Arterial Blood Samples Research Articles

Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction

BackgroundThe aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI).MethodsIn 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score.ResultsThe markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735–0.89], GRACE score AUC: 0.7961 [CI: 0.6965–0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269–0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192–0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016–0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score.ConclusionsInflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.

A semi-automated device rapidly determine circulating blood volume in healthy males and carbon monoxide uptake kinetics of arterial and venous blood.

We examined whether a semi-automated carbon monoxide (CO) rebreathing method accurately detect changes in blood volume (BV) and total hemoglobin mass (tHb). Furthermore, we investigated whether a supine position with legs raised reduced systemic CO dilution time, potentially allowing a shorter rebreathing period. Nineteen young healthy males participated. BV and tHb was quantified by a 10-min CO-rebreathing period in a supine position with legs raised before and immediately after a 900ml phlebotomy and before and after a 900ml autologous blood reinfusion on the same day in 16 subjects. During the first CO-rebreathing, arterial and venous blood samples were drawn every 2 min during the procedure to determine systemic CO equilibrium in all subjects. Phlebotomy decreased (P < 0.001) tHb and BV by 166 ± 24g and 931 ± 247ml, respectively, while reinfusion increased (P < 0.001) tHb and BV by 143 ± 21g and 862 ± 250ml compared to before reinfusion. After reinfusion BV did not differ from baseline levels while tHb was decreased (P < 0.001) by 36 ± 21g. Complete CO mixing was achieved within 6 min in venous and arterial blood, respectively, when compared to the 10-min sample. On an individual level, the relative accuracy after donation for tHb and BV was 102-169% and 55-165%, respectively. The applied CO-rebreathing procedure precisely detect acute BV changes with a clinically insignificant margin of error. The 10-min CO-procedure may be reduced to 6min with no clinical effects on BV and tHb calculation.Notwithstanding, individual differences may be of concern and should be investigated further.

Capillary Blood Gas in Children Hospitalized Due to Influenza Predicts the Risk of Lower Respiratory Tract Infection.

Background: Influenza may impair respiratory exchange in the case of lower respiratory tract infections (LRTIs). Capillary blood gas (CBG) reflects arterial blood values but is a less invasive method than arterial blood sampling. We aimed to retrospectively verify the usefulness of CBG in pediatric influenza. Material and methods: CBG parameters (pH, pCO2, pO2, SatO2) in laboratory confirmed influenza cases hospitalized in 2013–2020 were verified in terms of LRTI, chest X-ray (CXR) performance, radiologically confirmed pneumonia (CXR + Pneumonia), prolonged hospitalization, and intensive care transfer. A theoretical CBG-based model for CXR performance was created and the odds ratios were compared to the factual CXR performance. Results: Among 409 children (aged 13 days–17 years 3/12, median 31 months), the usefulness of CBG decreased with the age. The SatO2 predicted the LRTI with AUC = 0.74 (95%CI: 0.62–0.86), AUC = 0.71 (0.61–0.82), and AUC = 0.602 (0.502–0.702) in children aged <6 months old (mo), 6–23 mo, 24–59 mo, respectively, while pO2 revealed AUC = 0.73 (0.6–0.85), AUC = 0.67 (0.56–0.78), and AUC = 0.601 (0.501–0.702), respectively. The pCO2 predicted the LRTI most precisely in children <6 months with AUC = 0.75 (0.63–0.87), yet not in older children. A high negative predictive value for CXR + Pneumonia was seen for SatO2 < 6 mo (96.7%), SatO2 6–23 mo (89.6%), pO2 < 6 mo (94.3%), pO2 6–23 mo (88.9%). The use of a CBG-driven CXR protocol (based on SatO2 and pO2) would decrease the odds of an unnecessary CXR in children <2 years old (yo) by 84.15% (74.5–90.14%) and 86.15% (66.46–94.28%), respectively. SatO2 and pO2 also predicted a prolonged hospitalization <6 mo AUC = 0.71 (0.59–0.83) and AUC = 0.73 (0.61–0.84), respectively, and in 6–23 mo AUC = 0.66 (0.54–0.78) and AUC = 0.63 (0.52–0.75), respectively. Conclusions: The CBG is useful mainly in children under two years, predicts the risk of LRTI, and can help exclude the risk of CXR + pneumonia. Children under six months of age represent the group that would benefit the most from CBG. A CBG-based protocol for the performance of CXR could significantly decrease the number of unnecessary CXRs.

