Year in review 2006: Critical Care – resource management

As health care resources become increasingly constrained, it is imperative that intensive care unit resources be optimized. In the years to come, a number of challenges to intensive care medicine will need to be addressed as society changes. Last year's Critical Care papers provided us with a number of interesting and highly accessed original papers dealing with health care resources. The information yielded by these studies can help us to deal with issues such as prognostication, early detection and treatment of delirium, prevention of medical errors and use of radiology resources in critically ill patients. Finally, several aspects of scientific research in critically ill patients were investigated, focusing on the possibility of obtaining informed consent and recall of having given informed consent

Treatment of hypophosphatemia in the intensive care unit: a review

Introduction: Currently no evidence-based guideline exists for the approach to hypophosphatemia in critically ill patients. Methods: We performed a narrative review of the medical literature to identify the incidence, symptoms, and treatment of hypophosphatemia in critically ill patients. Specifically, we searched for answers to the questions whether correction of hypophosphatemia is associated with improved outcome, and whether a certain treatment strategy is superior. Results: Incidence: hypophosphatemia is frequently encountered in the intensive care unit; and critically ill patients are at increased risk for developing hypophosphatemia due to the presence of multiple causal factors. Symptoms: hypophosphatemia may lead to a multitude of symptoms, including cardiac and respiratory failure. Treatment: hypophosphatemia is generally corrected when it is symptomatic or severe. However, although multiple studies confirm the efficacy and safety of intravenous phosphate administration, it remains uncertain when and how to correct hypophosphatemia. Outcome: in some studies, hypophosphatemia was associated with higher mortality; a paucity of randomized controlled evidence exists for whether correction of hypophosphatemia improves the outcome in critically ill patients. Conclusions: Additional studies addressing the current approach to hypophosphatemia in critically ill patients are required. Studies should focus on the association between hypophosphatemia and morbidity and/or mortality, as well as the effect of correction of this electrolyte disorde

The incidence of low venous oxygen saturation on admission to the intensive care unit: a multi-center observational study in The Netherlands

Background Low mixed or central venous saturation (S(c)vO(2)) can reveal global tissue hypoxia and therefore can predict poor prognosis in critically ill patients. Early goal directed therapy (EGDT), aiming at an ScvO(2) >= 70%, has been shown to be a valuable strategy in patients with sepsis or septic shock and is incorporated in the Surviving Sepsis Campaign guidelines. Methods In this prospective observational multi-center study, we determined central venous pressure (CVP), hematocrit, pH, lactate and ScvO(2) or SvO(2) in a heterogeneous group of critically ill patients early after admission to the intensive care units (ICUs) in three Dutch hospitals. Results Data of 340 acutely admitted critically ill patients were collected. The mean SvO(2) value was > 65% and the mean ScvO(2) value was > 70%. With mean CVP of 10.3 +/- 5.5 mmHg, lactate plasma levels of 3.6 +/- 3.6 and acute physiology, age and chronic health evaluation (APACHE II) scores of 21.5 +/- 8.3, the in-hospital mortality of the total heterogeneous population was 32.0%. A subgroup of septic patients (n = 125) showed a CVP of 9.8 +/- 5.4 mmHg, mean ScvO(2) values of 74.0 +/- 10.2%, where only 1% in this subgroup revealed a ScvO(2) value <50%, and lactate plasma levels of 2.7 +/- 2.2 mmol/l with APACHE II scores 20.9 +/- 7.3. Hospital mortality of this subgroup was 26%. Conclusion The incidence of low ScvO(2) values for acutely admitted critically ill patients is low in Dutch ICUs. This is especially true for patients with sepsis/septic shock

Purification and characterization of an alcohol dehydrogenase from 1,2-propanediol-grown Desulfovibriostrain HDv

The sulfate-reducing bacterium Desulfovibrio strain HDv (DSM 6830) grew faster on (S)- and on (R, S)-1,2-propanediol (µmax 0.053 h–1) than on (R)-propanediol (0.017 h–1) and ethanol (0.027 h–1). From (R, S)-1,2-propanediol-grown cells, an alcohol dehydrogenase was purified. The enzyme was oxygen-labile, NAD-dependent, and decameric; the subunit mol. mass was 48 kDa. The N-terminal amino acid sequence indicated similarity to alcohol dehydrogenases belonging to family III of NAD-dependent alcohol dehydrogenases, the first 21 N-terminal amino acids being identical to those of the Desulfovibrio gigas alcohol dehydrogenase. Best substrates were ethanol and propanol (Km of 0.48 and 0.33 mM, respectively). (R, S)-1,2-Propanediol was a relatively poor substrate for the enzyme, but activities in cell extracts were high enough to account for the growth rate. The enzyme showed a preference for (S)-1,2-propanediol over (R)-1,2-propanediol. Antibodies raised against the alcohol dehydrogenase of D. gigas showed cross-reactivity with the alcohol dehydrogenase of Desulfovibrio strain HDv and with cell extracts of six other ethanol-grown sulfate-reducing bacteria.

