immunoglobulin (Ig)M antibody level increased among survivors but decreased among nonsurvivors (51.2 vs −44.8 MU/mL, P = .007). Circulating endotoxin was detectable among 9 of 17 patients on inclusion but neither the basal value nor sequential measurements correlated with outcome. These results suggest that during severe sepsis and septic shock, circulating endotoxin is a poor prognostic marker whereas the detection of an increase in IgM antiendotoxin antibody levels could identify survivors. This increase in IgM antibody levels could be attributed to a reactivation of the immune system. © Elsevier Inc. All rights reserved.

Life-threatening bleeding in four patients with an unusual excessive response to dabigatran: Implications for emergency surgery and resuscitation

Background In critically ill patients with pneumonia, accurate microorganism identification allows appropriate antibiotic treatment. In patients undergoing bronchoalveolar lavage (BAL), direct examination of the fluid using Gram staining provides prompt information but pathogen identification accuracy is low. Culture of BAL fluid is actually the reference, but it is not available before 24 to 48 h. In addition, pathogen identification rate observed with direct examination and culture is decreased when antibiotic therapy has been given prior to sampling. We therefore assessed, in critically ill patients with suspected pneumonia, the performance of a multiplex PCR (MPCR) to identify pathogens in BAL fluid. This study is a prospective pilot observation. Methods We used a MPCR detecting 20 types of microorganisms. Direct examination, culture, and MPCR were performed on BAL fluid of critically ill patients with pneumonia suspicion. The final diagnosis of infective pneumonia was retained after the medical chart was reviewed by two experts. Pathogen identification rate of direct examination, culture, and MPCR in patients with confirmed pneumonia was compared. Results Among the 65 patients with pneumonia suspicion, the diagnosis of pneumonia was finally retained in 53 cases. Twenty nine (55%) were community-acquired pneumonia and 24 (45%) were hospital acquired. Pathogen identification rate with MPCR (66%) was greater than with culture (40%) and direct examination (23%) (p =0.01 and p p p p Conclusions The results of this pilot study suggest that in critically ill patients, MPCR performed on BAL fluid could provide higher identification rate of pathogens involved in pneumonia than direct examination and culture, especially in patients having received antimicrobial treatment.

Objective: To identify parameters thatindicate retained secretions and the need for tracheal suctioning (TS)in patients receiving mechanical ventilation (MV). Design: Prospective observational study. Setting: A 14-bed medical ICU in a 946-bed universityhospital. Patients: Sixty-six consecutive patientsreceiving MV. Interventions: Two successive trachealsuctions, TS1 and TS2, performed at a 2-h interval as usual patientcare. Retained secretions were considered significant if the volume of secretions removed by TS2 was > 0.5 mL. Measurementsand results: Variations between TS1 and TS2 of pulse oximetricsaturation (Sp o 2 ), peak inspiratory pressure(Ppeak), tidal volume (V t ), and Ramsay score were comparedbetween patients with TS2 ≤ 0.5 mL (group 1; n = 27) and patientswith TS2 > 0.5 mL (group 2; n = 39). The presence of a sawtoothpattern on flow-volume loop displayed on the monitor screen of theventilator and of respiratory sounds heard over the trachea before TS2were compared between the two groups. Variations of Ppeak, V t , Sp o 2 , and Ramsay score betweenTS1 and TS2 did not differ between the two groups. However, group 2 hada sawtooth pattern (82% vs 29.6%; p = 0.0001) and respiratorysounds (66.6% vs 25.9%; p = 0.001) more frequently than group 1before TS2. For the sawtooth pattern, the likelihood ratio (LR) of apositive test was 2.70 and the LR of a negative test was 0.25, whilefor respiratory sounds it was 2.50 and 0.45, respectively. When thepresence of a sawtooth pattern and of respiratory sounds was combined, the LR of a positive test rose to 14.7 and the LR of a negative testwas 0.42. Conclusions: A sawtooth pattern and/orrespiratory sounds over the trachea are good indicators of retainedsecretions in patients receiving MV and may indicate the need for TS. Conversely, the absence of a sawtooth pattern may rule out retainedsecretions.

