2010 Annual Evidence Update on Critical Illness Rehabilitation

For this annual evidence update a detailed literature review was undertaken to retrieve any evidence published subsequent to the literature search which formed the basis for the NICE guideline. A total of 29 articles were selected for review and appraisal by a team of critical care practitioners. In this context it has to be noted that the evidence base on the subject is still relatively small. For the original guideline only 12 articles were selected as evidence which addressed the review questions. This evidence update intends to give an indication of encouraging trends within critical illness rehabilitation

Combined visible and near-infrared OPA for wavelength scaling experiments in strong-field physics

We report the operation of an optical parametric amplifier (OPA) capable of producing gigawatt peak-power laser pulses with tunable wavelength in either the visible or near-infrared spectrum. The OPA has two distinct operation modes (i) generation of >350 uJ, sub 100 fs pulses, tunable between 1250 - 1550 nm; (ii) generation of >190 uJ, sub 150 fs pulses tunable between 490 - 530 nm. We have recorded high-order harmonic spectra over a wide range of driving wavelengths. This flexible source of femtosecond pulses presents a useful tool for exploring the wavelength-dependence of strong-field phenomena, in both the multi-photon and tunnel ionization regimes.Comment: 14 pages, 9 figures, This paper was published in Proceedings of SPIE 10088, Nonlinear Frequency Generation and Conversion: Materials and Devices XVI, doi 10.1117/12.225077

Management of sodium disorders during continuous haemofiltration

In patients with acute kidney injury and concomitant severe hyponatraemia or hypernatraemia, rapid correction of the serum Na+ concentration needs to be avoided. The present paper outlines the principles of how to adjust the Na+ concentration in the replacement fluid during continuous renal replacement therapy to prevent rapid changes of the serum Na+ concentration

Rapid nano-gram scale screening method of micro-arrays to evaluate drug-polymer blends using high-throughput printing technology

A miniaturized, high-throughput assay was optimized to screen polymer-drug solid dispersions using a 2-D Ink-jet printer. By simply printing nanoliter amounts of polymer and drug solutions onto an inert surface, drug:polymer micro-dots of tunable composition were produced in an easily-addressable micro-array format. The amount of material printed for each dried spot ranged from 25 ng to 650 ng. These arrays were used to assess the stability of drug:polymer dispersions with respect to recrystallization, using polarized light microscopy. One array with a panel of 6 drugs formulated at different ratios with Poly (vinylpyrrolidone-vinyl acetate) copolymer (PVPVA) was developed to estimate a possible bulk (gram-scale) approximation threshold from the final printed nano amount of formulation. Another array was printed at a fixed final amount of material to establish a literature comparison of one drug formulated with different commercial polymers for validation. This new approach may offer significant efficiency in pharmaceutical formulation screening, with each experiment in the nano-micro-array format requiring from 3 up to 6 orders of magnitude lower amounts of sample than conventional screening methods

Cardiac biomarkers are associated with maximum stage of acute kidney injury in critically ill patients:A prospective analysis

Background: This study aimed to investigate whether cardiac troponin T (cTnT), cardiac troponin I (cTnI) and serum N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with acute kidney injury (AKI) and need for acute renal replacement therapy (RRT) in adult patients admitted to the intensive care unit (ICU). Methods: We analysed prospectively collected data for patients admitted to the ICU between June and December 2010 for non-cardiac reasons. The Kidney Disease Improving Global Outcomes creatinine criteria were applied to identify patients with AKI including those who received acute RRT. Severity of illness was determined by the Acute Physiology and Chronic Health Evaluation (APACHE) II score and the Serial Organ Failure Assessment (SOFA) score. Regression analyses were performed to assess the association between cTnT, cTnI and NT-proBNP concentrations on the first day of ICU stay, maximum AKI stages and need for acute RRT. Sensitivity analysis was performed in which patients who developed a myocardial infarction during their stay in the ICU were excluded. Results: Of 138 patients included, 73 (53%) had AKI and 40 (29%) required acute RRT. Patients with AKI were significantly older, more likely to have sepsis and had higher APACHE II and SOFA scores on admission to the ICU. In univariable analysis, cTnT, cTnI and NT-proBNP were significantly higher in those with AKI requiring acute RRT, but after adjustment for baseline differences in severity of illness, cumulative fluid balance and pre-existing comorbidities, only NT-proBNP remained significantly associated with worst stage of AKI and need for RRT. cTnT and cTnI were independently associated with the odds of any AKI but not with need for RRT. In a sensitivity analysis in which patients who had an acute myocardial infarction while in the ICU were excluded, NT-proBNP remained independently associated with AKI and acute RRT. Conclusions: In critically ill patients admitted to the ICU for non-cardiac reasons, admission NT-proBNP had the strongest independent association with maximum stage of AKI and need for RRT

