In vitro – in vivo correlation (IVIVC) allows prediction of in vivo drug deposition from a nasally inhaled drug based on in vitro drug measurements. In vitro measurements include physical particle ...characterization and, more recently, deposition studies using anatomical models. Currently, there is a lack of IVIVC for deposition measurements in anatomical models, especially for deposition patterns in various nasal cavity regions. Therefore, improvement of in vitro and in vivo measurement methods and knowledge about nasal deposition mechanisms should help IVIVC in the future.
In vitro parameters to be considered to predict in vivo nasal drug deposition: Particle characteristics generated by drug delivery devices, patient ventilation and anatomy using anatomical model tools, for example. Display omitted
Acute brain injury (ABI) covers various clinical entities that may require invasive mechanical ventilation (MV) in the intensive care unit (ICU). The goal of MV, which is to protect the lung and the ...brain from further injury, may be difficult to achieve in the most severe forms of lung or brain injury. This narrative review aims to address the respiratory issues and ventilator management, specific to ABI patients in the ICU.
Since arrhythmia induces irregular pulse waves, it is widely considered to cause flawed oscillometric brachial cuff measurements of blood pressure (BP). However, strong data are lacking. We assessed ...whether the agreement of oscillometric measurements with intra-arterial measurements is worse during arrhythmia than during regular rhythm.
Among patients of three intensive care units (ICUs), a prospective comparison of three pairs of intra-arterial and oscillometric BP readings was performed among patients with arrhythmia and an arterial line already present. After each inclusion in the arrhythmia group, one patient with regular rhythm was included as a control. International Organization for Standardization (ISO) standard validation required a mean bias <5 (sd 8) mm Hg.
In 135 patients with arrhythmia, the agreement between oscillometric and intra-arterial measurements of systolic, diastolic and mean BP was similar to that observed in 136 patients with regular rhythm: for mean BP, similar mean bias −0.1 (sd 5.2) and 1.9 (sd 5.9) mm Hg. In both groups, the ISO standard was satisfied for mean and diastolic BP, but not for systolic BP (sd >10 mm Hg) in our ICU population. The ability of oscillometry to detect hypotension (systolic BP <90 mm Hg or mean BP <65 mm Hg), response to therapy (>10% increase in mean BP after cardiovascular intervention) and hypertension (systolic BP >140 mm Hg) was good and similar during arrhythmia and regular rhythm (respective areas under the receiver operating characteristic curves ranging from 0.89 to 0.96, arrhythmia vs regular rhythm between-group comparisons all associated with P>0.3).
Contrary to widespread belief, arrhythmia did not cause flawed automated brachial cuff measurements.
During fluid challenge, volume expansion (VE)-induced increase in cardiac output (ΔVECO) is seldom measured.
In patients with shock undergoing strictly controlled mechanical ventilation and receiving ...VE, we assessed minimally invasive surrogates for ΔVECO (by transthoracic echocardiography): fluid-induced increases in end-tidal carbon dioxide (ΔVEE′CO2); pulse (ΔVEPP), systolic (ΔVESBP), and mean systemic blood pressure (ΔVEMBP); and femoral artery Doppler flow (ΔVEFemFlow). In the absence of arrhythmia, fluid-induced decrease in heart rate (ΔVEHR) and in pulse pressure respiratory variation (ΔVEPPV) were also evaluated. Areas under the receiver operating characteristic curves (AUCROCs) reflect the ability to identify a response to VE (ΔVECO ≥15%).
In 86 patients, ΔVEE′CO2 had an AUCROC=0.82 interquartile range 0.73–0.90, significantly higher than the AUCROC for ΔVEPP, ΔVESBP, ΔVEMBP, and ΔVEFemFlow (AUCROC=0.61–0.65, all P <0.05). A value of ΔVEE′CO2 >1 mm Hg (>0.13 kPa) had good positive (5.0 2.6–9.8) and fair negative (0.29 0.2–0.5) likelihood ratios. The 16 patients with arrhythmia had similar relationships between ΔVEE′CO2 and ΔVECO to patients with regular rhythm (r2=0.23 in both subgroups). In 60 patients with no arrhythmia, ΔVEE′CO2 (AUCROC=0.84 0.72–0.92) outperformed ΔVEHR (AUCROC=0.52 0.39–0.66, P<0.05) and tended to outperform ΔVEPPV (AUCROC=0.73 0.60–0.84, P=0.21). In the 45 patients with no arrhythmia and receiving ventilation with tidal volume <8 ml kg−1, ΔVEE′CO2 performed better than ΔVEPPV, with AUCROC=0.86 0.72–0.95 vs 0.66 0.49–0.80, P=0.02.
ΔVEE′CO2 outperformed ΔVEPP, ΔVESBP, ΔVEMBP, ΔVEFemFlow, and ΔVEHR and, during protective ventilation, arrhythmia, or both, it also outperformed ΔVEPPV. A value of ΔVEE′CO2 >1 mm Hg (>0.13 kPa) indicated a likely response to VE.