Resume La necrose corticale renale bilaterale est une cause tres rare d'insuffisance renale aigue qui a ete surtout rapporte a des causes obstetricales dans les annees 1970. Nous rapportons ici le premier cas de necrose corticale bilaterale lie a un syndrome des antiphospholipides (SAPL) paraneoplasique.

Acute bilateral renal cortical necrosis is a very rare cause of acute renal failure. We report here for the first time a case related to antiphospholipid syndrome, paraneoplastic of a lung neoplasia. A 46-year-old male smoker without medical history was admitted for acute dyspnea and anuria. Biological examination showed acute renal failure associated with hyperkalemia, high serum lactate dehydrogenase level, and prolonged activated thrombin time (ratio 1.29). Chest radiograph showed a right laterotracheal round lesion. A percutaneous left renal biopsy showed cortical necrosis, and renal arteriography confirmed bilateral cortical necrosis. Blood examination showed antiphospholipid antibodies type anticardiolipin. Chest computed tomographic scan confirmed the presence of a lung tumor. Two years after tumor surgery, the patient was still anuric and on long-term hemodialysis therapy, but antiphospholipid antibody results were negative. This case describes the first association of antiphospholipid syndrome to epidermoid lung cancer, shown by cortical bilateral necrosis. It also emphasizes the utility of renal biopsy in case of an unusual acute renal failure.

SummaryThe aim of the study was to identify the predictors of brain death (BD) uponadmission to the intensive care unit (ICU) of comatose patients with spontaneousintracerebral hemorrhage (ICH). Patients admitted in our ICU from 2002 to 2010for spontaneous ICH and placed under mechanical ventilation were retrospec-tively analyzed. Of the 72 patients, 49% evolved to BD, 39% died after withdrawalof life support, and 12% were discharged alive. The most discriminating charac-teristics to predict BD were included in two models; Model 1 contained 3 abol-ished brainstem responses [adjusted odds ratios (OR) = 8.4 (2.4, 29.1)] and theswirl sign on the baseline CT-scan [adjusted OR = 5.0 (1.6, 15.9)] and Model 2addressed the abolition of corneal reflexes [unilateral/bilateral: adjusted OR = 4.2(0.9, 20.1)/8.8 (2.4, 32.3)] and the swirl sign on the baseline CT-scan [adjustedOR = 6.2 (1.9, 20.0)]. Two scores predicting BD were created (sensitivity: 0.89and 0.88, specificity: 0.68 and 0.65). Risk of evolution toward BD was classified aslow (corneal reflexes present and no swirl sign), high ( 1 corneal reflexes abol-ished and swirl sign), and intermediate. Simple signs at ICU admission can pre-dict BD in comatose patients with ICH and could increase the potential for organdonation.IntroductionEarly prediction of evolution toward brain death (BD) incomatose patients with stroke is of great interest as BD iscurrently in France the primary source of organ donation(80%) [1,2]. Recently, the recommendations of Frenchsocieties regarding stroke management outlined that coma-tose patients with stroke and very bad prognosis could ethi-cally be admitted to ICU if evolution toward BD, allowinga potential organ donation, seems likely [3]. However, todate, no accurate criteria predicting evolution toward BDin comatose patients with stroke has been reported.Spontaneous intracerebral hemorrhage (ICH) is thedeadliest type of stroke and is a leading cause of mortalityand morbidity worldwide [4–7]. The two main causes ofdeath after ICH admitted to ICU are withdrawal of life sup-port for perceived futility of care and BD [8–10]. Althoughmany studies have evaluated early predictors of neurologi-cal outcomes after ICH, none specifically sought to iden-tify predictors of BD. Most of these studies pooled the