Feasibility of using abbreviated scan protocols with population-based input functions for accurate kinetic modeling of [18F]-FDG datasets from a long axial FOV PET scanner

BackgroundAccurate kinetic modeling of 18F-fluorodeoxyglucose ([18F]-FDG) positron emission tomography (PET) data requires accurate knowledge of the available tracer concentration in the plasma during the scan time, known as the arterial input function (AIF). The gold standard method to derive the AIF requires collection of serial arterial blood samples, but the introduction of long axial field of view (LAFOV) PET systems enables the use of non-invasive image-derived input functions (IDIFs) from large blood pools such as the aorta without any need for bed movement. However, such protocols require a prolonged dynamic PET acquisition, which is impractical in a busy clinical setting. Population-based input functions (PBIFs) have previously shown potential in accurate Patlak analysis of [18F]-FDG datasets and can enable the use of shortened dynamic imaging protocols. Here, we exploit the high sensitivity and temporal resolution of a LAFOV PET system and explore the use of PBIF with abbreviated protocols in [18F]-FDG total body kinetic modeling.MethodsDynamic PET data were acquired in 24 oncological subjects for 65 min following the administration of [18F]-FDG. IDIFs were extracted from the descending thoracic aorta, and a PBIF was generated from 16 datasets. Five different scaled PBIFs (sPBIFs) were generated by scaling the PBIF with the AUC of IDIF curve tails using various portions of image data (35–65, 40–65, 45–65, 50–65, and 55–65 min post-injection). The sPBIFs were compared with the IDIFs using the AUCs and Patlak Ki estimates in tumor lesions and cerebral gray matter. Patlak plot start time (t*) was also varied to evaluate the performance of shorter acquisitions on the accuracy of Patlak Ki estimates. Patlak Ki estimates with IDIF and t* = 35 min were used as reference, and mean bias and precision (standard deviation of bias) were calculated to assess the relative performance of different sPBIFs. A comparison of parametric images generated using IDIF and sPBIFs was also performed.ResultsThere was no statistically significant difference between AUCs of the IDIF and sPBIFs (Wilcoxon test: P > 0.05). Excellent agreement was shown between Patlak Ki estimates obtained using sPBIF and IDIF. Using the sPBIF55–65 with the Patlak model, 20 min of PET data (i.e., 45 to 65 min post-injection) achieved < 15% precision error in Ki estimates in tumor lesions compared to the estimates with the IDIF. Parametric images reconstructed using the IDIF and sPBIFs with and without an abbreviated protocol were visually comparable. Using Patlak Ki generated with an IDIF and 30 min of PET data as reference, Patlak Ki images generated using sPBIF55–65 with 20 min of PET data (t* = 45 min) provided excellent image quality with structural similarity index measure > 0.99 and peak signal-to-noise ratio > 55 dB.ConclusionWe demonstrate the feasibility of performing accurate [18F]-FDG Patlak analysis using sPBIFs with only 20 min of PET data from a LAFOV PET scanner.

First-in-human use of 11C-CPPC with positron emission tomography for imaging the macrophage colony-stimulating factor 1 receptor

PurposeStudy of the contribution of microglia to onset and course of several neuropsychiatric conditions is challenged by the fact that these resident immune cells often take on different phenotypes and functions outside the living brain. Imaging microglia with radiotracers developed for use with positron emission tomography (PET) allows researchers to study these cells in their native tissue microenvironment. However, many relevant microglial imaging targets such as the 18 kDa translocator protein are also expressed on non-microglial cells, which can complicate the interpretation of PET findings. 11C-CPPC was developed to image the macrophage colony-stimulating factor 1 receptor, a target that is expressed largely by microglia relative to other cell types in the brain. Our prior work with 11C-CPPC demonstrated its high, specific uptake in brains of rodents and nonhuman primates with neuroinflammation, which supports the current first-in-human evaluation of its pharmacokinetic behavior in the brains of healthy individuals.MethodsEight healthy nonsmoker adults completed a 90-min dynamic PET scan that began with bolus injection of 11C-CPPC. Arterial blood sampling was collected in order to generate a metabolite-corrected arterial input function. Tissue time-activity curves (TACs) were generated using regions of interest identified from co-registered magnetic resonance imaging data. One- and two-tissue compartmental models (1TCM and 2TCM) as well as Logan graphical analysis were compared.ResultsCortical and subcortical tissue TACs peaked by 37.5 min post-injection of 11C-CPPC and then declined. The 1TCM was preferred. Total distribution volume (VT) values computed from 1TCM aligned well with those from Logan graphical analysis (t* = 30), with VT values relatively high in thalamus, striatum, and most cortical regions, and with relatively lower VT in hippocampus, total white matter, and cerebellar cortex.ConclusionOur results extend support for the use of 11C-CPPC with PET to study microglia in the human brain.

18F]NOS PET Brain Imaging Suggests Elevated Neuroinflammation in Idiopathic Parkinson's Disease.

