Factors associated with meropenem pharmacokinetic/pharmacodynamic target attainment in septic critically ill patients treated with extended intermittent infusion or continuous infusion.

OBJECTIVES: The use of extended intermittent infusion (EII) or continuous infusion (CI) of meropenem is recommended in intensive care unit (ICU) patients, but few data comparing these two options are available. This retrospective cohort study was conducted between 1 January 2019 and 31 March 2020 in a teaching hospital ICU. It aimed to determine the meropenem plasma concentrations achieved with CI and EII. METHODS: The study included septic patients treated with meropenem who had one or more meropenem plasma trough (Cmin) or steady-state concentration (Css) measurement(s), as appropriate. It then assessed the factors independently associated with attainment of the target concentration (Cmin or Css ≥ 10 mg/L) and the toxicity threshold (Cmin or Css ≥ 50 mg/L) using logistic regression models. RESULTS: Among the 70 patients analysed, the characteristics of those treated with EII (n = 33) and CI (n = 37) were balanced with the exception of estimates glomerular filtration rate (eGFR): median 30 mL/min/m2 (IQR 30, 84) vs. 79 mL/min/m2 (IQR 30, 124). Of the patients treated with EII, 21 (64%) achieved the target concentration, whereas 31 (97%) of those treated with CI achieved it (P < 0.001). Factors associated with target attainment were: CI (OR 16.28, 95% CI 2.05-407.5), daily dose ≥ 40 mg/kg (OR 12.23, 95% CI 1.76-197.0; P = 0.03) and eGFR (OR 0.98, 95% CI 0.97-0.99; P = 0.02). Attainment of toxicity threshold was associated with daily dose > 70 mg/kg (OR 35.5, 95% CI 5.61-410.3; P < 0.001). CONCLUSION: The results suggest the use of meropenem CI at 40-70 mg/kg/day, particularly in septic ICU patients with normal or augmented renal clearance.

Population Pharmacokinetics of Isavuconazole in Critical Care Patients with COVID-19-Associated Pulmonary Aspergillosis and Monte Carlo Simulations of High Off-Label Doses.

Isavuconazole is a triazole antifungal agent recently recommended as first-line therapy for invasive pulmonary aspergillosis. With the COVID-19 pandemic, cases of COVID-19-associated pulmonary aspergillosis (CAPA) have been described with a prevalence ranging from 5 to 30%. We developed and validated a population pharmacokinetic (PKpop) model of isavuconazole plasma concentrations in intensive care unit patients with CAPA. Nonlinear mixed-effect modeling Monolix software were used for PK analysis of 65 plasma trough concentrations from 18 patients. PK parameters were best estimated with a one-compartment model. The mean of ISA plasma concentrations was 1.87 [1.29-2.25] mg/L despite prolonged loading dose (72 h for one-third) and a mean maintenance dose of 300 mg per day. Pharmacokinetics (PK) modeling showed that renal replacement therapy (RRT) was significantly associated with under exposure, explaining a part of clearance variability. The Monte Carlo simulations suggested that the recommended dosing regimen did not achieve the trough target of 2 mg/L in a timely manner (72 h). This is the first isavuconazole PKpop model developed for CAPA critical care patients underlying the need of therapeutic drug monitoring, especially for patients under RRT.

Sodium flux during hemodialysis and hemodiafiltration treatment of acute kidney injury: Effects of dialysate and infusate sodium concentration at 140 and 145 mmol/L.