Study objectives To study circulatory endotoxin (ET) in patients with sepsis syndrome ( SS ) in order to answer three questions: (a) How often and at which concentration is ET present in the plasma of patients with SS and is the presence of ET a prognostic marker in this situation? (b) Is detection of ET helpful in predicting Gram-negative bacterial infections with or without bacteremia? (c) What are the kinetics of clearance of ET concentrations in plasma? Design Prospective study of consecutive patients fulfilling Bone's criteria for SS. Setting Medical ICU in a teaching hospital. Patients The study included 93 patients. The simplified acute physiologic score was 19±6, 49 percent were in shock, and 54 percent were mechanically ventilated. The mortality at day 28 was 53 percent. Measurements Endotoxin determinations and blood cultures were performed simultaneously at the onset (day 1) of SS. Samples were collected on several days from 48 patients. Endotoxin concentration was determined using an end point chromogenic Limulus assay. For the first ET determination, the mean circulatory level (mean±SEM) was calculated among patients with detectable ET, thus excluding patients with a null value for ET. Results On day 1, ET was detected in 44 patients (47 percent; 60.2±16.5 pg/ml) and was statistically more frequent in patients with shock, elevated plasma lactate, and organ failure. There was no statistical difference for age, gender, ratio of PaO 2 to fraction of inspired oxygen. Among patients with proven Gram-negative bacterial infection (n = 46), ET was detected in 67 percent as compared with 28 percent without Gram-negative bacterial infection (p = 0.0001). On day 1, among 19 patients who had positive blood cultures with Gram-negative bacteria (GNB), 15 had detectable ET (79 percent, 61±22 pg/ml). In 14 other patients whose blood cultures were positive for GNB but became negative on day 1, 9 had detectable ET (64 percent; 36±6.5 pg/ml). Endotoxin declined linearly between days 1 and 4. Conclusion In our study, the plasma ET concentration predicts neither Gram-negative infection, with or without bacteremia, nor the outcome. However, when ET is present in the plasma of patients with SS it remains detectable for a long period of time as compared to its rapid disappearance from plasma of animals or healthy human volunteers receiving ET intravenously. This slow clearance of ET suggests either a continuous release or a defect in its clearance.

Severe infections caused by hypermucoviscous Klebsiella pneumoniae have been reported in Southeast Asian countries over the past several decades. This report shows their emergence in France, with 12 cases observed during a 2-year period in two university hospitals. Two clones (sequence type 86 [ST86] and ST380) of serotype K2 caused five rapidly fatal bacteremia cases, three of which were associated with pneumonia, whereas seven liver abscess cases were caused by K1 strains of ST23.

The mortality rate among patients with human immunodeficiency virus (HIV) requiring mechanical ventilation (MV) for acute respiratory failure (ARF) secondary to Pneumocystis carinii pneumonia (PCP) is still a matter of discussion. For some authors, it is in the 50 percent range, while for others the prognosis is grim, with virtually no survivors. The aim of this retrospective study conducted between January 1987 and January 1992 was to analyze the outcome of such patients. We studied 33 patients, 29 men and 4 women (38.6 +/- 9.9 years, 21 homosexuals, 8 intravenous drug users, 3 transfusion related, 1 heterosexual) infected by HIV for at least 19.7 +/- 21.6 months. It was the first PCP episode in all but 2 patients and the diagnosis was made by bronchoalveolar lavage (n = 32) or lung biopsy specimen (n = 1). Only three patients were receiving primary prophylaxis for PCP (trimethoprim-sulfamethoxazole [TMP-SMZ], n = 2; pentamidine, n = 1). Pneumocystis carinii pneumonia was the first manifestation of AIDS in nine patients. The duration of symptoms prior to treatment was 19.6 +/- 11.3 days. At the time of hospital admission, laboratory findings were as follows: PaO2 = 40.7 +/- 7.8 mm Hg on room air; serum LDH = 1,172 +/- 792 IU/L; T4 cell count = 60.2 +/- 67/mm3. Mechanical ventilation was always required for ARF, which was never induced by bronchoscopy. The interval between treatment and MV was 8.1 +/- 6.5 days and the duration of MV was 11.4 +/- 9.9 days. The patients were classified into 3 groups on the basis of the duration and type of treatment before MV, as follows: group 1, n = 10: TMP-SMZ (20-100 mg/kg) IV and methylprednisolone (MP) or = 5 days and MP or = 5 days before MV. (The MP dose was as follows: 240 mg/d once a day from day 1 to day 3; 120 mg/d from day 4 to day 6; and 60 mg/d from day 7 to day 9.) Despite MV, TMP-SMZ, and MP, death secondary to PCP-related ARF occurred in 81.9 percent of patients, 20 +/- 4.8 days after the beginning of treatment and 11.4 +/- 9.9 days after the beginning of MV. Six patients survived, five in group 1 and one in group 3.(ABSTRACT TRUNCATED AT 400 WORDS)

