Multicenter International Cohort Validation of a Modified Sequential Organ Failure Assessment Score Using the Richmond Agitation-sedation Scale.

OBJECTIVE: In a multicenter, international cohort, we aimed to validate a modified Sequential Organ Failure Assessment (mSOFA) using the Richmond Agitation-Sedation Scale, hypothesized as comparable to the Glasgow Coma Scale (GCS)-based Sequential Organ Failure Assessment (SOFA). SUMMARY BACKGROUND DATA: The SOFA score, whose neurologic component is based on the GCS, can predict intensive care unit (ICU) mortality. But, GCS is often missing in lieu of other assessments, such as the also reliable and validated Richmond Agitation Sedation Scale (RASS). Single-center data suggested an RASS-based SOFA (mSOFA) predicted ICU mortality. METHODS: Our nested cohort within the prospective 2016 Fourth International Study of Mechanical Ventilation contains 4120 ventilated patients with daily RASS and GCS assessments (20,023 patient-days, 32 countries). We estimated GCS from RASS via a proportional odds model without adjustment. ICU mortality logistic regression models and c-statistics were constructed using SOFA (measured GCS) and mSOFA (measured RASS-estimated GCS), adjusted for age, sex, body-mass index, region (Europe, USA-Canada, Latin America, Africa, Asia, Australia-New Zealand), and postoperative status (medical/surgical). RESULTS: Cohort-wide, the mean SOFA=9.4+/-2.8 and mean mSOFA = 10.0+/-2.3, with ICU mortality = 31%. Mean SOFA and mSOFA similarly predicted ICU mortality (SOFA: AUC = 0.784, 95% CI = 0.769-0.799; mSOFA: AUC = 0.778, 95% CI = 0.763-0.793, P = 0.139). Across models, other predictors of mortality included higher age, female sex, medical patient, and African region (all P < 0.001). CONCLUSIONS: We present the first SOFA modification with RASS in a "real-world" international cohort. Estimating GCS from RASS preserves predictive validity of SOFA to predict ICU mortality. Alternative neurologic measurements like RASS can be viably integrated into severity of illness scoring systems like SOFA.

Impact of Hyperoncotic Albumin on Duration of Vasopressor Support in Septic Shock: A Propensity Score-Matched Analysis.

BACKGROUND: While albumin has not been shown to reduce mortality in sepsis and septic shock, a tertiary analysis of a large trial suggested that it may reduce the duration of vasopressor use in septic shock. OBJECTIVE: We sought to test if 25% albumin administration was associated with reduced cumulative vasopressor use in septic shock in a real-world setting. METHODS: This was a retrospective, propensity score-matched cohort study of septic shock in which patients receiving albumin were compared with a matched cohort of those not receiving albumin. The primary outcome was days alive and free of vasopressors. RESULTS: The matched cohort included 335 patients who received albumin and 335 who did not. The days alive and free of vasopressors were similar between the albumin and no albumin groups: 17.4 (0-24.8) versus 19.4 (0-25.3); P = 0.160. Similarly, in-hospital mortality was no different between groups (46.9% vs 44.8%; P = 0.587). Receipt of albumin was associated with fewer ventilator-free and intensive care unit (ICU)-free days: 0 (0-19) versus 11 (0-23), P = 0.007, and 0 (0-18) versus 10.6 (0-22.1), P = 0.002, respectively. CONCLUSION AND RELEVANCE: Albumin use in septic shock was not associated with additional days alive and free of vasopressors or in-hospital mortality. The finding of fewer ventilator- and ICU-free days may reflect selection of patients who were critically ill for longer periods of time before or after albumin administration. Additional study is needed to clarify the impact that timing may have on the effectiveness of albumin in septic shock.

International Analgesia, Sedation, and Delirium Practices: a prospective cohort study.

BACKGROUND: While understanding of critical illness and delirium continue to evolve, the impact on clinical practice is often unknown and delayed. Our purpose was to provide insight into practice changes by characterizing analgesia and sedation usage and occurrence of delirium in different years and international regions. METHODS: We performed a retrospective analysis of two multicenter, international, prospective cohort studies. Mechanically ventilated adults were followed for up to 28 days in 2010 and 2016. Proportion of days utilizing sedation, analgesia, and performance of a spontaneous awakening trial (SAT), and occurrence of delirium were described for each year and region and compared between years. RESULTS: A total of 14,281 patients from 6 international regions were analyzed. Proportion of days utilizing analgesia and sedation increased from 2010 to 2016 (p < 0.001 for each). Benzodiazepine use decreased in every region but remained the most common sedative in Africa, Asia, and Latin America. Performance of SATs increased overall, driven mostly by the US/Canada region (24 to 35% of days with sedation, p < 0.001). Any delirium during admission increased from 7 to 8% of patients overall and doubled in the US/Canada region (17 to 36%, p < 0.001). CONCLUSIONS: Analgesia and sedation practices varied widely across international regions and significantly changed over time. Opportunities for improvement in care include increasing delirium monitoring, performing SATs, and decreasing use of sedation, particularly benzodiazepines.