BACKGROUND: A higher sodium (Na) dialysate concentration is recommended during renal replacement therapy (RRT) of acute kidney injury (AKI) to improve intradialytic hemodynamic tolerance, but it may lead to Na loading to the patient. We aimed to evaluate Na flux according to Na dialysate and infusate concentrations at 140 and 145 mmol/L during hemodialysis (HD) and hemodiafiltration (HDF). METHODS: Fourteen AKI patients that underwent consecutive HD or HDF sessions with Na dialysate/infusate at 140 and 145 mmol/L were included. Per-dialytic flux of Na was estimated using mean sodium logarithmic concentration including diffusive and convective influx. We compared the flux of sodium between HD140 and 145, and between HDF140 and 145. RESULTS: Nine HD140, ten HDF140, nine HD145, and 11 HDF145 sessions were analyzed. A Na gradient from the dialysate/replacement fluid to the patient was observed with dialysate/infusate Na at 145 mmol/L in both HD and HDF (p = 0.01). The comparison of HD145 to HD140 showed that higher Na dialysate induced a diffusive Na gradient to the patient (163 mmol vs. -25 mmol, p = 0.004) and that of HDF145 to -140 (211 vs. 36 mmol, p = 0.03) as well. Intradialytic hemodynamic tolerance was similar across all RRT sessions. CONCLUSIONS: During both HD and HDF, a substantial Na loading occurred with a Na dialysate and infusate at 145 mmol/L. This Na loading is smaller in HDF with Na dialysate and infusate concentration at 140 mmol/L and inversed with HD140. Clinical and intradialytic hemodynamic tolerance was fair regardless of Na dialysate and infusate.

Monocyte human leukocyte antigen-DR but not ß-D-glucan may help early diagnosing invasive Candida infection in critically ill patients.

BACKGROUND: Precision medicine risk stratification is desperately needed to both avoid systemic antifungals treatment delay and over prescription in the critically ill with risk factors. The aim of the present study was to explore the combination of host immunoparalysis biomarker (monocyte human leukocyte antigen-DR expression (mHLA-DR)) and Candida sp wall biomarker ß-D-glucan in risk stratifying patients for secondary invasive Candida infection (IC). METHODS: Prospective observational study. Two intensive care units (ICU). All consecutive non-immunocompromised septic shock patients. Serial blood samples (n = 286) were collected at day 0, 2 and 7 and mHLA-DR and ß-D-glucan were then retrospectively assayed after discharge. Secondary invasive Candida sp infection occurrence was then followed at clinicians' discretion. RESULTS: Fifty patients were included, 42 (84%) had a Candida score equal or greater than 3 and 10 patients developed a secondary invasive Candida sp infection. ICU admission mHLA-DR expression and ß-D-glucan (BDG) failed to predict secondary invasive Candida sp infection. Time-dependent cause-specific hazard ratio of IC was 6.56 [1.24-34.61] for mHLA-DR < 5000 Ab/c and 5.25 [0.47-58.9] for BDG > 350 pg/mL. Predictive negative value of mHLA-DR > 5000 Ab/c and BDG > 350 pg/mL combination at day 7 was 81% [95% CI 70-92]. CONCLUSIONS: This study suggests that mHLA-DR may help predicting IC in high-risk patients with septic shock. The added value of BDG and other fungal tests should be regarded according to the host immune function markers.

Admission High-Sensitive Cardiac Troponin T Level Increase Is Independently Associated with Higher Mortality in Critically Ill Patients with COVID-19: A Multicenter Study.

BACKGROUND: In coronavirus disease 2019 (COVID-19) patients, increases in high-sensitive cardiac troponin T (hs-cTnT) have been reported to be associated with worse outcomes. In the critically ill, the prognostic value of hs-cTnT, however, remains to be assessed given that most previous studies have involved a case mix of non- and severely ill COVID-19 patients. METHODS: We conducted, from March to May 2020, in three French intensive care units (ICUs), a multicenter retrospective cohort study to assess in-hospital mortality predictability of hs-cTnT levels in COVID-19 patients. RESULTS: 111 laboratory-confirmed COVID-19 patients (68% of male, median age 67 (58-75) years old) were included. At ICU admission, the median Charlson Index, Simplified Acute Physiology Score II, and PaO2/FiO2 were at 3 (2-5), 37 (27-48), and 140 (98-154), respectively, and the median hs-cTnT serum levels were at 16.0 (10.1-31.9) ng/L. Seventy-five patients (68%) were mechanically ventilated, 41 (37%) were treated with norepinephrine, and 17 (15%) underwent renal replacement therapy. In-hospital mortality was 29% (32/111) and was independently associated with lower PaO2/FiO2 and higher hs-cTnT serum levels. CONCLUSIONS: At ICU admission, besides PaO2/FiO2, hs-cTnT levels may allow early risk stratification and triage in critically ill COVID-19 patients.

Impact of Videolaryngoscopy Expertise on First-Attempt Intubation Success in Critically Ill Patients.