Differentiating midazolam over-sedation from neurological damage in the intensive care unit

INTRODUCTION: Midazolam is used routinely to sedate patients in the intensive care unit (ICU). We suspected that midazolam over-sedation was occurring in the ICU of the Guy's and St. Thomas' Trust and that it could be difficult to differentiate this from underlying neurological damage. A sensitive assay for detecting midazolam and 1-hydroxymidazolam glucuronide (1-OHMG) in serum was developed and applied in the clinical setting. METHODS: In the present study we evaluated a series of cases managed in a mixed medical, surgical and trauma ICU. Serum was collected from 26 patients who received midazolam, were 'slow to wake' and in whom there was suspicion of neurological damage. Patient outcome was followed in terms of mortality, neurological recovery and neurological damage on discharge. RESULTS: Out of 26 patients, 13 had detectable serum levels of midazolam and/or 1-OHMG after a median of 67 hours (range 36–146 hours) from midazolam cessation. Of these 13 patients in whom midazolam/1-OHMG was detectable, 10 made a full neurological recovery. Of the remaining 13 patients with no detectable midazolam/1-OHMG, three made a full neurological recovery; 10 patients were subsequently found to have suffered neurological damage (P < 0.002), eight of whom died and two were discharged from the ICU with profound neurological damage. CONCLUSION: These findings confirm that prolonged sedation after midazolam therapy should be considered in the differential diagnosis of neurological damage in the ICU. This can be reliably detected by the assay method described. The effects of midazolam/1-OHMG persist days after administration of midazolam has ceased. After prolonged sedation has been excluded in this patient group, it is highly likely that neurological damage has occurred

The diagnostic and prognostic significance of monitoring blood levels of immature neutrophils in patients with systemic inflammation

INTRODUCTION: In this cohort study, we investigated whether monitoring blood levels of immature neutrophils (myelocytes, metamyelocytes and band cells) differentiated patients with sepsis from those with the non-infectious (N-I) systemic inflammatory response syndrome (SIRS). We also ascertained if the appearance of circulating immature neutrophils was related to adverse outcome. METHODS: Blood samples were routinely taken from 136 critically ill patients within 48 hours of ICU entry and from 20 healthy control subjects. Clinical and laboratory staff were blinded to each other’s results, and patients were retrospectively characterised into those with SIRS (n = 122) and those without SIRS (n = 14). The patients with SIRS were further subdivided into categories of definite sepsis (n = 51), possible sepsis (n = 32) and N-I SIRS (n = 39). Two established criteria were used for monitoring immature white blood cells (WBCs): one where band cells >10% WBCs and the other where >10% of all forms of immature neutrophils were included but with a normal WBC count. Immature neutrophils in blood smears were identified according to nuclear morphology and cytoplasmic staining. RESULTS: With the first criterion, band cells were present in most patients with SIRS (mean = 66%) when compared with no SIRS (mean = 29%; P <0.01) and with healthy subjects (0%). The prevalence of band cells was higher in definite sepsis (mean = 82%) than in patients with possible sepsis (mean = 63%; P <0.05) or with N-I SIRS (mean = 39%; P <0.001), and they had a sensitivity of 84% and a specificity of 71% for the detection of definite sepsis. With the second criterion (that is, patients with normal WBC counts), we noted that immature neutrophils did not differentiate any of the patient groups from one another. Patients who died within 1 week of blood sample provision had higher levels of myelocytes and metamyelocytes (median = 9%; P <0.05) than patients who died at 2 to 4 weeks (median =0.5%). CONCLUSIONS: Raised blood levels of band cells have diagnostic significance for sepsis, provided that measurements are not confined to patients with normal WBC counts, whereas an increased prevalence of myelocytes and metamyelocytes may have prognostic application

Heparin algorithm for anticoagulation during continuous renal replacement therapy

Premature circuit clotting is a problem during continuous renal replacement therapy. We describe an algorithm for individualised anticoagulation with unfractionated heparin based on the patient's risk of bleeding and previous circuit life. The algorithm allows effective and safe nurse-led anticoagulation during continuous renal replacement therapy