Neuroinflammation is implicated as a key pathologic mechanism in many neurodegenerative diseases and is thought to be mediated in large part by microglia, native phagocytic immune cells of the CNS. Abnormal aggregation of the protein α-synuclein after phagocytosis by microglia is one possible neuropathophysiological mechanism driving Parkinson’s disease (PD). We conducted a human pilot study to evaluate the feasibility of targeting the inducible isoform of nitric oxide synthase using the [18F]NOS radiotracer to measure neuroinflammation in idiopathic PD. Ten adults consisting of 6 PD patients and 4 healthy controls (HC) underwent one hour of dynamic [18F]NOS positron emission tomography (PET) brain imaging with arterial blood sampling. We observed increased [18F]NOS whole brain distribution volume (VT) in PD patients compared to age-matched healthy controls (p < 0.008) via a 1-tissue compartment (TC) model. The rate constant K1 for transport from blood into tissue did not differ between groups (p = 0.72). These findings suggest elevated oxidative stress, a surrogate marker of inflammation, is present in early-stage idiopathic PD and indicate that [18F]NOS PET imaging is a promising, non-invasive method to measure neuroinflammation.

Hemodilution on microvascular oxygen delivery potential of the blood during coronary bypass surgery.

The hematocrit-to-whole blood viscosity ratio (Hct/WBV) reflects the blood O2 delivery potential (O2-DP). WBV is variable to the dynamic vascular shear rate (SR), 1-5/s at microcirculation and 300/s at larger vessels. To estimate the impact of hemodilution on the blood O2-DP to the myocardium, we analyzed the hemodilution-induced change of Hct/WBV at SR 5/s (Hct/WBV5) during off-pump coronary bypass (OPCAB) surgery. During OPCAB surgery (n = 21), 10% acute normovolemic hemodilution (HD 10%) was applied. Arterial blood samples were taken: one before and two after HD 10%. One of which after HD 10% underwent an additional 33% in vitro hemodilution (reaching 40% hemodilution in total, HD 40%). WBV of all blood samples was determined using a scan-capillary tube viscometer (Hemovister™). The changes of Hct/WBV5 were analyzed as a primary measure of the study and compared with those of Hct/WBV at SR 300/s (Hct/WBV300). Median[IQR] of Hct/WBV5 [3.5 (2.8-4.2)%/cPoise] was significantly increased by HD 10 and HD 40% [3.6 (3.2-4.6)%/cPoise and 4.2 (3.3-5.2)%/cPoise, respectively, all P < 0.001], but the degrees of changes after HD 10 and HD 40% were not different. Median[IQR] of Hct/WBV300 [10.3(8.6‒10.8)%/cPoise] was not changed by HD 10% [10.3(9.1-11.1)%/cPoise], but it was significantly decreased by HD 40% [8.4(7.4‒9.2)%/cPoise, P < 0.001]. The increased Hct/WBV5 suggests that 10-40% hemodilution improves the blood O2-DP to the myocardium during OPCAB surgery. The SR-specific discrepancy in Hct/WBV changes advocates using microvascular WBV and Hct/WBV to evaluate the blood O2-DP changes to the myocardium. Further study is warranted to assess the actual changes in myocardial O2 delivery.

Quantification of the purinergic P2X7 receptor with [11C]SMW139 improves through correction for brain-penetrating radiometabolites

The membrane-based purinergic 7 receptor (P2X7R) is expressed on activated microglia and the target of the radioligand [11C]SMW139 for in vivo assessment of neuroinflammation. This study investigated the contribution of radiolabelled metabolites which potentially affect its quantification. Ex vivo high-performance liquid chromatography with a radio detector (radioHPLC) was used to evaluate the parent and radiometabolite fractions of [11C]SMW139 in the brain and plasma of eleven mice. Twelve healthy humans underwent 90-min [11C]SMW139 brain PET with arterial blood sampling and radiometabolite analysis. The volume of distribution was estimated by using one- and two- tissue compartment (TCM) modeling with single (VT) and dual (VTp) input functions. RadioHPLC showed three major groups of radiometabolite peaks with increasing concentrations in the plasma of all mice and humans. Two radiometabolite peaks were also visible in mice brain homogenates and therefore considered for dual input modeling in humans. 2TCM with single input function provided VT estimates with a wide range (0.10–10.74) and high coefficient of variation (COV: 159.9%), whereas dual input function model showed a narrow range of VTp estimates (0.04–0.24; COV: 33.3%). In conclusion, compartment modeling with correction for brain-penetrant radiometabolites improves the in vivo quantification of [11C]SMW139 binding to P2X7R in the human brain.