OBJECTIVES: The use of a videolaryngoscope in the ICU on the first endotracheal intubation attempt and intubation-related complications is controversial. The objective of this study was to evaluate the first intubation attempt success rate in the ICU with the McGrath MAC videolaryngoscope (Medtronic, Minneapolis, MN) according to the operators' videolaryngoscope expertise and to describe its association with the occurrence of intubation-related complications. DESIGN: Observational study. SETTING: Medical ICU. SUBJECTS: Consecutive endotracheal intubations in critically ill patients. INTERVENTIONS: Systematic use of the videolaryngoscope. MEASUREMENTS AND MAIN OUTCOMES: We enrolled 202 consecutive endotracheal intubations. Overall first-attempt success rate was 126 of 202 (62%). Comorbidities, junior operator, cardiac arrest upon admission, and coma were associated with a lower first-attempt success rate. The first-attempt success rate was less than 50% in novice operators (1-5 previous experiences with videolaryngoscope, independently of airway expertise with direct laryngoscopies) and 87% in expert operators (> 15 previous experiences with videolaryngoscope). Multivariate analysis confirmed the association between specific skill training with videolaryngoscope and the first-attempt success rate. Severe hypoxemia and overall immediate intubation-related complications occurred more frequently in first-attempt failure intubations (24/76, 32%) than in first-attempt success intubations (14/126, 11%) (p < 0.001). CONCLUSIONS: We report for the first time in the critically ill that specific videolaryngoscopy skill training, assessed by the number of previous videolaryngoscopies performed, is an independent factor of first-attempt intubation success. Furthermore, we observed that specific skill training with the McGrath MAC videolaryngoscope was fast. Therefore, future trials evaluating videolaryngoscopy in ICUs should consider the specific skill training of operators in videolaryngoscopy.

Risk factors and outcomes for airway failure versus non-airway failure in the intensive care unit: a multicenter observational study of 1514 extubation procedures.

BACKGROUND: Patients liberated from invasive mechanical ventilation are at risk of extubation failure, including inability to breathe without a tracheal tube (airway failure) or without mechanical ventilation (non-airway failure). We sought to identify respective risk factors for airway failure and non-airway failure following extubation. METHODS: The primary endpoint of this prospective, observational, multicenter study in 26 intensive care units was extubation failure, defined as need for reintubation within 48 h following extubation. A multinomial logistic regression model was used to identify risk factors for airway failure and non-airway failure. RESULTS: Between 1 December 2013 and 1 May 2015, 1514 patients undergoing extubation were enrolled. The extubation-failure rate was 10.4% (157/1514), including 70/157 (45%) airway failures, 78/157 (50%) non-airway failures, and 9/157 (5%) mixed airway and non-airway failures. By multivariable analysis, risk factors for extubation failure were either common to airway failure and non-airway failure: intubation for coma (OR 4.979 (2.797-8.864), P < 0.0001 and OR 2.067 (1.217-3.510), P = 0.003, respectively, intubation for acute respiratory failure (OR 3.395 (1.877-6.138), P < 0.0001 and OR 2.067 (1.217-3.510), P = 0.007, respectively, absence of strong cough (OR 1.876 (1.047-3.362), P = 0.03 and OR 3.240 (1.786-5.879), P = 0.0001, respectively, or specific to each specific mechanism: female gender (OR 2.024 (1.187-3.450), P = 0.01), length of ventilation > 8 days (OR 1.956 (1.087-3.518), P = 0.025), copious secretions (OR 4.066 (2.268-7.292), P < 0.0001) were specific to airway failure, whereas non-obese status (OR 2.153 (1.052-4.408), P = 0.036) and sequential organ failure assessment (SOFA) score ≥ 8 (OR 1.848 (1.100-3.105), P = 0.02) were specific to non-airway failure. Both airway failure and non-airway failure were associated with ICU mortality (20% and 22%, respectively, as compared to 6% in patients with extubation success, P < 0.0001). CONCLUSIONS: Specific risk factors have been identified, allowing us to distinguish between risk of airway failure and non-airway failure. The two conditions will be managed differently, both for prevention and curative strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT 02450669 . Registered on 21 May 2015.

