Clinically-oriented therapies in sepsis: a review.

Our insight of the sepsis response has evolved to encompass not only the pro-inflammatory but also an anti-inflammatory reaction following infection. Clinical trials have been designed to target either bacterial products, endotoxin in particular, or mediators involved in the sepsis response, but until recently the majority of them have given unfavorable results. In this article, we provide a scope of clinical trials that have been done in immunomodulation during sepsis whether or not they provide positive results. We will also discuss some of the reasons why those studies have been disappointing. Current and future trials with a better assessment of inflammatory status of patients and better-defined outcomes such as organ dysfunction are now underway.

Delirium in an intensive care unit: a study of risk factors.

OBJECTIVES: (1) To establish risk factors for the development of delirium in an intensive care unit (ICU) and (2) to determine the effect of delirium on morbidity, mortality and length of stay. DESIGN: Prospective study. SETTING: Sixteen-bed medical/surgical ICU in a university hospital. PATIENTS: Two hundred and sixteen consecutive patients admitted to the ICU for more than 24 h during 5 months were included in the study. INTERVENTIONS: Medical history, selected laboratory values, drugs received and factors that may influence patient psychological and emotional well-being were noted. All patients were screened with a delirium scale. A psychiatrist confirmed the diagnosis of delirium. Major complications such as self-extubation and removal of catheters, as well as mortality and length of stay were recorded. RESULTS: Forty patients (19%) developed delirium; of these, one-third were not agitated. In the multivariate analysis hypertension, smoking history, abnormal bilirubin level, epidural use and morphine were statistically significantly associated with delirium. Traditional factors associated with the development of delirium on general ward patients were not significant in our study. Morbidity (self-extubation and removal of catheters), but not mortality, was clearly increased. CONCLUSION: Predictive risk factors for the development of delirium in studies outside the ICU may not be applicable to critically ill patients. Delirium is associated with increased morbidity. Awareness of patients at risk may lead to better recognition and earlier intervention.

Intensive Care Delirium Screening Checklist: evaluation of a new screening tool.

OBJECTIVE: Delirium in the intensive care unit is poorly defined. Clinical evaluation is difficult in the setting of unstable, often intubated patients. A screening tool may improve the detection of delirium. METHOD: We created a screening checklist of eight items based on DSM criteria and features of delirium: altered level of consciousness, inattention, disorientation, hallucination or delusion, psychomotor agitation or retardation, inappropriate mood or speech, sleep/wake cycle disturbance, and symptom fluctuation. During 3 months, all patients admitted to a busy medical/surgical intensive care unit were evaluated, and the scale score was compared to a psychiatric evaluation. RESULTS: In 93 patients studied, 15 developed delirium. Fourteen (93%) of them had a score of 4 points or more. This score was also present in 15 (19%) of patients without delirium, 14 of whom had a known psychiatric illness, dementia, a structural neurological abnormality or encephalopathy. A ROC analysis was used to determine the sensitivity and specificity of the screening tool. The area under the ROC curve is 0.9017. Predicted sensitivity is 99% and specificity is 64%. CONCLUSION: This study suggests that the Intensive Care Delirium Screening Checklist can easily be applied by a clinician or a nurse in a busy critical care setting to screen all patients even when communication is compromised. The tool can be utilized quickly and helps to identify delirious patients. Earlier diagnosis may lead to earlier intervention and better patient care.

Are multiple blood transfusions really a cause of acute respiratory distress syndrome?

BACKGROUND AND OBJECTIVES: Multiple blood transfusions are considered a common cause of acute respiratory distress syndrome (ARDS). We hypothesized that ARDS is more a consequence of ARDS risk factors (in particular circulatory shock) requiring transfusions than a result of the transfusions themselves. METHODS: This retrospective study included 103 patients admitted during a 10-month period to an 858-bed university hospital who received multiple transfusions (more than six units of packed red blood cells in 24 h). RESULTS: Ten patients developed ARDS; they were more commonly admitted with circulatory shock (36 (38.7%) vs. 8 (80%), P = 0.01), polytrauma (7 (7.5%) vs. 4 (40%), P = 0.01) or thoracic trauma (3 (3.2%) vs. 4 (40%), P = 0.01). The sequential organ-failure assessment (SOFA) score at admission was higher in patients who developed ARDS than in those who did not (9.0 +/- 3.1 vs. 5.6 +/- 3.4, P < 0.005). The total amount of transfusion in the first 24 h was 14.0 +/- 6.8 U in the ARDS patients and 10.6 +/- 7.3 U in the other patients (P = 0.17); the differences remained non-significant in the following days. During the first 24 h, patients who developed ARDS received more fresh frozen plasma than those who did not (21.8 +/- 10.6 U vs. 10.7 +/- 14.7 U, P = 0.02). Patients who developed ARDS had lower PaO2/FiO2 ratios (114 +/- 61 mmHg vs. 276 +/- 108 mmHg, P = 0.01), lower arterial pH (7.27 +/- 0.10 vs. 7.34 +/- 0.11, P = 0.06) and higher minute volume (10.6 +/- 2.8 L min(-1) vs. 7.9 +/- 1.8 L min(-1), P = 0.03) than patients without ARDS. Multivariable analysis retained thoracic trauma and hypoxaemia during the first 24 h (but not multiple transfusions) as independent risk factors for ARDS. CONCLUSIONS: In this retrospective study, the development of ARDS in massively transfused patients was less related to poly-transfusion than to other factors related to circulatory shock, polytrauma or thoracic trauma. Thoracic trauma and a low PaO2 during the first 24 h were identified as independent risk factors for ARDS.

