Evaluation of Basis Function and Linear Least Squares Methods for Generating Parametric Blood Flow Images Using <Superscript>15</Superscript>O-Water and Positron Emission Tomography

Purpose Parametric analysis of ¹⁵O-water positron emission tomography (PET) studies allows determination of blood flow (BF), perfusable tissue fraction (PTF), and volume of distribution (V _d) with high spatial resolution. In this paper the performance of basis function and linear least squares methods for generating parametric flow data were evaluated. Procedures Monte Carlo simulations were performed using typical perfusion values for brain, tumor, and heart. Clinical evaluation was performed using seven cerebral and 10 myocardial ¹⁵O-water PET studies. Basis function (BFM), linear least squares (LLS), and generalized linear least squares (GLLS) methods were used to calculate BF, PTF, or V _d. Results Monte Carlo simulations and human studies showed that, for low BF values (<1 ml/min/ml), BF, PTF, and V _d were calculated with accuracies better than 5% for all methods tested. For high BF (>2 ml/min/ml), use of BFM provided more accurate V _d compared with (G)LLS. Conclusions In general, BFM provided the most accurate estimates of BF, PTF, and V _d.     

3′-Deoxy-3′-[F-18]Fluorothymidine Positron Emission Tomography in Patients with Recurrent Glioblastoma Multiforme: Comparison with Gd-DTPA Enhanced Magnetic Resonance Imaging

Introduction The accumulation of 3′-deoxy-3′-[F-18]fluorothymidine (FLT) on positron emission tomography (PET) images in patients with glioblastoma multiforme was evaluated and correlated with gadopentetate dimeglumine (Gd-DTPA) enhancement in magnetic resonance images (MRIs).Methods FLT studies in 10 patients with recurrent glioblastoma multiforme were retrospectively investigated. Dynamic emission data were acquired for 60 minutes immediately after injection of FLT. The standardized uptake value (SUV) for tumor and reference tissue (contralateral hemisphere and ipsilateral cerebellum) was calculated. The volumes of the metabolically active part of the tumor (V _PET) and that of the Gd-DTPA enhancing part of the tumor (V _MR) were calculated.Results FLT uptake in tumors peaked before 5 minutes and sometimes as early as 0.5 minutes, and reached a constant level at approximately 10 minutes after injection. The reference tissue time–activity curves had an early peak and reached a constant low background level. All tumors had increased FLT uptake and showed Gd-DTPA enhancement. The SUV in tumor was significantly higher than that in the reference tissue (P<0.0001). A significant correlation between V _PET and V _MR was found (P<0.0001) although there was a difference in the areas of Gd-DTPA enhancement and FLT uptake.Conclusion These preliminary results indicate that FLT-PET may be useful for the detection of recurrent glioblastoma multiforme. Our data in a relatively small patient population do not support a clear-cut relationship between FLT accumulation and Gd-DTPA enhancement. Further pathologic correlation will determine if it can be used for detecting recurrent tumoral disease.     

动态增强MRI鉴别诊断不典型乳腺癌与纤维腺瘤

目的 探讨动态增强MRI（DCE-MRI）定量参数对不典型乳腺癌和纤维腺瘤的鉴别诊断价值。方法 收集经病理证实的不典型乳腺癌30例（不典型乳腺癌组）和纤维腺瘤32例（纤维腺瘤组）患者。对所有患者均进行DCE-MR检查,获取血流动力学参数容量转移常数（K_trans）、速率常数（K_ep）、血管外细胞外间隙容积分数（V_e）、血浆分数（V_p）,比较两组各参数的统计学差异,并评价其诊断效能。结果 不典型乳腺癌组K_trans、K_ep、V_e、V_p分别为（1.49±0.55）min^-1、（0.70±0.02）min^-1、0.78±0.19、0.26±0.13,纤维腺瘤组K_trans、K_ep、V_e、V_p分别为（0.64±0.23）min^-1、（0.30±0.23）min^-1、0.63±0.25、0.33±0.14;两组间K_trans、V_e、K_ep差异有统计学意义（P均<0.01）,V_p差异无统计学意义（P=0.05）。K_trans、K_ep、V_e诊断不典型乳腺癌和纤维腺瘤的曲线下面积分别为0.94、0.88、0.68,敏感度为86.7%、86.7%、83.3%,特异度为93.7%、81.2%、46.9%。结论 DCE-MRI可准确评估病变的微循环,对纤维腺瘤和不典型乳腺癌的诊断及鉴别诊断具有较高的临床应用价值。     