We evaluated ultrasonic examination as a diagnostic tool for catheter misplacement and pneumothorax after central venous catheter insertion. Physicians in the intensive care unit (ICU) performed the ultrasonic examinations, and the results were compared with those of chest radiography. Eighty-five central venous catheters (70 subclavian and 15 internal jugular) were inserted into 81 patients; 10 misplacements and one pneumothorax occurred. Ultrasonic examination feasibility was 99.6%. The only pneumothorax and all misplacements except one were diagnosed by ultrasound. Taking into consideration misplacements and pneumothorax research, ultrasonic examination did not give any false positive results. The mean time of the entire ultrasonic examination was 6.8 +/- 3.5 min, whereas 80.3 +/- 66.7 min were needed for the radiography (p < 0.0001). This study has suggested that ultrasonic diagnosis of catheter misplacement and pneumothorax related to central venous catheterization is a rapid and accurate method that can be easily performed by ICU physicians.

Background Pleural ultrasonography (PU) is more sensitive than chest radiograph (CXR) for diagnosing pneumothorax and could be useful for detecting resolution of pneumothorax after drainage. The aim of this prospective double-blind observational study was to assess PU accuracy during pneumothorax follow-up after drainage. Methods All patients hospitalized with pneumothorax requiring drainage were eligible. After drainage, residual pneumothorax was assessed by CXR and PU (1) 24 h after bubbling in the aspiration device had stopped, (2) 6 h after clamping the pleural catheter, and (3) 6 h after removing the pleural catheter. Pneumothorax indicated by PU but not CXR was confirmed by CT scan or by aspiration of > 10 mL of air. Results Forty-four unilateral pneumothoraces were studied (primary spontaneous: 70.5%), and 162 pairs of examinations (CXR and PU) were performed. Twenty residual pneumothoraces were detected by both CXR and PU. Furthermore, PU suspected 14 pneumothoraces that were not identified by CXR; 13 were confirmed. All of these pneumothoraces resulted in therapeutic intervention. Thus, 39% (13/33) of the confirmed residual pneumothoraces were missed by CXR. In patients with primary spontaneous pneumothorax, the positive predictive value of PU for residual pneumothorax diagnosis was 100%; for other pneumothoraces, this value ranged from 90% in the absence of a lung point to 100% when a lung point was observed. PU results were obtained faster than results from CXR (35 ± 34 min vs 71 ± 56 min, P Conclusions The accuracy of PU is excellent for detecting residual pneumothorax during pneumothorax follow-up after drainage.

The endothelium is a highly dynamic cell layer that is involved in a multitude of physiological functions, including the control of vascular tone, the movement of cells and nutrients, the maintenance of blood fluidity and the growth of new vessels. During severe sepsis, the endothelium becomes proadhesive, procoagulant, antifibrinolytic and is characterized by alterations of vasomotor regulation. Most of these functions have been discovered using in vitro and animal models, but in vivo exploration of endothelium in patients remains difficult. New tools to analyze endothelial dysfunction at bedside have to be developed.

