Cerebral autoregulation is influenced by carbon dioxide levels in patients with septic shock.

BACKGROUND: Altered brain perfusion may play an important role in the development of sepsis-associated encephalopathy. However, whether or not cerebral autoregulation (CA) is preserved in such condition has been debated. CA is dependent on cerebral vascular tone, the main determinant of which is the concentration of carbon dioxide (CO2). The purpose of this study was to evaluate the influence of PaCO2 on the cerebral autoregulatory capacity in patients with septic shock. METHODS: Using transcranial Doppler sonography recordings from the middle cerebral artery (MCA), we evaluated the static cerebral autoregulatory responses within the first 3 days of septic shock. Changes in cerebrovascular resistance (CVR) were calculated from the changes in the mean velocity in the MCA (VMCA, cm/s), in response to an increase in mean arterial pressure (MAP, mmHg) induced by vasopressors. The cerebral autoregulation index (CAI) was calculated as the ratio of the relative changes in CVR and MAP (CAI = DeltaMAP%/DeltaCVR%), with normal values ranging between 0 and 2. RESULTS: We studied 21 mechanically ventilated patients, with a baseline MAP of 65 +/- 6 mmHg, a mean VMCA of 60 +/- 20 cm/s and a median PaCO(2) of 35 [28-49] mmHg. Fourteen of the 21 patients had impaired CA, including 7 of the 14 patients with a PaCO2 <40 mmHg and all 7 patients with a PaCO2 >40 mmHg (Fisher's exact test, P = 0.046). CONCLUSIONS: According to these data, CA is impaired in the majority of patients with septic shock, especially in the presence of hypercapnia.

Quantitative TaqMan PCR for detection of Pneumocystis jiroveci.

We developed a quantitative real-time PCR assay for detection and quantification of Pneumocystis jiroveci in bronchoalveolar lavage (BAL) specimens based on primers and probe targeting the gene encoding beta-tubulin. The assay was able to detect 50 DNA copies per ml of a standard plasmid containing the target sequence. The intra- and interassay coefficients of variation were 0.46%-4.27% and 0.05-2.00% over 5 log(10) values. Fifty-seven controls of human, viruses, bacteria and fungi DNA samples were amplified and found negative. Fifty-three BAL samples sent to the laboratory for diagnosis of pneumocystosis were prospectively investigated by real-time PCR and direct microscopic examinations (DME) using Giemsa stain and direct immunofluorescence. All PCR negative samples were negative by microscopy. Among the 24 (45%) BAL found PCR positive, 8 were positive by microscopy (35%). The copy numbers of the target gene were between 4.4 x 10(3) and 2.8 x 10(6) per ml for the microscopically positive samples and between 8 and 9.2 x 10(3) per ml for the microscopically negative samples. In conclusion, we developed a rapid, sensitive and specific real time PCR for the diagnosis and quantification of Pneumocystis jiroveci in BAL samples.

Body temperature alterations in the critically ill.

OBJECTIVE: To determine the incidence of body temperature (BT) alterations in critically ill patients, and their relationship with infection and outcome. DESIGN: Prospective, observational study. SETTING. Thirty-one bed, medico-surgical department of intensive care. PATIENTS: Adult patients admitted consecutively to the ICU for at least 24 h, during 6 summer months. INTERVENTIONS: None. RESULTS: Fever (BT > or =38.3 degrees C) occurred in 139 (28.2%) patients and hypothermia (BT< or =36 degrees C) in 45 (9.1%) patients, at some time during the ICU stay. Fever was present in 52 of 100 (52.0%) infected patients without septic shock, and in 24 of 38 (63.2%) patients with septic shock. Hypothermia occurred in 5 of 100 (5.0%) infected patients without septic shock and in 5 of 38 (13.1%) patients with septic shock. Patients with hypothermia and fever had higher Sequential Organ Failure Assessment (SOFA) scores on admission (6.3+/-3.7 and 6.4+/-3.3 vs 4.6+/-3.2; p<0.01), maximum SOFA scores during ICU stay (7.6+/-5.2 and 8.2+/-4.7 vs 5.4+/-3.8; p<0.01) and mortality rates (33.3 and 35.3% vs 10.3%; p<0.01). The length of stay (LOS) was longer in febrile patients than in hypothermic and normothermic (36 degrees C

Infection Probability Score (IPS): A method to help assess the probability of infection in critically ill patients.