Assessment of the microcirculatory flow in patients in the intensive care unit.

Various techniques have been used at bedside to assess the microcirculation of critically ill patients, including nailfold videomicroscopy, laser doppler techniques, and orthogonal polarization spectral imaging. Nailfold videomicroscopy was introduced first, but its value may be limited by the extreme sensitivity of nailfold microcirculation to external temperature or vasoconstrictive agents. Laser Doppler techniques can measure gastric or jejunal mucosal blood flow as well as skin and muscle blood flow, but do not take into account blood flow heterogeneity, a major parameter of microcirculation. The recent introduction of orthogonal polarization spectral imaging techniques allows direct visualization of microcirculation in critically ill patients, opening a new area for the investigation of the pathophysiologic processes involved in the hemodynamic alterations of shock states.

Quality of sexually transmitted disease treatments in the formal and informal sectors of Bangui, Central African Republic.

BACKGROUND: Interventions for upgrading sexually transmitted disease (STD) management in sub-Saharan Africa have focused on the public sector, and to a much lower extent on private medical practitioners and pharmacies. However, in most African cities there is a large informal sector that provides care to many patients with STD symptoms. GOAL: To compare the quality of treatments offered to patients with major STD syndromes in the public sector, pharmacies, and the informal sector of the same city. STUDY DESIGN: Healthcare providers in health centers, pharmacies, private laboratories, and market drug peddlers in Bangui, Central African Republic, were asked to complete a short form for every patient consulting them with genital complaints. The treatments they ordered were evaluated for their potential efficacy against the major etiologic agents of the syndrome for which the patient consulted. RESULTS: The majority of male patients with STDs preferred to seek care in pharmacies and in the informal sector. The STD treatments offered to patients with urethral discharge or genital ulcers in pharmacies and in the informal sector tended to focus on a single etiologic agent. The quality of STD treatments offered by drug peddlers and private laboratories was poor, apart from adequate coverage of syphilis in patients with genital ulcers and of candidiasis in women with vaginal discharge. For instance, 41% and 34% of patients with urethral discharge managed by drug peddlers and private laboratories did not receive a drug active against either Neisseria gonorrhoeae or Chlamydia trachomatis, whereas this proportion was 22% in pharmacies and 14% in health centers. For patients with genital ulcers, the proportion offered a drug active against Haemophilus ducreyi was 2% if seen by drug peddlers, 0% in laboratories, 10% in pharmacies, and 25% in health centers. For each syndrome and each category of provider, between one fourth and two thirds of patients had already received another ineffective treatment elsewhere. CONCLUSION: National STD and HIV control programs will have to improve STD management in pharmacies and in the informal sector if they are to have any impact on the dynamics of HIV infection in urban centers.

Aetiology of urethral discharge in Bangui, Central African Republic.

OBJECTIVES: To determine the aetiology of urethritis in Bangui, Central African Republic. METHODS: 410 men presenting with urethral discharge and 100 asymptomatic controls were enrolled. Urethral swabs were obtained and processed by gonococcal culture and polymerase chain reaction for the detection of Neisseria gonorrhoeae, Chlamydia trachomatis, Mycoplasma genitalium, Trichomonas vaginalis, and Ureaplasma urealyticum. RESULTS: In multivariate analyses, M genitalium and C trachomatis were significantly associated with urethral discharge when comparing cases of non-gonococcal urethritis (NGU) with controls. T vaginalis was also more common in cases than in controls, but this reached statistical significance only among cases in whom N gonorrhoeae was also detected. U urealyticum was not associated with urethritis. The gonococcus was found in 69% of cases of urethral discharge. M genitalium was the predominant pathogen in patients with NGU, being found in 42% (53/127) of such patients while C trachomatis was found in only 17% (22/127). T vaginalis was found in 18% (23/127) of patients with NGU, but also in 15% (43/283) of patients with gonococcal urethritis, and two thirds of patients with T vaginalis also had the gonococcus. Multiple infections were common. M genitalium caused a syndrome similar to chlamydial urethritis, with a less severe inflammation than in gonococcal infection. No behavioural or clinical characteristic could discriminate between the various aetiological agents. CONCLUSIONS: M genitalium is more prevalent than C trachomatis and is the most common cause of NGU in BANGUI: It causes a syndrome similar to chlamydial urethritis. T vaginalis is weakly associated with urethritis, and is often found along with other pathogens.