Herpes simplex virus hepatitis (HSV hepatitis) is an uncommon and severe complication of HSV type 1 and HSV type 2 infection. HSV hepatitis affects mostly immunocompromised patients. We report the case of a young man without any previous known immunodeficiency who developed fatal HSV hepatitis in the first 8 days of oral corticotherapy given for ulcerative colitis. A prompt diagnosis was possible because HSV was recovered from peripheral blood leukocytes.

To evaluate limited training of ICU physicians without knowledge of ultrasound in performing basic general ultrasonography.A prospective, observational, study conducted in a 14-bed MICU.Seventy-seven critically ill patients (38 females) aged 64 +/- 16 years, with a SAPS II score of 47 +/- 21, 49 of whom (64%) were receiving mechanical ventilation.After 8.5 h of training comprising a 2.5 h didactic course that included essential views of normal and pathologic conditions and three hands-on sessions of 2 h each, one of eight ICU residents and the radiologist on duty performed the same examination in a blind manner. The questions addressed concerned the presence of pleural effusion, intra-abdominal effusion, acute cholecystitis, intrahepatic biliary duct dilation, obstructive uropathy, chronic renal disease, and deep venous thrombosis.The answers to 129 questions were analyzed. The possible presence of pleural effusion, and arguments for the presence of urinary tract obstruction and chronic renal insufficiency, were the questions most frequently addressed. Residents answered 84.4% of the questions correctly [Kappa: 0.66, CI 95% (0.32-1.12)]. Most of the discrepancies concerned small non-drainable pleural or abdominal effusions. For questions with a potential therapeutic impact, residents answered 95% of the questions correctly [Kappa 0.86, CI 95% (0.75-1.04)]. Residents completed the examination in 37 +/- 39 min compared with 296 +/- 487 min for the radiologists (P = 0.004).These results suggest that after brief focused training, intensive-care unit physicians without previous knowledge of ultrasonography can competently perform basic general ultrasonic examinations.

Resume Nous rapportons les resultats retrospectifs du drainage percutane des pneumothorax compliquant la pneumocystose pulmonaire, chez 12 malades atteints du SIDA. Le drainage a ete efficace deux fois. Parmi les 10 malades ayant une fistule persistante, deux sont decedes et le poumon s'est recolle spontanement dans un cas. Les sept autres ont eu un pneumothorax controlateral et ont subi une pleurectomie chirurgicale unilaterale. Deux fois la chirurgie a ete un succes. Trois malades sont decedes en postoperatoire, et 2 autres ont eu un decollement persistant minime. Parmi les malades decedes, quatre avaient un pneumothorax initial bien tolere. Pour tenter de limiter la mortalite liee au traitement de ces pneumothorax compliquant la pneumocystose pulmonaire, nous pensons que les pneumothorax peu symptomatiques pourraient ne pas etre draines. Si une thoracotomie est decidee pour une fistule persistante, un scanner preoperatoire permettrait de recherche des lesions bulleuses controlaterales susceptibles de justifier un geste chirurgical bilateral.