Cerebrospinal fluid and arterial acid–base equilibria in spontaneously breathing third-trimester pregnant women

BackgroundAcid–base status in full-term pregnant women is characterised by hypocapnic alkalosis. Whether this respiratory alkalosis is primary or consequent to changes in CSF electrolytes is not clear. MethodsWe enrolled third-trimester pregnant women (pregnant group) and healthy, non-pregnant women of childbearing age (controls) undergoing spinal anaesthesia for Caesarean delivery and elective surgery, respectively. Electrolytes, strong ion difference (SID), partial pressure of carbon dioxide (PaCO2), and pH were measured in simultaneously collected CSF and arterial blood samples. ResultsAll pregnant women (20) were hypocapnic, whilst only four (30%) of the controls (13) had an arterial PaCO2 <4.7 kPa (P<0.001). The incidence of hypocapnic alkalosis was higher in the pregnant group (65% vs 8%; P=0.001). The CSF-to-plasma Pco2 difference was significantly higher in pregnant women (1.5 [0.3] vs 1.0 [0.4] kPa; P<0.001), mainly because of a decrease in arterial Pco2 (3.9 [0.3] vs 4.9 [0.5] kPa; P<0.001). Similarly, the CSF-to-plasma difference in SID was less negative in pregnant women (–7.8 [1.4] vs –11.4 [2.3] mM; P<0.001), mainly because of a decreased arterial SID (31.5 [1.2] vs 36.1 [1.9] mM; P<0.001). The major determinant of the reduced plasma SID of pregnant women was a relative increase in plasma chloride compared with sodium. ConclusionsPrimary hypocapnic alkalosis characterises third-trimester pregnant women leading to chronic acid–base adaptations of CSF and plasma. The compensatory SID reduction, mainly sustained by an increase in chloride concentration, is more pronounced in plasma than in CSF, as the decrease in Pco2 is more marked in this compartment. Clinical trial registrationNCT03496311.

First-in-human evaluation of [18F]CETO: a novel tracer for adrenocortical tumours

Purpose[11C]Metomidate positron emission tomography (PET) is currently used for staging of adrenocortical carcinoma and for lateralization in primary aldosteronism (PA). Due to the short half-life of carbon-11 and a high non-specific liver uptake of [11C]metomidate there is a need for improved adrenal imaging methods. In a previous pre-clinical study para-chloro-2-[18F]fluoroethyletomidate has been proven to be a specific adrenal tracer. The objective is to perform a first evaluation of para-chloro-2-[18F]fluoroethyletomidate positron emission computed tomography ([18F]CETO-PET/CT) in patients with adrenal tumours and healthy volunteers.MethodsFifteen patients underwent [18F]CETO-PET/CT. Five healthy volunteers were recruited for test-retest analysis and three out of the five underwent additional [15O]water PET/CT to measure adrenal blood flow. Arterial blood sampling and tracer metabolite analysis was performed. The kinetics of [18F]CETO were assessed and simplified quantitative methods were validated by comparison to outcome measures of tracer kinetic analysis.ResultsUptake of [18F]CETO was low in the liver and high in adrenals. Initial metabolization was rapid, followed by a plateau. The kinetics of [18F]CETO in healthy adrenals and all adrenal pathologies, except for adrenocortical carcinoma, were best described by an irreversible single-tissue compartment model. Standardized uptake values (SUV) correlated well with the uptake rate constant K1. Both K1 and SUV were highly correlated to adrenal blood flow in healthy controls. Repeatability coefficients of K1, SUV65–70, and SUV120 were 25, 22, and 17%.ConclusionsHigh adrenal uptake combined with a low unspecific liver uptake suggests that 18F]CETO is a suitable tracer for adrenal imaging. Adrenal SUV, based on a whole-body scan at 1 h p.i., correlated well with the net uptake rate Ki.Trial registrationClinicalTrials.gov, NCT05361083 Retrospectively registered 29 April 2022. at, https://clinicaltrials.gov/ct2/show/NCT05361083

Clinical validation of a population-based input function for 20-min dynamic whole-body 18F-FDG multiparametric PET imaging

PurposeContemporary PET/CT scanners can use 70-min dynamic whole-body (D-WB) PET to generate more quantitative information about FDG uptake than just the SUV by generating parametric images of FDG metabolic rate (MRFDG). The analysis requires the late (50–70 min) D-WB tissue data combined with the full (0–70 min) arterial input function (AIF). Our aim was to assess whether the use of a scaled population-based input function (sPBIF) obviates the need for the early D-WB PET acquisition and allows for a clinically feasible 20-min D-WB PET examination.MethodsA PBIF was calculated based on AIFs from 20 patients that were D-WB PET scanned for 120 min with simultaneous arterial blood sampling. MRFDG imaging using PBIF requires that the area under the curve (AUC) of the sPBIF is equal to the AUC of the individual patient’s input function because sPBIF AUC bias translates into MRFDG bias. Special patient characteristics could affect the shape of their AIF. Thus, we validated the use of PBIF in 171 patients that were divided into 12 subgroups according to the following characteristics: diabetes, cardiac ejection fraction, blood pressure, weight, eGFR and age. For each patient, the PBIF was scaled to the aorta image-derived input function (IDIF) to calculate a sPBIF, and the AUC bias was calculated.ResultsWe found excellent agreement between the AIF and IDIF at all times. For the clinical validation, the use of sPBIF led to an acceptable AUC bias of 1–5% in most subgroups except for patients with diabetes or patients with low eGFR, where the biases were marginally higher at 7%. Multiparametric MRFDG images based on a short 20-min D-WB PET and sPBIF were visually indistinguishable from images produced by the full 70-min D-WB PET and individual IDIF.ConclusionsA short 20-min D-WB PET examination using PBIF can be used for multiparametric imaging without compromising the image quality or precision of MRFDG. The D-WB PET examination may therefore be used in clinical routine for a wide range of patients, potentially allowing for more precise quantification in e.g. treatment response imaging.