Correction to: Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

The members of the Palurea Study Group were provided in such a way that they could not be indexed as collaborators on PubMed. The publisher apologizes for this error and is pleased to list the members of the group here.

Mortality Associated with Night and Weekend Admissions to ICU with On-Site Intensivist Coverage: Results of a Nine-Year Cohort Study (2006-2014).

BACKGROUND: The association between mortality and time of admission to ICU has been extensively studied but remains controversial. We revaluate the impact of time of admission on ICU mortality by retrospectively investigating a recent (2006-2014) and large ICU cohort with on-site intensivist coverage. PATIENTS AND METHODS: All adults (≥ 18 years) admitted to a tertiary care medical ICU were included in the study. Patients' characteristics, medical management, and mortality were prospectively collected. Patients were classified according to their admission time: week working days on- and off-hours, and weekends. ICU mortality was the primary outcome and adjusted Hazard-ratios (HR) of death were analysed by multivariate Cox model. RESULTS: 2,428 patients were included: age 62±18 years; male: 1,515 (62%); and median SAPSII score: 38 (27-52). Overall ICU mortality rate was 13.7%. Admissions to ICU occurred during open-hours in 680 cases (28%), during night-time working days in 1,099 cases (45%) and during weekends in 649 cases (27%). Baseline characteristics of patients were similar between groups except that patients admitted during the second part of night (00:00 to 07:59) have a significantly higher SAPS II score than others. ICU mortality was comparable between patients admitted during different time periods but was significantly higher for those admitted during the second part of the night. Multivariate analysis showed however that admission during weeknights and weekends was not associated with an increased ICU mortality as compared with open-hours admissions. CONCLUSION: Time of admission, especially weeknight and weekend (off-hour admissions), did not influence the prognosis of ICU patients. The higher illness severity of patients admitted during the second part of the night (00:00-07:59) may explain the observed increased mortality.

Diagnostic and prognostic value of soluble CD14 subtype (Presepsin) for sepsis and community-acquired pneumonia in ICU patients.

BACKGROUND: The soluble CD14 subtype, Presepsin, appears to be an accurate sepsis diagnostic marker, but data from intensive care units (ICUs) are scarce. This study was conducted to evaluate the diagnostic and prognostic value of Presepsin in ICU patients with severe sepsis (SS), septic shock (SSh) and severe community-acquired pneumonia (sCAP). METHODS: Presepsin and procalcitonin (PCT) levels were determined for patients at admission to ICU. Four groups have been differentiated: (1) absence or (2) presence of systemic inflammatory response syndrome, (3) SS or (4) SSh; and 2 groups, among the patients admitted for acute respiratory failure: absence or presence of sCAP. Biomarkers were tested for diagnosis of SS, SSh and sCAP and for prediction of ICU mortality. RESULTS: One hundred and forty-four patients were included: 44 SS and 56 SSh. Plasma levels of Presepsin and PCT were significantly higher in septic than in non-septic patients and in SSh as compared to others. The sepsis diagnostic accuracy of Presepsin was not superior to that of PCT (AUC: 0.75 vs 0.80). In the 72/144 patients admitted for acute respiratory failure, the capability of Presepsin to diagnose sCAP was significantly better than PCT. Presepsin levels were also predictive of ICU mortality in sepsis and in sCAP patients. CONCLUSION: Plasma levels of Presepsin were useful for the diagnosis of SS, SSh and sCAP and may predict ICU mortality in these patients.

Imported falciparum malaria in adults: host- and parasite-related factors associated with severity. The French prospective multicenter PALUREA cohort study.