Accumulation of nondiffusible solutes in plasma leads to redistribution hyponatremia with an increased osmolar gap (i.e., the difference between measured and calculated osmolality). In critically ill patients, intracellular solutes may leak out of the cell because of an increased membrane permeability and may lead to redistribution hyponatremia with increased osmolar gap, a concept called the "sick cell syndrome." The aims of this prospective study were to determine whether an increased osmolar gap related to endogenous solutes accumulation was present in intensive care patients with true hyponatremia and to identify the solutes accounting for this increased osmolar gap.A 14-bed medical intensive care unit in an 821-bed university hospital.A 20-wk prospective observational study.Fifty-five consecutive patients with a measured plasma sodium concentrationor=130 mmol/L (mean +/- sd, 126 +/- 6 mmol/L) were automatically identified by the Biochemistry Department. Patients were excluded in the case of reduced plasma water content resulting from hyperlipidemia or hyperproteinemia, in the case of hyperglycemia, or if exogenous compounds known to increase the osmolar gap were present.Plasma osmolar gap was calculated.Plasma osmolar gap was considered significant if10 mosm/kg. Total plasma amino acid concentration also was measured. Organ dysfunctions were assessed with the Sequential Organ Failure Assessment. Thirty of the 55 patients (54%) had an osmolar gap10 mosm/kg (17.2 +/- 7.1 mosm/kg). Sequential Organ Failure Assessment score was significantly higher in the osmolar gap patients (6.4 +/- 3.2 vs. 4.5 +/- 2.0; p =.015). No difference of amino acids concentration was observed between osmolar gap and non-osmolar gap patients, and no correlation was observed between osmolar gap and amino acid concentration. Accumulation of ketone bodies and lactic acid was also unlikely. During correction of hyponatremia in osmolar gap patients, a significant decrease of plasma osmolar gap was observed and a statistically significant inverse relationship was demonstrated between osmolar gap decrease and plasma sodium concentration increase.Hyponatremia with increased osmolar gap related to endogenous solutes accumulation is observed frequently in hyponatremic intensive care patients, especially in patients with the most severe organ dysfunctions. The nature of the endogenous solutes accounting for the increased osmolar gap remains to be determined. Simultaneous correction of sodium and osmolar gap suggests a causal link between increased osmolar gap and hyponatremia and may support the concept of sick cell syndrome.

A 79 year-old patient with prostate cancer related Cushing's syndrome was referred to ICU for acute respiratory distress occurring two days after introduction of mifepristone. Pneumocystis jirovecii pneumonia was diagnosed. Despite anti pneumocystis therapy and supportive treatment, the patient died of multiple organ failure. The relationship between mifepristone and Cushing's syndrome and potential implications are discussed. Cushing's syndrome is a classical but rare disease resulting from exposure to excessive concentrations of glucocorticoid. When surgery is not feasible medical therapy should be discussed. A 79 year-old man was admitted to intensive care unit for acute respiratory distress. He had been treated for prostate cancer for 12 years, with radiotherapy and hormonotherapy. The last prostate-specific antigen (PSA) level was (0, 24 ng/ml) while pelvis MRI disclosed irregular prostate consistent with radiotherapy after-effects without any sign of recurrence of malignancy. He was referred 3 months before to the general ward because of depression, severe systemic hypertension, hypokalaemia and diabetes mellitus. Endogenous hypercortisolism was diagnosed. Static and dynamic analysis: (plasma cortisol level at 8 am : 1564 nmol/l (normal

The case of a 68-year-old man suffering from pneumococcal meningoencephalitis is reported. Antibacterial susceptibility tests revealed a multiply resistant pneumococcal strain. High doses of cefotaxime were necessary to sterilize the cerebrospinal fluid despite the achievement of a satisfactory level of antibiotic in the cerebrospinal fluid with moderate dosage. In France, as well as in many countries, high doses of third-generation cephalosporins such as cefotaxime or ceftriaxone should be administered for the initial therapy of suspected pneumococcal meningitis.

The impact of antibiotics on total endotoxemia and circulating tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-8 in 18 patients with severe bacteremic sepsis or septic shock due to gram-negative species was investigated. Endotoxemia, TNF-alpha, IL-6, and IL-8 were assayed before (H0) and 1 h (H1) and 4 h (H4) after the first antibiotic infusion. Endotoxemia decreased from H0 (median, 0.4 EU/mL; interquartile interval, 0.09-1.23) to H1 (median, 0.19 EU/mL; interquartile interval, 0.07-0.75; P = .03) and remained stable between H1 and H4 (median, 0.12 EU/mL; interquartile interval, 0.09-0.30; P = .4). IL-6 levels fell between H0 and H4 (P = .01) and between H1 and H4 (P = .03). IL-8 was higher at H0 than at H1 (P = .04) and at H4 (P = .01). These results suggest that endotoxemia is not increased by antibiotherapy of severe gram-negative bacteremia.