Utility of Pulse Oximetry Oxygen Saturation (SpO2) with Incorporation of Positive End-Expiratory Pressure (SpO2 ∗10/FiO2 ∗PEEP) for Classification and Prognostication of Patients with Acute Respiratory Distress Syndrome.

Background Conventionally, PaO2/FiO2 (P/F ratio) has been used to categorize severity of acute respiratory distress syndrome (ARDS) and prognostication of outcome. Recent literature has shown that incorporation of positive end-expiratory pressure (PEEP) into the P/F ratio (PaO2∗10/FiO2∗PEEP or P/FP∗10) has a much better prognostic ability in ARDS as compared to P/F ratio. The aim of this study was to correlate SpO2∗10/FiO2∗PEEP (S/FP∗10) to PaO2∗10/FiO2∗PEEP (P/FP∗10) and evaluate the utility of S/FP∗10 as a reliable noninvasive indicator of oxygenation in ARDS to avoid repeated arterial blood sampling. Aim To evaluate if pulse oximetry is a reliable indicator of oxygenation in ARDS patients by calculating SpO2∗10/FiO2∗PEEP (S/FP∗10). The primary objective was to determine the correlation of S/FP∗10 to P/FP∗10 ratio in ARDS patients. The secondary objective was to determine the cut-off value of S/FP∗10 ratio to predict severe ARDS and survival. Methods Patients aged 18–80 years on invasive mechanical ventilation (MV) diagnosed with ARDS as defined by the Berlin definition were included. The values of PaO2, FiO2, and SpO2 were collected at three different time points. They were at baseline, i.e., after intubation and initiation of MV (within one hour of intubation), day one (1–24 hours of MV), and day three (48–72 hours of MV). The primary outcome was survival at the end of intensive care unit (ICU) stay. Results A total of 85 patients with ARDS on invasive MV were included. The data points were obtained at baseline, day one, and day three of MV. S/FP∗10 ratio has an excellent correlation to P/FP∗10 ratio at baseline and day three of invasive MV (r = 0.831 and 0.853, respectively; p < 0.001) and has a strong correlation on day one of invasive MV (r = 0.733, p < 0.001). S/FP∗10 ratio ≤116 at baseline has excellent discriminant function to be categorized as severe ARDS as per Berlin definition (AUC: 0.925, p < 0.001, 90% sensitivity, 93% specificity, CI: [0.862–0.988]). The increase in S/FP∗10 ratio by ≥64.40 from baseline to day three of MV is a good predictor of survival (AUC: 0.877, p < 0.001, 73.5% sensitivity, 97% specificity, CI: [0.803–0.952]). Conclusion S/FP∗10 has a strong correlation to P/FP∗10 in ARDS patients. S/FP∗10 ≤116 has an excellent discriminant function to be categorized as severe ARDS. The S/FP∗10 ratio on day three of MV and the change in S/FP∗10 ratio from baseline and day one to day three of MV are good predictors of survival in ARDS patients. This trial is registered with CTRI/2020/04/024940.

Effect of dialysate bicarbonate and sodium on blood pH in maintenance hemodialysis-A prospective study.

The validity of adjusting dialysate bicarbonate based on pre-hemodialysis (HD) serum bicarbonate is unclear. There are no studies of the impact of dialysate sodium on blood pH. To understand the impact of dialysate bicarbonate and sodium on blood pH. Two hundred arterialized blood samples were obtained on the third session of HD with four configurations of dialysate: sodium (140, 137 mEq/L) and bicarbonate (38, 32 mEq/L). The correlation between pre-HD serum bicarbonate and pH was modest (r=0.6). A lower dialysate sodium (p=0.035) and a higher bicarbonate (p=0.02) associated with a higher post-HD blood pH. The frequency of pre-HD blood pH of <7.4 and a post-HD blood pH of >7.5 did not differ for samples with serum bicarbonate <22, 22-26, or >26 mEq/L. Adjusting dialysate buffer based on pre-HD serum bicarbonate is unnecessary. A higher bicarbonate and lower dialysate sodium associate with post-HD alkalemia.

Essential amino acid profile of supplemental metabolizable protein affects mammary gland metabolism and whole-body glucose kinetics in dairy cattle.