Insidious Harm of Medication Diluents as a Contributor to Cumulative Volume and Hyperchloremia: A Prospective, Open-Label, Sequential Period Pilot Study.

OBJECTIVES: Although the potential dangers of hyperchloremia from resuscitation fluids continue to emerge, no study to date has considered the contribution of medication diluents to cumulative volume and hyperchloremia. This study compares saline versus dextrose 5% in water as the primary medication diluent and the occurrence of hyperchloremia in critically ill patients. DESIGN: Prospective, open-label, sequential period pilot study. SETTING: Medical ICU of a large academic medical center. PATIENTS: Adult patients admitted to the medical ICU were eligible for inclusion. Patients who were admitted for less than 48 hours, less than 18 years old, pregnant, incarcerated, or who had brain injury were excluded. INTERVENTIONS: Saline as the primary medication diluent for 2 months followed by dextrose 5% in water as the primary medication diluent for 2 months. MEASUREMENTS AND MAIN RESULTS: A total of 426 patients were included, 216 in the saline group and 210 in the dextrose 5% in water group. Medication diluents accounted for 63% of the total IV volume over the observation period. In the saline group, 17.9% developed hyperchloremia compared with 10.5% in the dextrose 5% in water group (p = 0.037), which was statistically significant in multivariable analysis (odds ratio, 0.50; 95% CI, 0.26-0.94; p = 0.031). In the saline group, 34.2% developed acute kidney injury versus 24.5% in the dextrose 5% in water group (p = 0.035); however, this was not statistically significant when adjusting for baseline covariates. No other significant differences in dysnatremias, insulin requirements, glucose control, ICU length of stay, or ICU mortality were observed. CONCLUSIONS: This study identified that medication diluents contribute substantially to the total IV volume received by critically ill patients. Saline as the primary medication diluent compared with dextrose 5% in water is associated with hyperchloremia, a possible risk factor for acute kidney injury.

Speciation of Zn-aminopolycarboxylic complexes by electrospray ionization mass spectrometry and ion chromatography with inductively coupled plasma mass spectrometry.

The speciation of Zn-aminopolycarboxylic complexes was investigated using both electrospray ionization mass spectrometry (ESI-MS) and ion chromatography (IC) with inductively coupled plasma mass spectrometry (ICP-MS). The resulting ESI mass spectra indicated that [Zn(HEDTA)](1-), [Zn(NTA)](1-), [Zn(EDTA)](2-) and [Zn(DTPA)](3-) were all simultaneously detected in solution; [Zn(NTA)](1-) exhibited the weakest intensity of all these Zn-aminopolycarboxylic complexes. IC/ICP-MS was also successfully used to separate Zn complexes by anion-exchange chromatography using a mobile phase containing 30 mM (NH(4))(2)HPO(4) at pH 7.5 giving reasonable resolution within 15 min. A weak peak attributable to the poor stability [Zn(NTA)](1-) ion was also observed using IC/ICP-MS. With the exception of [Zn(NTA)](1-), detection limits ranging from 0.5 to 1.0 microg/L were obtained and the proposed method was used for the determination of Zn aminopolycarboxylic complexes in soil solution.

Intestinal stem cells protect their genome by selective segregation of template DNA strands.

The stem cells in the crypts of the small intestinal mucosa divide about a thousand times during the lifespan of a laboratory mouse, and yet they show little evidence of any decline in proliferative potential and rarely develop carcinogenic mutations, suggesting that their genome is extremely well protected. Protection against DNA-replication-induced errors can be achieved by the selective sorting of old (template) and new DNA strands with all template strands retained in the stem cell line. The template strands in the stem cells can be labelled during development or during tissue regeneration using tritiated thymidine ((3)HTdR). Labelling newly synthesised strands with a different marker (bromodeoxyuridine, BrdUrd) allows segregation of the two markers to be studied. Template strand label is retained ((3)HTdR), whereas label in the newly synthesised strands (BrdUrd) is lost following the second division of the stem cell. Random errors may occur in the template strands owing to environmental elements. These are protected against by the altruistic cell suicide (apoptosis) of the cells incurring such errors. A final level of protection for the tissue compensates for excessive deletion of stem cells via the apoptosis pathway. This is achieved by a hierarchical age structure in the stem cell compartment, with some cells being able to efficiently repair DNA damage and hence being more radioresistant. The presence of these protective mechanisms ensures that the small intestine rarely develops cancer and that stem cells can sustain the extensive cell proliferation needed during life.