OBJECTIVE: To develop a simple score to help assess the presence or absence of infection in critically ill patients using routinely available variables. DESIGN: Observational study of a prospective cohort of patients divided into a developmental set (n = 353) and a validation set (n = 140). SETTING: Department of intensive care at an academic tertiary care center. PATIENTS: Four hundred and ninety-three adult patients admitted to the intensive care unit for > or =24 hrs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The presence of infection was defined using the Centers for Disease Control definitions. Body temperature, heart rate, respiratory rate, white blood cell count, and C-reactive protein concentrations were measured, and the Sequential Organ Failure Assessment score was calculated throughout the intensive care unit stay. Infection was documented in 92 of the 353 patients (26%) in the developmental set and in 41 of the 140 patients (29%) in the validation set. Univariate logistic regression was used to select significant predictors for infection. Each continuous predictor was transformed in a categorical variable using a robust locally weighted least square regression between infection and the continuous variable of interest. When more than two categories were created, the variable was separated into iso-weighted dummy variables. A multiple logistic regression model predicting infection was calculated with all the variables coded 1 or 0 allowing for relative scoring of the different predictors. The resulting Infection Probability Score consisted of six different variables and ranged from 0 to 26 points (0-2 for temperature, 0-12 for heart rate, 0-1 for respiratory rate, 0-3 for white blood cell count, 0-6 for C-reactive protein, 0-2 for Sequential Organ Failure Assessment score). The best predictors for infection were heart rate and C-reactive protein, whereas respiratory rate was found to have the poorest predictive value. The cutoff value for the Infection Probability Score was 14 points, with a positive predictive value of 53.6% and a negative predictive value of 89.5%. Model performance was very good (Hosmer-Lemeshow statistic, p =.918), and the areas under receiver operating characteristic curves were 0.820 for the developmental set and 0.873 for the validation set. CONCLUSIONS: The Infection Probability Score is a simple score that can help assess the probability of infection in critically ill patients. The variables used are simple, routinely available, and familiar to clinicians. Patients with a score <14 points have only a 10% risk of infection.

Gut mucosal and plasma concentrations of glutamine: a comparison between two enriched enteral feeding solutions in critically ill patients.

BACKGROUND: Addition of glutamine to enteral nutrition formulas is consistently associated with a significant decrease in septic morbidity in critically ill patients, possibly related to the attenuation of gut dysfunction. This pilot study was undertaken to compare the effects of enteral administration of two glutamine-enriched formulas containing either additional free glutamine or glutamine-rich proteins, with a standard solution on plasma and mucosal concentrations of glutamine in patients admitted in the Department of Intensive Care. METHODS: Following randomization, glutamine concentration was determined in endoscopically sampled duodenal biopsies and plasma, before and after a 7-day period of continuous administration of the designated solution. RESULTS: The mucosal concentration of glutamine increased in the duodenal biopsies sampled from patients randomized to the solution containing the glutamine-rich proteins (from 3.6 +/- 2.2 to 6.7 +/- 5.2 micro-mol/g protein), but not from the others. There were no differences between the 3 groups in the plasma concentrations of glutamine, which remained stable over time. CONCLUSION: The source of supplemental glutamine can influence gut mucosal glutamine concentrations, suggesting differences in its availability or utilization.

Are infections due to resistant pathogens associated with a worse outcome in critically ill patients?

OBJECTIVES: To evaluate the outcome of critically ill patients infected with antimicrobial resistant microorganisms, and to analyse the factors involved in the development of antimicrobial resistance. METHODS: All patients admitted to a 31-bed mixed medico-surgical intensive care unit who developed a nosocomial infection were prospectively followed until discharge or death. RESULTS: Of 949 consecutive patients admitted, 186 developed a nosocomial infection: 79 with an antimicrobial-resistant pathogen and 107 with susceptible strains. The lungs were the main source of infections in both groups. The main resistant microorganisms were Enterobacter aerogenes, methicillin resistant Staphylococcus aureus (MRSA), and Enterobacter cloacae. The main susceptible microorganisms were Enterobacter spp., methicillin susceptible S. aureus (MSSA), and Proteus mirabilis. Patients infected with resistant strains had a longer length of stay prior to infection (9+/-4 vs. 5+/-3 days), longer total length of stay (18+/-16 vs. 11+/-7 days), longer duration of mechanical ventilation (12+/-15 vs. 6+/-7 days), and more severe coagulation, liver, and renal dysfunction (all p<0.05). The maximum degrees of organ failure during the ICU stay, and the respiratory dysfunction, but not infection with a resistant pathogen, were independent predictors for death. Multivariate logistic regression revealed previous use of multiple antibiotics, duration of length of stay prior to infection, and the degree of liver failure as independent factors for development of infection with resistant organisms. CONCLUSIONS: Infection with antimicrobial resistant microorganisms is not an independent predictor for death. The development of antimicrobial resistance is related to the previous use of multiple antibiotics, the ICU length of stay, and the severity of hepatic dysfunction.

Long-term outcome in ICU patients: what about quality of life?