This study investigated mammary gland metabolism and whole-body (WB) rate of appearance (Ra) of glucose in dairy cattle in response to a constant supplemental level of metabolizable protein (MP) composed of different essential AA (EAA) profiles. Five multiparous rumen-fistulated Holstein-Friesian dairy cows (2.8 ± 0.4 lactations; 81 ± 11 d in milk; mean ± standard deviation) were abomasally infused according to a 5 × 5 Latin square design with saline (SAL) or 562 g/d of EAA delivered in different profiles where individual AA content corresponded to their relative content in casein. The profiles consisted of (1) a complete EAA mixture (EAAC), (2) Ile, Leu, and Val (ILV), (3) His, Ile, Leu, Met, Phe, Trp, Val (GR1+ILV), and (4) Arg, His, Lys, Met, Phe, Thr, Trp (GR1+ALT). A total mixed ration (58% corn silage, 16% alfalfa hay, and 26% concentrate on a dry matter basis) was formulated to meet 100 and 83% of net energy and MP requirements, respectively, and was fed at 90% of ad libitum intake on an individual cow basis. Each experimental period consisted of 5 d of continuous abomasal infusion followed by 2 d of no infusion. Arterial and venous blood samples were collected on d 4 of each period for determination of mammary gland AA and glucose metabolism. On d 5 of each period, D-[U-13C]glucose (13 mmol priming dose; continuous 3.5 mmol/h for 520 min) was infused into a jugular vein and arterial blood samples were collected before and during infusion to determine WB Ra of glucose. Milk protein yield did not differ between EAAC, GR1+ILV, and GR1+ALT, or between SAL and ILV, and increased over SAL and ILV with EAAC and GR1+ILV. Mammary plasma flow increased with ILV infusion compared with EAAC and GR1+ILV. Infusion of EAAC tended to increase mammary gland net uptake of total EAA and decreased the mammary uptake to milk protein output ratio (U:O) of non-EAA compared with SAL. Infusion of ILV increased mammary net uptake and U:O of Ile, Leu, and Val markedly over all treatments. The U:O of total Ile, Leu, and Val increased numerically (25%) with GR1+ILV infusion compared with EAAC, and the U:O of total Arg, Lys, and Thr tended to decrease, primarily from decreased U:O of Lys. During GR1+ALT infusion, U:O of total Arg, Lys, and Thr was greater than that during EAAC infusion, whereas U:O of Ile, Leu, and Val did not differ from EAAC. Glucose WB Ra increased 16% with GR1+ALT over SAL, and increased numerically 8 and 12% over SAL with EAAC and GR1+ILV, respectively. The average proportion of lactose yield relative to glucose WB Ra did not differ across treatments and averaged 0.53. On average, 28% of milk galactose arose from nonglucose precursors, regardless of treatment. In conclusion, intramammary catabolism of group 2 AA increased to support milk component synthesis when the EAA profile of MP was incomplete with respect to casein. Further, WB and mammary gland glucose metabolism was flexible in support of milk component synthesis, regardless of absorptive EAA profile.

Pharmacokinetics of Sustained-release and Extended-release Buprenorphine in Mice after Surgical Catheterization.

The Guide for the Care and Use of Laboratory Animals strongly encourages the use of pharmaceutical-grade chemicals and analgesics. Sustained-release buprenorphine (SRB) is administered extralabel to rodents to mitigate moderate to severe pain. An FDA-indexed buprenorphine formulation-extended-release buprenorphine (XRB)-has recently become available and is currently the only pharmaceutical-grade slow-release buprenorphine formulation approved for use in mice and rats. However, no studies have directly compared the pharmacokinetic parameters of SRB and XRB in surgically catheterized mice. To this end, we compared the plasma buprenorphine concentrations and pharmacokinetic parameters of SRB and XRB in mice after surgical catheterization. We hypothesized that mice treated before surgery with SRB or XRB would have circulating buprenorphine concentrations that exceeded the therapeutic threshold for as long as 72 h after surgery. Male and female C57Bl/6J mice were anesthetized, treated with a single dose of either SRB (1 mg/kg SC) or XRB (3.25 mg/kg SC), and underwent surgical catheterization. Arterial blood samples were collected at 6, 24, 48, and 72 h after administration. Weight loss after surgery (mean ± SEM) was similar between groups (SRB: males, 12% ± 2%; females, 8% ± 2%; XRB: males, 12% ± 1%; females, 8% ± 1%). Both SRB and XRB maintained circulating buprenorphine concentrations above the therapeutic level of 1.0 ng/mL for 72 h after administration. Plasma buprenorphine concentrations at 6, 24, and 48 h were significantly greater (3- to 4-fold) with XRB than SRB, commensurate with XRB's higher dose. These results support the use of either SRB or XRB for the alleviation of postoperative pain in mice. The availability of FDA-indexed XRB increases options for safe and effective pharmaceutical-grade analgesia in rodents.