A 71-year-old woman with a history of hyperten-sion and restrictive chronic respiratory failure wasadmitted to our intensive care unit (ICU) for dyspnoea.She had been on levofloxacin for 3 weeks forpneumonia, and had purulent expectoration, fever(38.5 C) and pulmonary crepitations, but no signs ofhaemodynamic failure or hypersensitivity. Antibio-therapy was initiated empirically, with piperacillin,tazobactamandamikacin(10mg/kgonce),andafter48hours also vancomycin (2g/day), based on a bloodculture positive for meticillin resistant Staphylococcusaureus. After 3 days, her laboratory tests showed:serum creatinine, 396mmol/l (75mmol/l at admission);no hypereosinophilia, vancomycin residual bloodlevel 47.8mg/l (normal 20 to 30mg/l). A renal echog-raphy ruled out an obstructive uropathy. Urinetests suggested an organic acute renal failure (ARF)(natriuresis/kaliuresis

Introduction The interdependence between endotoxemia, gram negative (GN) bacteremia and mortality has been extensively studied. Underlying patient risk and GN bacteremia types are possible confounders of the relationship. Methods Published studies with ≥10 patients in either ICU or non-ICU settings, endotoxemia detection by limulus assay, reporting mortality proportions and ≥1 GN bacteremia were included. Summary odds ratios (OR) for mortality were derived across all studies by meta-analysis for the following contrasts: sub-groups with either endotoxemia (group three), GN bacteremia (group two) or both (group one) each versus the group with neither detected (group four; reference group). The mortality proportion for group four is the proxy measure of study level risk within L'Abbé plots. Results Thirty-five studies were found. Among nine studies in an ICU setting, the OR for mortality was borderline (OR

Background: We assessed the potential impact of infusion tubing on blood glucose imbalance in ICU patients given intensive insulin therapy (IIT). We compared the incidence of blood glucose imbalance in patients equipped, in a nonrandomized fashion, with either conventional tubing or with a multiport infusion device. Methods: We retrospectively analyzed the nursing files of 35 patients given IIT through the distal line of a doublelumen central venous catheter. A total of 1389 hours of IIT were analyzed for occurrence of hypoglycemic events [defined as arterial blood glucose below 90 mg/dL requiring discontinuation of insulin]. Results: Twenty-one hypoglycemic events were noted (density of incidence 15 for 1000 hours of ITT). In 17 of these 21 events (81%), medication had been administered during the previous hour through the line connected to the distal lumen of the catheter. Conventional tubing use was associated with a higher density of incidence of hypoglycemic events than multiport infusion device use (23 vs. 2 for 1,000 hours of IIT; rate ratio = 11.5; 95% confidence interval, 2.71–48.8; p < 0.001). Conclusions: The administration of on-demand medication through tubing carrying other medications can lead to the delivery of significant amounts of unscheduled products. Hypoglycaemia observed during IIT could be related to this phenomenon. The use of a multiport infusion device with a limited dead volume could limit hypoglycemia in patients on IIT.

We describe a case of air cyst lesions in an AIDS patient suffering from Pneumocystis carinii pneumonia. This case is unique because these lesions were generalized to both lungs and initially well tolerated. Pathologic examination revealed extensive tissue invasion by P carinii. The prognosis was complicated by bilateral pneumothoraces. Surgical right pleurodesis allowed lung re-expansion but did not prevent recurrence of fatal contralateral pneumothorax.