OBJECTIVE: Analysis of mortality and quality of life (QOL) after intensive care unit (ICU) discharge. DESIGN: Prospective, observational study. SETTING: Mixed, 31-bed, medico-surgical ICU. PATIENTS: Consecutive adult ICU admissions between June 25 and September 10, 2000, except admissions for uncomplicated elective postoperative surveillance. INTERVENTIONS. None. MEASUREMENTS AND RESULTS: Age, past history, admission APACHE II, SOFA score (admission, maximum, discharge), ICU and hospital mortality were recorded. A telephone interview employing the EuroQol 5D system was conducted 18 months after discharge. Of 202 patients, 34 (16.8%) died in the ICU and 23 (11.4%) died in the hospital after ICU discharge. Of the 145 patients discharged alive from hospital, 22 could not be contacted and 27 (13.4%) had died after hospital discharge. Of the 96 patients (47.5%) who completed the questionnaire, 38% had a worse QOL than prior to ICU admission, but only 8.3% were severely incapacitated. Twenty-three patients (24%) had reduced mobility, 15 (15.6%) had limited autonomy, 24 (25%) had alteration in usual daily activities, 29 (30.2%) expressed more anxiety/depression, and 42 (44%) had more discomfort or pain. Twenty-eight (62.2% of those who worked previously) patients had returned to work 18 months after ICU discharge. CONCLUSIONS: Comparing QOL after discharge with that before admission, patients more frequently report worse QOL for the domains of pain/discomfort and anxiety/depression than for physical domains. Factors commonly associated with a change in QOL were previous problems in the affected domains, prolonged hospital length of stay (LOS), greater disease severity at admission and degree of organ dysfunction during ICU stay.

The Multiple Organ Dysfunction Score (MODS) versus the Sequential Organ Failure Assessment (SOFA) score in outcome prediction.

OBJECTIVE: To compare outcome prediction using the Multiple Organ Dysfunction Score (MODS) and the Sequential Organ Failure Assessment (SOFA), two of the systems most commonly used to evaluate organ dysfunction in the intensive care unit (ICU). DESIGN: Prospective, observational study. SETTING: Thirty-one-bed, university hospital ICU. PATIENTS AND PARTICIPANTS: Nine hundred forty-nine ICU patients. MEASUREMENTS AND RESULTS: The MODS and the SOFA score were calculated on admission and every 48 h until ICU discharge. The Acute Physiology and Chronic Health Evaluation (APACHE) II score was calculated on admission. Areas under receiver operating characteristic (AUROC) curves were used to compare initial, 48 h, 96 h, maximum and final scores. Of the 949 patients, 277 died (mortality rate 29.1%). Shock was observed in 329 patients (mortality rate 55.3%). There were no significant differences between the two scores in terms of mortality prediction. Outcome prediction of the APACHE II score was similar to the initial MODS and SOFA score in all patients, and slightly worse in patients with shock. Using the scores' cardiovascular components (CV), outcome prediction was better for the SOFA score at all time intervals (initial AUROC SOFA CV 0.750 vs MODS CV 0.694, p<0.01; 48 h AUROC SOFA CV 0.732 vs MODS CV 0.675, p<0.01; and final AUROC SOFA CV 0.781 vs MODS CV 0.674, p<0.01). The same tendency was observed in patients with shock. There were no significant differences in outcome prediction for the other five organ systems. CONCLUSIONS: MODS and SOFA are reliable outcome predictors. Cardiovascular dysfunction is better related to outcome with the SOFA score than with the MODS.

Anemia and blood transfusion in critically ill patients.

CONTEXT: Anemia is a common problem in critically ill patients admitted to intensive care units (ICUs), but the consequences of anemia on morbidity and mortality in the critically ill is poorly defined. OBJECTIVES: To prospectively define the incidence of anemia and use of red blood cell (RBC) transfusions in critically ill patients and to explore the potential benefits and risks associated with transfusion in the ICU. DESIGN: Prospective observational study conducted November 1999, with 2 components: a blood sampling study and an anemia and blood transfusion study. SETTING AND PATIENTS: The blood sampling study included 1136 patients from 145 western European ICUs, and the anemia and blood transfusion study included 3534 patients from 146 western European ICUs. Patients were followed up for 28 days or until hospital discharge, interinstitutional transfer, or death. MAIN OUTCOME MEASURES: Frequency of blood drawing and associated volume of blood drawn, collected over a 24-hour period; hemoglobin levels, transfusion rate, organ dysfunction (assessed using the Sequential Organ Failure Assessment score), and mortality, collected throughout a 2-week period. RESULTS: The mean (SD) volume per blood draw was 10.3 (6.6) mL, with an average total volume of 41.1 (39.7) mL during the 24-hour period. There was a positive correlation between organ dysfunction and the number of blood draws (r = 0.34; P<.001) and total volume drawn (r = 0.28; P<.001). The mean hemoglobin concentration at ICU admission was 11.3 (2.3) g/dL, with 29% (963/3295) having a concentration of less than 10 g/dL. The transfusion rate during the ICU period was 37.0% (1307/3534). Older patients and those with a longer ICU length of stay were more commonly transfused. Both ICU and overall mortality rates were significantly higher in patients who had vs had not received a transfusion (ICU rates: 18.5% vs 10.1%, respectively; chi(2) = 50.1; P<.001; overall rates: 29.0% vs 14.9%, respectively; chi(2) = 88.1; P<.001). For similar degrees of organ dysfunction, patients who had a transfusion had a higher mortality rate. For matched patients in the propensity analysis, the 28-day mortality was 22.7% among patients with transfusions and 17.1% among those without (P =.02); the Kaplan-Meier log-rank test confirmed this difference. CONCLUSIONS: This multicenter observational study reveals the common occurrence of anemia and the large use of blood transfusion in critically ill patients. Additionally, this epidemiologic study provides evidence of an association between transfusions and diminished organ function as well as between transfusions and mortality.