Reliability of pulse oximetry at four different attachment sites in immobilized white rhinoceros (Ceratotherium simum)

ObjectivesTo determine the reliability of peripheral oxygen haemoglobin saturation (SpO2), measured by a Nonin PalmSAT 2500A pulse oximeter with 2000T transflectance probes at four attachment sites (third eyelid, cheek, rectum and tail), by comparing these measurements to arterial oxygen haemoglobin saturation (SaO2), measured by an AVOXimeter 4000 co-oximeter reference method in immobilized white rhinoceros (Ceratotherium simum). Study designRandomized crossover study. AnimalsA convenience sample of eight wild-caught male white rhinoceros. MethodsWhite rhinoceros were immobilized with etorphine (0.0026 ± 0.0002 mg kg–1, mean ± standard deviation) intramuscularly, after which the pinna was aseptically prepared for arterial blood sample collection, and four pulse oximeters with transflectance probes were fixed securely to their attachment sites (third eyelid, cheek, rectum and tail). At 30 minutes following recumbency resulting from etorphine administration, the animals were given either butorphanol (0.026 ± 0.0001 mg kg–1) or an equivalent volume of saline intravenously. At 60 minutes following recumbency, insufflated oxygen (15 L minute–1 flow rate) was provided intranasally. In total, the SpO2 paired measurements from the third eyelid (n = 80), cheek (n = 67), rectum (n = 59) and tail (n = 76) were compared with near-simultaneous SaO2 measurements using Bland-Altman to assess bias (accuracy), precision, and the area root mean squares (ARMS) method. ResultsCompared with SaO2, SpO2 measurements from the third eyelid were reliable (i.e., accurate and precise) above an SaO2 range of 70% (bias = 1, precision = 3, ARMS = 3). However, SpO2 measurements from the cheek, rectum and tail were unreliable (i.e., inaccurate or imprecise). Conclusions and clinical relevanceA Nonin PalmSAT pulse oximeter with a transflectance probe inserted into the space between the third eyelid and the sclera provided reliable SpO2 measurements when SaO2 was > 70%, in immobilized white rhinoceros.

Cervical sympathetic trunk transection alleviates acute lung injury caused by intestinal obstruction via inhibition of phospholipase A2 in rats

BackgroundIntestinal obstruction can result in inflammatory injury to distant organs, especially the lungs. Stellate ganglion block (SGB) provides sympathetic nervous homeostasis and inhibits the systemic inflammatory response. This study aimed to investigate whether SGB can alleviate acute lung injury by inhibiting phospholipase A2 expression in rats.MethodsThirty healthy male Sprague–Dawley rats were divided into three groups: C group (sham-operated); CLP group (cecal ligation and puncture with intestinal obstruction), and cervical sympathetic trunk transection (CSTT) group (transection of the cervical sympathetic trunk following CLP).Arterial blood samples were obtained to determine the ratio of partial arterial pressure of oxygen (PaO2) to fraction of oxygen in inspired air (FiO2). Venous blood samples were used to evaluate the serum concentrations of chemokines, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10 using enzyme-linked immunosorbent assays. Following euthanasia, the lungs were isolated to estimate the wet/dry lung weight (W/D) ratio, evaluate the pathological damage to lung tissues on microscopy, and determine secretory-type phospholipase A2 (sPLA2) expression using western blotting.ResultsRats in the CLP group showed increased fatigue, decreased activity levels, and coarse, gray hair. The levels of chemokines, TNF-α, and IL-6 in the CLP and CSTT groups were higher than those in the C group. However, the levels were lower in the CSTT group than those in the CLP group. IL-10 levels in the CLP group were higher and lower than those in the C and CSTT groups, respectively. W/D ratios and PaO2/FiO2 in the CLP and CSTT groups were higher than those in the C group, whereas these ratios in the CSTT group were lower than those in the CLP group. No lung injury was noted in group C, and the lung injury scores were lower in the CSTT group than those in the CLP group. sPLA2 expression levels in the CLP group were higher than those in the C group, whereas these levels in the CSTT group were lower than those in the CLP group.ConclusionssPLA2 overexpression in the lungs may be a pathogenic factor in acute lung injury. CSTT alleviated acute lung injury by inhibiting sPLA2 expression.

The Association Between Serum Lactate Concentration, Base Deficit, and Mortality in Polytrauma Patients as a Prognostic Factor: An Observational Study.