PURPOSE: Prospective data on potential factors associated with severity of imported Plasmodium falciparum malaria are lacking. We evaluated whether several host- and parasite-related biomarkers may improve early severity evaluation. METHODS: Prospective multicenter observational study comparing uncomplicated and severe imported falciparum malaria in adults conducted in France in 52 units, from 2007 to 2010. Association of several host- and parasite-related biomarkers with severity of malaria was tested using univariate and multivariate analyses. RESULTS: Of 295 patients, 140 had uncomplicated malaria and 155 severe malaria (including very severe and less severe cases according to predefined criteria). Curative intravenous quinine treatment was used in 154/155 patients with severe malaria and atovaquone/proguanil in 74 % of patients with uncomplicated malaria. Hospital mortality was 5.2 % (8 patients), all in the severe malaria group. Among host-related biomarkers, CRP, procalcitonin, and sTREM-1 were significantly higher and albumin was significantly lower in severe versus uncomplicated malaria; only the last three biomarkers also differed significantly between the very and less severe malaria groups. Among parasite-related biomarkers, only plasma PfHRP2 was significantly higher in severe versus uncomplicated malaria and in very severe versus less severe malaria; parasitemia did not differ between very and less severe malaria. By multivariate analysis, only lower plasma albumin and higher sTREM-1 were associated with greater severity, with intermediate accuracies. CONCLUSIONS: During imported malaria, the most useful biomarkers associated with severity seem to be plasma albumin and sTREM-1; and among parasite-related parameters, PfHRP2 was more strongly associated with severity than parasitemia was.

Nutrition rehabilitation in the intensive care unit.

The maintenance of homeostasis after severe injury requires the restoration of the physiological regulation of food intake. A wide array of functional alterations can hinder the intake of adequate amounts of nutrients to support the recovery from critical illness. These alterations encompass changes in the preprandial phase, reflected by a loss of appetite; changes in the prandial phase, yielding swallowing disorders; and changes in the postprandial phase, including impairments of gastric emptying, gut motility, and satiety. This tutorial aims to review these often overlooked features and to suggest recommendations for the nutrition rehabilitation of the critically ill.

Methicillin-sensitive Staphylococcus aureus CC398 in intensive care unit, France.

During testing for Staphylococcus aureus in an intensive care unit in France in 2011, we found that methicillin-sensitive S. aureus clonal complex 398 was the most frequent clone (29/125, 23.2%). It was isolated from patients (5/89, 5.6%), health care workers (2/63, 3.2%), and environmental sites (15/864, 1.7%). Results indicate emergence of this clone in a hospital setting.

Prognosis and ICU outcome of systemic vasculitis.

BACKGROUND: Systemic vasculitis may cause life threatening complications requiring admission to an intensive care unit (ICU). The aim of this study was to evaluate outcomes of systemic vasculitis patients admitted to the ICU and to identify prognosis factors. METHODS: During a ten-year period, records of 31 adult patients with systemic vasculitis admitted to ICUs (median age: 63 y.o, sex ratio M/F: 21/10, SAPS II: 40) were reviewed including clinical and biological parameters, use of mechanical ventilation, catecholamine or/and dialysis support. Mortality was assessed and data were analyzed to identify predictive factors of outcome. RESULTS: Causes of ICU admissions were active manifestation of vasculitis (n = 19), septic shock (n = 8) and miscellaneous (n = 4). Sixteen patients (52%) died in ICU. By univariate analysis, mortality was associated with higher SOFA (p = 0.006) and SAPS II (p = 0.004) scores. The need for a catecholamine support or/and a renal replacement therapy, and the occurrence of an ARDS significantly worsen the prognosis. By multivariate analysis, only SAPS II (Odd ratio: 1.16, 95% CI [1.01; 1.33]) and BVAS scores (Odd ratio: 1.16, 95% CI = [1.01; 1.34]) were predictive of mortality. CONCLUSION: The mortality rate of severe vasculitis requiring an admission to ICU was high. High levels of SAPS II and BVAS scores at admission were predictive of mortality.

DNAGear--a free software for spa type identification in Staphylococcus aureus.

BACKGROUND: Staphylococcus aureus is both human commensal and an important human pathogen, responsible for community-acquired and nosocomial infections ranging from superficial wound infections to invasive infections, such as osteomyelitis, bacteremia and endocarditis, pneumonia or toxin shock syndrome with a mortality rate up to 40%. S. aureus reveals a high genetic polymorphism and detecting the genotypes is extremely useful to manage and prevent possible outbreaks and to understand the route of infection. One of current and expanded typing method is based on the X region of the spa gene composed of a succession of repeats of 21 to 27 bp. More than 10000 types are known. Extracting the repeats is impossible by hand and needs a dedicated software. Unfortunately the only software on the market is a commercial program from Ridom. FINDINGS: This article presents DNAGear, a free and open source software with a user friendly interface written all in Java on top of NetBeans Platform to perform spa typing, detecting new repeats and new spa types and synchronizing automatically the files with the open access database. The installation is easy and the application is platform independent. In fact, the SPA identification is a formal regular expression matching problem and the results are 100% exact. As the program is using Java embedded modules written over string manipulation of well established algorithms, the exactitude of the solution is perfectly established. CONCLUSIONS: DNAGear is able to identify the types of the S. aureus sequences and detect both new types and repeats. Comparing to manual processing, which is time consuming and error prone, this application saves a lot of time and effort and gives very reliable results. Additionally, the users do not need to prepare the forward-reverse sequences manually, or even by using additional tools. They can simply create them in DNAGear and perform the typing task. In short, researchers who do not have commercial software will benefit a lot from this application.