Background
Information is limited regarding the prevalence, management, and outcome of hypoxemia among intensive care unit (ICU) patients. We assessed the prevalence and severity of hypoxemia in ICU ...patients and analyzed the management and outcomes of hypoxemic patients.
Methods
This is a multinational, multicenter, 1-day point prevalence study in 117 ICUs during the spring of 2016. All patients hospitalized in an ICU on the day of the study could be enrolled. Hypoxemia was defined as a PaO
2
/FiO
2
ratio ≤ 300 mmHg and classified as mild (PaO
2
/FiO
2
between 300 and 201), moderate (PaO
2
/FiO
2
between 200 and 101), and severe (PaO
2
/FiO
2
≤ 100 mmHg).
Results
Of 1604 patients included, 859 (54%, 95% CI 51–56%) were hypoxemic, 51% with mild (
n
= 440), 40% with moderate (
n
= 345), and 9% (
n
= 74) with severe hypoxemia. Among hypoxemic patients, 61% (
n
= 525) were treated with invasive ventilation, 10% (
n
= 84) with non-invasive ventilation, 5% (
n
= 45) with high-flow oxygen therapy, 22% (
n
= 191) with standard oxygen, and 1.6% (
n
= 14) did not receive oxygen. Protective ventilation was widely used in invasively ventilated patients. Twenty-one percent of hypoxemic patients (
n
= 178) met criteria for acute respiratory distress syndrome (ARDS) including 65 patients (37%) with mild, 82 (46%) with moderate, and 31 (17%) with severe ARDS. ICU mortality was 27% in hypoxemic patients and significantly differed according to severity: 21% in mild, 26% in moderate, and 50% in patients with severe hypoxemia,
p
< 0.001. Multivariate Cox regression identified moderate and severe hypoxemia as independent factors of ICU mortality compared to mild hypoxemia (adjusted hazard ratio 1.38 1.00–1.90 and 2.65 1.69–4.15, respectively).
Conclusions
Hypoxemia affected more than half of ICU patients in this 1-day point prevalence study, but only 21% of patients had ARDS criteria. Severity of hypoxemia was an independent risk factor of mortality among hypoxemic patients.
Trial registration
NCT 02722031
Antibiotic nebulization theoretically allows the delivery of high doses to the lungs together with limited systemic exposure and toxicity. This study aimed to describe amikacin pharmacokinetics, and ...especially its absorption, in patients treated with high-dose nebulized amikacin.
Twenty critically ill patients experiencing ventilator-associated pneumonia received a 20 mg/kg infusion of amikacin, followed by either three other infusions or three nebulizations of 60 mg/kg amikacin. An extensive sampling regimen allowed measurement of amikacin serum concentrations at 0.5, 1, 1.5, 2, 3, 4, 6, 10 and 24 h after each administration. Amikacin pharmacokinetics was studied by population compartmental modelling.
Amikacin pharmacokinetics was best described using a two-compartment structural model with first-order distribution and elimination, in which lung absorption was described using a transit model. Estimated means (interindividual variability) of the main parameters were: bioavailability F = 2.65% (22.1%); transit compartments n = 1.58 (fixed); transit constant k
= 1.38 h
(33.4%); central volume V
= 10.2 L (10.5%); and elimination constant k
= 0.488 h
(35.8%). The addition of interoccasion variability on F (44.0%) and k
(41.7%) allowed the description of intraindividual variability of bioavailability and elimination. Amikacin clearance was positively correlated with baseline creatinine clearance.
Our pharmacokinetic model provided an accurate description of amikacin concentrations following nebulization. There was wide interindividual and interoccasion variability in the absorption and elimination of amikacin. Nevertheless, systemic exposure after nebulization was always much lower than after infusion, an observation suggesting that nebulized high doses are safe in this regard and may be used to treat ventilator-associated pneumonia.
Abstract
A dry-core idealized general circulation model with a stratospheric polar vortex in the Northern Hemisphere is run with a combination of simplified topography and imposed tropospheric ...temperature perturbations, each located in the Northern Hemisphere with a zonal wavenumber of 1. The phase difference between the imposed temperature wave and the topography is varied to understand what effect this has on the occurrence of polar vortex displacements. Geometric moments are used to identify the centroid of the polar vortex for the purposes of classifying whether or not the polar vortex is displaced. Displacements of the polar vortex are a response to increased tropospheric wave activity. Compared to a model run with only topography, the likelihood of the polar vortex being displaced increases when the warm region is located west of the topography peak, and decreases when the cold region is west of the topography peak. This response from the polar vortex is due to the modulation of vertically propagating wave activity by the temperature forcing. When the southerly winds on the western side of the topographically forced anticyclone are collocated with warm- or cold-temperature forcing, the vertical wave activity flux in the troposphere becomes more positive or negative, respectively. This is in line with recent reanalysis studies that showed that anomalous warming west of the surface pressure high, in the climatological standing wave, precedes polar vortex disturbances.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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