IntroductionIn polytrauma patients, it is crucial to identify the severity of the injuries to ensure patient safety and survival. Polytrauma leads to hypotension and hypoperfusion, which results in an anaerobic metabolism with acidosis and a decrease in base excess. Thus, blood lactate levels above a certain threshold indicate the existence of global tissue hypoxia, which is a precursor to shock and multiple organ dysfunction syndrome (MODS). The serum lactate and base deficit (BD) levels are used in polytrauma patients as measures of damage severity and resuscitation endpoints and as a way to evaluate therapy efficacy and to predict outcomes. Thus, arterial blood gas analysis is of great value in assessing the status and prognosis of patients with polytrauma. There are few comparative studies on the predictive values of these markers in trauma patients. To determine which measure can more accurately predict the prognosis of polytrauma patients, the present study investigated the predictive values of mortality of these indicators for mortality within 48 hours of admission to the emergency room (ER) in patients with polytrauma.MethodsThis prospective study was designed for a single tertiary care center in northern India. We included 90 patients with polytrauma who were between the ages of 18 and 70 years, with the exception of pregnant women, who presented to the ER within six hours of injury with an injury severity score (ISS) >16, serum lactate level >2.0 mmol/L, and BD -4.0 mEq/L at the time of admission. If the patient's ISS was >16 at the time of ER presentation, arterial blood samples were drawn to determine the serum lactate and BD level at the time of admission and at 12, 24, and 48 hours intervals after ER admission. The primary outcome was the change in serum lactate and BD level in polytrauma. The secondary outcomes were an association of serum lactate and BD with mortality and the correlation between serum lactate with the BD and ISS with mortality of polytrauma patients. The timing of all outcome assessments was at 48 hours after each patient's ER admission.ResultsLactate clearance from 0-12 hours (t = 2.28, p <0.05), 0-24 hours (t = 6.01, p <0.001), and 0-48 hours (t = 7.98, p <0.001) and a correction in BD from 0-24 (t = 2.68, p <0.01 ) and 0-48 hours (t = 5.46, p <0.001) were significantly higher in nonsurvivors as compared with survivors. In survivors and nonsurvivors, mean serum lactate levels (2.46 ± 1.46 versus 4.15 ± 2.99, t = 3.31, p <0.001, 95%Cl) and mean BD (-3.17 ± 2.58 versus -6.5 ± 4.91, t = 3.86, p <0.001, 95%CI) had a statistically significant difference. The serum lactate and BD levels at time of ER admission (r L0, BD0 = -0.765, p <0.01) and 48 hours after ER admission (r L48, BD 48 = -0.652, p <0.001) were highly negatively correlated.ConclusionIn polytrauma patients, serum lactate and BD are simple, quick, and independent biochemical predictors of 48-hour mortality, and this single arterial blood test would thereby improve decision-making for resuscitation effectiveness. Prolonged lactate and BD normalization time were associated with higher mortality. Serum lactate and BD are negatively correlated. A higher ISS at admission was associated with a higher incidence of mortality in polytrauma patients.

Arterial and venous blood sampling is equally applicable for coagulation and fibrinolysis analyses.

No consensus exists upon whether arterial and venous blood samples are equivalent when it comes to coagulation analyses. We therefore conducted a comparative cohort study to clarify if arteriovenous differences affect analyses of primary and secondary hemostasis as well as fibrinolysis. Simultaneous paired blood samplings were obtained from a cannula in the radial artery and an antecubital venipuncture in 100 patients immediately before or one day after thoracic surgery. Analyses of platelet count and aggregation, International Normalized Ratio (INR), activated partial thromboplastin time (APTT), antithrombin, thrombin time, fibrinogen, D-dimer, rotational thromboelastometry (ROTEM), thrombin generation, prothrombin fragment 1+2, and an in-house dynamic fibrin clot formation and lysis assay were performed. No differences were found between arterial and venous samples for the far majority of parameters. The only differences were found in INR, median (IQR): venous, 1.1 (0.2) vs. arterial, 1.1 (0.2) (p<0.002) and in prothrombin fragment 1+2: venous, 289 (209) pmol/L vs. arterial, 279 (191) pmol/L (p<0.002). The sampling site does not affect the majority of coagulation analyses. Small differences were found for two parameters. Due to numerically very discrete differences, they are of no clinical relevance. In conclusion, the present data suggest that both samples obtained from arterial and venous blood may be applied for analyses of coagulation and fibrinolysis.

Acid–Base Abnormalities among Patients Admitted in the Intensive Care Unit of a Teaching Hospital

Abstract Acid–base abnormalities (arterial blood gas [ABG]) pose a threat to survival in intensive care unit (ICU) patients. We present a case series of 60 cases from hospital records highlighting the acid–base abnormalities among ICU patients. All standard protocols were followed in the study hospital to collect the arterial blood samples and standard procedures for measurement of ABGs. We found that 93.3% had acid–base abnormalities, 13.3% had nonanion gap metabolic acidosis, 20% had anion gap metabolic acidosis, 50% had metabolic alkalosis, 45% had respiratory acidosis, 21.7% had respiratory alkalosis, 41.7% had mixed disorders, 31.7% had double disorders, and 10% had triple disorder. We conclude that mixed disorder is common in ICU patients with alkalosis being slightly more common than acidosis. By doing ABG, we will be able to detect the underlying acid–base disorder promptly and initiate treatment immediately so that we can decrease the suffering and save the lives of the patients. Hence, a careful look at the ABG within 24 h of admission of a patient to ICU can help save lives.