Short- and long-term outcomes of HIV-infected patients admitted to the intensive care unit: impact of antiretroviral therapy and immunovirological status.

BACKGROUND: The purpose of this study was to assess the short- and long-term outcomes of HIV-infected patients admitted to intensive care units (ICU) according to immunovirological status at admission and highly active antiretroviral therapy (HAART) use in ICU. METHODS: Retrospective study of 98 HIV-infected patients hospitalized between 1997 and 2008 in two medical ICU in Montpellier, France. The primary outcome was mortality in ICU. The secondary end point was probability of survival in the year following ICU admission. RESULTS: Eighty-two (83.6%) admissions in ICU were related to HIV infection and 45% of patients had received HAART before admission. Sixty-two patients (63.3%) were discharged from ICU, and 34 (34.7%) were alive at 1 year. Plasma HIV RNA viral load (VL) and CD4+ cell count separately were not associated with outcome. Independent predictors of ICU mortality were the use of vasopressive agents (odds ratio (OR), 3.779; 95% confidence interval (CI), 1.11-12.861; p = 0.0334) and SAPS II score (OR, 1.04; 95% CI, 1.003-1.077; p = 0.0319), whereas introducing or continuing HAART in ICU was protective (OR, 0.278; 95% CI, 0.082-0.939; p = 0.0393). Factors independently associated with 1-year mortality were immunovirological status with high VL (>3 log10/ml) and low CD4 (<200/mm3; hazard ratio (HR), 5.19; 95% CI, 1.328-20.279; p = 0.0179) or low VL (<3 log10/ml) and low CD4 (HR, 4.714; 95% CI, 1.178-18.867; p = 0.0284) vs. high CD4 and low VL, coinfection with C hepatitis virus (HR, 3.268; 95% CI, 1.29-8.278; p = 0.0125), the use of vasopressive agents (HR, 3.68; 95% CI, 1.394-9.716; p = 0.0085), and SAPS II score (HR, 1.09; 95% CI, 1.057-1.124; p <0.0001). Introducing HAART in a patient with no HAART at admission was associated with a better long-term outcome (HR, 0.166; 95% CI, 0.043-0.642; p = 0.0093). CONCLUSIONS: In a population of HIV-infected patients admitted to ICU, short- and long-term outcomes are related to acute illness severity and immunovirological status at admission. Complementary studies are necessary to identify HIV-infected patients who benefit from HAART use in ICU according to immunovirological status and the reasons of ICU admission.

Clinical review of eight patients with acute respiratory distress syndrome due to pulmonary tuberculosis.

Pulmonary tuberculosis can lead to acute respiratory distress syndrome (ARDS) even in the absence of superinfection, and this condition requires mechanical ventilation. We describe herein the characteristics and outcomes of 8 patients with this association hospitalized in a French teaching hospital between 1997 and 2006.

Severe metabolic or mixed acidemia on intensive care unit admission: incidence, prognosis and administration of buffer therapy. A prospective, multiple-center study.