During the adult respiratory distress syndrome (ARDS), an irreversible fibrotic process can occur extremely rapidly. To establish indices of ARDS in pneumonia as well as the severity of the lung fibrosis, we have undertaken for the first time a study of four markers of collagen metabolism obtained from both bronchoalveolar lavage fluid (BALF) and serum: Type I (CI), Type III (CIII), N-terminal peptide of Type III procollagen (PIIINP), and galactosylhydroxylysylglucosyltransferase activity (GGT). We studied 61 patients (13 coma controls, 29 with pneumonia, and 19 with ARDS). In BALF, the average values of CI, CIII, PIIINP, and GGT were significantly higher in ARDS than in the control patients. The values for patients with pneumonia, although increased, were significantly lower than those in ARDS for CI, CIII, and PIIINP. In serum, the mean CI and PIIINP were significantly increased in pneumonia and ARDS, but the mean CIII was significantly increased only in ARDS compared with the control group. Significant positive linear correlations were observed for ARDS between CI and CIII or PIIINP and CIII in BALF and serum. Such correlations were observed for pneumonia only in serum. Molecular mass determinations demonstrated that CI- and CIII-related antigens in BALF were essentially intact triple helices of collagens or procollagens. Among patients with histologically defined interstitial fibrosis, the level of PIIINP in BALF was significantly higher for those with an additional intraalveolar fibrosis. In conclusion, measurements of these collagen markers may be useful for assessing disease activity and reflecting the flux of collagen molecules in the lung.

Ethylene glycol poisoning is a medical emergency. Making a definitive diagnosis is challenging because few institutions have timely access to direct measurement of ethylene glycol. After ingestion, primary metabolism of ethylene glycol takes place in the liver, leading to glycolic acid and glyoxylic acid. These compounds may cross-react with L-lactate oxidase used in blood gas analyzers lactate electrodes to induce false elevation of blood lactate. We present the case of a 47-year-old male patient initially admitted to the intensive care unit for severe lactate acidosis of unknown cause (pH 6.96, lactate, 30 mmol/L). Knowledge of potent artifactual lactate results was the key to the diagnosis of ethylene glycol poisoning, and false lactate measurements were found at the central laboratory on our 3 different blood gas analyzers.

Lactic acidosis previously has been reported during treatment of asthma with beta-2 agonists. However, this metabolic disturbance never had any clinical consequence. We report a case of a patient with asthma in whom beta-2 agonist administration increased dyspnea by metabolic acidosis due to a sharp increase in lactate levels (hyperlactatemia) and led to inappropriate intensification of bronchodilator therapy.

To the Editor: Experimental studies suggest that metabolic acidosis impairs the contractile function of the heart, but whether this occurs in humans is uncertain.1,2 During a six-month period, we m...

Objective. —To examine the incidence, risk factors, and outcome of severe sepsis in intensive care unit (ICU) patients. Design and Setting. —Inception cohort study from a 2-month prospective survey of 11 828 consecutive admissions to 170 adult ICUs of public hospitals in France. Patients. —Patients meeting clinical criteria for severe sepsis were included and classified as having documented infection (ie, documented severe sepsis, n=742), or a clinical diagnosis of infection without microbiological documentation (ie, culture-negative severe sepsis, n=310). Main Outcome Measures. —Hospital and 28-day mortality after severe sepsis. Results. —Clinically suspected sepsis and confirmed severe sepsis occurred in 9.0 (95% confidence interval [CI], 8.5 to 9.5) and 6.3 (95% CI, 5.8 to 6.7) of 100 ICU admissions, respectively. The 28-day mortality was 56% (95% CI, 52% to 60%) in patients with severe sepsis, and 60% (95% CI, 55% to 66%) in those with culture-negative severe sepsis. Major determinants of both early ( P P =.03), whereas secondary deaths were associated with the admission category ( P P P =.01) or cardiovascular ( P =.002) insufficiency, hypothermia ( P =.02), thrombocytopenia ( P =.01), and multiple sources of infection ( P =.02). In patients with documented sepsis, bacteremia was associated with early mortality ( P =.03). Conclusions. —Only three of four patients presenting with clinically suspected severe sepsis have documented infection. However, patients with clinically suspected sepsis but without microbiological documentation and patients with documented infection share common risk factors and are at similarly high risk of death. In addition to the severity of illness score, acute organ failures and the characteristics of underlying diseases should be accounted for in stratification of patients and outcome analyses. ( JAMA . 1995;274:968-974)