Mechanical ventilation with lower tidal volumes does not influence the prescription of opioids or sedatives

INTRODUCTION: We compared the effects of mechanical ventilation with a lower tidal volume (V(T)) strategy versus those of greater V(T) in patients with or without acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) on the use of opioids and sedatives. METHODS: This is a secondary analysis of a previously conducted before/after intervention study, which consisting of feedback and education on lung protective mechanical ventilation using lower V(T). We evaluated the effects of this intervention on medication prescriptions from days 0 to 28 after admission to our multidisciplinary intensive care unit. RESULTS: Medication prescriptions in 23 patients before and 38 patients after intervention were studied. Of these patients, 10 (44%) and 15 (40%) suffered from ALI/ARDS. The V(T) of ALI/ARDS patients declined from 9.7 ml/kg predicted body weight (PBW) before to 7.8 ml/kg PBW after the intervention (P = 0.007). For patients who did not have ALI/ARDS there was a trend toward a decline from 10.2 ml/kg PBW to 8.6 ml/kg PBW (P = 0.073). Arterial carbon dioxide tension was significantly greater after the intervention in ALI/ARDS patients. Neither the proportion of patients receiving opioids or sedatives, or prescriptions at individual time points differed between pre-intervention and post-intervention. Also, there were no statistically significant differences in doses of sedatives and opioids. Findings were no different between non-ALI/ARDS patients and ALI/ARDS patients. CONCLUSION: Concerns regarding sedation requirements with use of lower V(T) are unfounded and should not preclude its use in patients with ALI/ARD

Secondary somatic mutations restoring RAD51C and RAD51D associated with acquired resistance to the PARP inhibitor rucaparib in high-grade ovarian carcinoma

High-grade epithelial ovarian carcinomas (OC) containing mutated BRCA1 or BRCA2 (BRCA1/2) homologous recombination (HR) genes are sensitive to platinum-based chemotherapy and poly(ADP-ribose) polymerase inhibitors (PARPi), while restoration of HR function due to secondary mutations in BRCA1/2 has been recognized as an important resistance mechanism. We sequenced core HR pathway genes in 12 pairs of pre-treatment and post-progression tumor biopsy samples collected from patients in ARIEL2 Part 1, a phase 2 study of the PARPi rucaparib as treatment for platinum-sensitive, relapsed OC. In six of 12 pre-treatment biopsies, a truncation mutation in BRCA1, RAD51C or RAD51D was identified. In five of six paired post-progression biopsies, one or more secondary mutations restored the open reading frame. Four distinct secondary mutations and spatial heterogeneity were observed for RAD51C. In vitro complementation assays and a patient-derived xenograft (PDX), as well as predictive molecular modeling, confirmed that resistance to rucaparib was associated with secondary mutations

Probing ISM Structure in Trumpler 14 & Carina I Using The Stratospheric Terahertz Observatory 2

We present observations of the Trumpler 14/Carina I region carried out using the Stratospheric Terahertz Observatory 2 (STO2). The Trumpler 14/Carina I region is in the west part of the Carina Nebula Complex, which is one of the most extreme star-forming regions in the Milky Way. We observed Trumpler 14/Carina I in the 158 $\mu$m transition of [C\,{\sc ii}] with a spatial resolution of 48$''$ and a velocity resolution of 0.17 km s$^{-1}$. The observations cover a 0.25$^\circ$ by 0.28$^\circ$ area with central position {\it l} = 297.34$^\circ$, {\it b} = -0.60$^\circ$. The kinematics show that bright [C\,{\sc ii}] structures are spatially and spectrally correlated with the surfaces of CO clouds, tracing the photodissociation region and ionization front of each molecular cloud. Along 7 lines of sight that traverse Tr 14 into the dark ridge to the southwest, we find that the [C\,{\sc ii}] luminosity from the HII region is 3.7 times that from the PDR. In same los we find in the PDRs an average ratio of 1:4.1:5.6 for the mass in atomic gas:dark-CO gas: molecular gas traced by CO. Comparing multiple gas tracers including HI 21cm, [C\,{\sc ii}], CO, and radio recombination lines, we find that the HII regions of the Carina Nebula Complex are well-described as HII regions with one-side freely expanding towards us, consistent with the champagne model of ionized gas evolution. The dispersal of the GMC in this region is dominated by EUV photoevaporation; the dispersal timescale is 20-30 Myr.Comment: ApJ accepte

Statistical Characterization of the Chandra Source Catalog

The first release of the Chandra Source Catalog (CSC) contains ~95,000 X-ray sources in a total area of ~0.75% of the entire sky, using data from ~3,900 separate ACIS observations of a multitude of different types of X-ray sources. In order to maximize the scientific benefit of such a large, heterogeneous data-set, careful characterization of the statistical properties of the catalog, i.e., completeness, sensitivity, false source rate, and accuracy of source properties, is required. Characterization efforts of other, large Chandra catalogs, such as the ChaMP Point Source Catalog (Kim et al. 2007) or the 2 Mega-second Deep Field Surveys (Alexander et al. 2003), while informative, cannot serve this purpose, since the CSC analysis procedures are significantly different and the range of allowable data is much less restrictive. We describe here the characterization process for the CSC. This process includes both a comparison of real CSC results with those of other, deeper Chandra catalogs of the same targets and extensive simulations of blank-sky and point source populations.Comment: To be published in the Astrophysical Journal Supplement Series (Fig. 52 replaced with a version which astro-ph can convert to PDF without issues.