INTRODUCTION: In this study, we sought describe the incidence and outcomes of severe metabolic or mixed acidemia in critically ill patients as well as the use of sodium bicarbonate therapy to treat these illnesses. METHODS: We conducted a prospective, observational, multiple-center study. Consecutive patients who presented with severe acidemia, defined herein as plasma pH below 7.20, were screened. The incidence, sodium bicarbonate prescription and outcomes of either metabolic or mixed severe acidemia were analyzed. RESULTS: Among 2, 550 critically ill patients, 200 (8%) presented with severe acidemia, and 155 (6% of the total admissions) met the inclusion criteria. Almost all patients needed mechanical ventilation and vasopressors during their ICU stay, and 20% of them required renal replacement therapy within the first 24 hours of their ICU stay. Severe metabolic or mixed acidemia was associated with a mortality rate of 57% in the ICU. Delay of acidemia recovery as opposed to initial pH value was associated with increased mortality in the ICU. The type of acidemia did not influence the decision to administer sodium bicarbonate. CONCLUSIONS: The incidence of severe metabolic or mixed acidemia in critically ill patients was 6% in the present study, and it was associated with a 57% mortality rate in the ICU. In contradistinction with the initial acid-base parameters, the rapidity of acidemia recovery was an independent risk factor for mortality. Sodium bicarbonate prescription was very heterogeneous between ICUs. Further studies assessing specific treatments may be of interest in this population.

Severe imported falciparum malaria: a cohort study in 400 critically ill adults.

BACKGROUND: Large studies on severe imported malaria in non-endemic industrialized countries are lacking. We sought to describe the clinical spectrum of severe imported malaria in French adults and to identify risk factors for mortality at admission to the intensive care unit. METHODOLOGY AND PRINCIPAL FINDINGS: Retrospective review of severe Plasmodium falciparum malaria episodes according to the 2000 World Health Organization definition and requiring admission to the intensive care unit. Data were collected from medical charts using standardised case-report forms, in 45 French intensive care units in 2000-2006. Risk factors for in-hospital mortality were identified by univariate and multivariate analyses. Data from 400 adults admitted to the intensive care unit were analysed, representing the largest series of severe imported malaria to date. Median age was 45 years; 60% of patients were white, 96% acquired the disease in sub-Saharan Africa, and 65% had not taken antimalarial chemoprophylaxis. Curative quinine treatment was used in 97% of patients. Intensive care unit mortality was 10.5% (42 deaths). By multivariate analysis, three variables at intensive care unit admission were independently associated with hospital death: older age (per 10-year increment, odds ratio [OR], 1.72; 95% confidence interval [95%CI], 1.28-2.32; P = 0.0004), Glasgow Coma Scale score (per 1-point decrease, OR, 1.32; 95%CI, 1.20-1.45; P<0.0001), and higher parasitemia (per 5% increment, OR, 1.41; 95%CI, 1.22-1.62; P<0.0001). CONCLUSIONS AND SIGNIFICANCE: In a large population of adults treated in a non-endemic industrialized country, severe malaria still carried a high mortality rate. Our data, including predictors of death, can probably be generalized to other non-endemic countries where high-quality healthcare is available.

An intervention to decrease complications related to endotracheal intubation in the intensive care unit: a prospective, multiple-center study.

OBJECTIVE: To determined whether the implementation of an intubation management protocol leads to the reduction of intubation-related complications in the intensive care unit (ICU). DESIGN: Two-phase, prospective, multicenter controlled study. SETTING: Three medical-surgical ICUs in two university hospitals. PATIENTS: Two hundred three consecutive ICU patients required 244 intubations. INTERVENTIONS: All intubations performed during two consecutive phases (a 6-month quality control phase followed by a 6-month intervention phase based on the implementation of an ICU intubation bundle management protocol) were evaluated. The ten bundle components were: preoxygenation with noninvasive positive pressure ventilation, presence of two operators, rapid sequence induction, cricoid pressure, capnography, protective ventilation, fluid loading, preparation and early administration of sedation and vasopressor use if needed. MEASUREMENTS AND MAIN RESULTS: The primary end points were the incidence of life-threatening complications occurring within 60 min after intubation (cardiac arrest or death, severe cardiovascular collapse and hypoxemia). Other complications (mild to moderate) were also evaluated. Baseline characteristics, including demographic data and reason for intubation (mainly acute respiratory failure), were similar in the two phases. The intubation procedure in the intervention phase (n = 121) was associated with significant decreases in both life-threatening complications (21 vs. 34%, p = 0.03) and other complications (9 vs. 21%, p = 0.01) compared to the control phase (n = 123). CONCLUSIONS: The implementation of an intubation management protocol can reduce immediate severe life-threatening complications associated with intubation of ICU patients.