CT灌注成像对骨巨细胞瘤潜恶性的识别

目的通过临床骨巨细胞瘤的检查，分析各CT灌注参数、最大强化速率（MER）与肿瘤的微血管密度（MVD）的关系；探讨MER在骨巨细胞瘤诊断中的应用价值；评价边缘-中心血流量差异率（Rrim-cen BF）、边缘-中心血容量差异率（Rrim-cen BV）在良恶性骨巨细胞瘤鉴别诊断中的应用价值。方法对24例病人的骨巨细胞瘤行CT灌注检查，其中恶性骨巨细胞瘤14例，良性骨巨细胞瘤10例。术后病理标本常规组织切片及SP免疫组织化学检查，单克隆抗CD34抗体标记血管，用Weidner技术计算肿瘤MVD。分析BF、BV、MER与肿瘤微血管密度的相关性；分析良恶性骨巨细胞瘤外周区与中央区之间BF、BV有无差异；比较良恶性骨肿瘤之间MER、Rrim-cen BF、Rrim-cen BV的差异。结果24例骨巨细胞瘤均表现为高灌注，BF和BV图像上均可清楚显示肿瘤；骨巨细胞瘤的BF、BV和MER与MVD均呈正线性相关。MER能够准确地反映组织的血管化程度，但MER在良恶性骨巨细胞瘤之间存在较多重叠。Rrim-cen BF和Rrim-cen BV值在良恶性骨巨细胞瘤之间的差异具有最著性意义（P〈0．01）。Rrim-cen BF和Rrim-cen BV鉴别良恶性骨肿瘤的阈值分别为Rrim-cen BF：0．15（敏感度：94．4％；特异度：85．7％）；Rrim-cen BV：0．07（敏感度：88．9％；特异度：78．5％）。结论MER可以客观定量地评估骨巨细胞瘤的血供情况，但不能单独应用作为鉴别良恶性骨巨细胞瘤的指标。Rrim-cen BF和Rrim-cen BV为骨巨细胞瘤良恶性鉴别提供了一种有价值的客观定量的影像学检测指标。     

In vivo Breast Sound-Speed Imaging with Ultrasound Tomography

We discuss a bent-ray ultrasound tomography algorithm with total-variation (TV) regularization. We have applied this algorithm to 61 in vivo breast datasets collected with our in-house clinical prototype for imaging sound-speed distributions in the breast. Our analysis showed that TV regularization could preserve sharper lesion edges than the classic Tikhonov regularization. Furthermore, the image quality of our TV bent-ray sound-speed tomograms was superior to that of the straight-ray counterparts for all types of breasts within BI-RADS density categories 1 through 4. Our analysis showed that the improvements for average sharpness (in the unit of (m · s)⁻¹) of lesion edges in our TV bent-ray tomograms are between 2.1 to 3.4-fold compared with the straight ray tomograms. Reconstructed sound-speed tomograms illustrated that our algorithm could successfully image fatty and glandular tissues within the breast. We calculated the mean sound-speed values for fatty tissue and breast parenchyma as 1422 ± 9 m/s (mean ± SD) and1487 ± 21 m/s, respectively. Based on 32 lesions in a cohort of 61 patients, we also found that the mean sound-speed for malignant breast lesions (1548 ± 17 m/s) was higher, on average, than that of benign ones (1513 ± 27 m/s) (one-sided p < 0.001). These results suggest that, clinically, sound-speed tomograms can be used to assess breast density (and therefore, breast cancer risk), as well as detect and help differentiate breast lesions. Finally, our sound-speed tomograms may also be a useful tool to monitor the clinical response of breast cancer patients to neo-adjuvant chemotherapy. (E-mail: lic@karmanos.org)     

Image reconstruction affects computer tomographic assessment of lung hyperinflation

Objectives  Lung hyperinflation may be assessed by computed tomography (CT). As shown for patients with emphysema, however, CT image reconstruction affects quantification of hyperinflation. We studied the impact of reconstruction parameters on hyperinflation measurements in mechanically ventilated (MV) patients. Design  Observational analysis. Setting  A University hospital-affiliated research Unit. Patients  The patients were MV patients with injured (n = 5) or normal lungs (n = 6), and spontaneously breathing patients (n = 5). Interventions  None. Measurements and results  Eight image series involving 3, 5, 7, and 10 mm slices and standard and sharp filters were reconstructed from identical CT raw data. Hyperinflated (V _hyper), normally (V _normal), poorly (V _poor), and nonaerated (V _non) volumes were calculated by densitometry as percentage of total lung volume (V _total). V _hyper obtained with the sharp filter systematically exceeded that with the standard filter showing a median (interquartile range) increment of 138 (62–272) ml corresponding to approximately 4% of V _total. In contrast, sharp filtering minimally affected the other subvolumes (V _normal, V _poor, V _non, and V _total). Decreasing slice thickness also increased V _hyper significantly. When changing from 10 to 3 mm thickness, V _hyper increased by a median value of 107 (49–252) ml in parallel with a small and inconsistent increment in V _non of 12 (7–16) ml. Conclusions  Reconstruction parameters significantly affect quantitative CT assessment of V _hyper in MV patients. Our observations suggest that sharp filters are inappropriate for this purpose. Thin slices combined with standard filters and more appropriate thresholds (e.g., −950 HU in normal lungs) might improve the detection of V _hyper. Different studies on V _hyper can only be compared if identical reconstruction parameters were used. This work was supported by institutional sources and in part by funding to Andreas Reske from the German Interdisciplinary Association of Critical Care Medicine.     

Response to hypercapnic challenge is associated with successful weaning from prolonged mechanical ventilation due to brain stem lesions

Objective  We propose that higher airway occlusion pressure (P0.1) responses to hypercapnic challenge (HC) indicate less severe injury. The study aim was to determine whether P0.1 responses to HC were associated with successful weaning after prolonged mechanical ventilation (PMV) in patients with brainstem lesions and to determine a reference value for clinical use. Design and setting  Forty-two patients with brainstem lesions on PMV were recruited. Breathing parameters and P0.1 were measured before HC. Three-minute HC challenges with increasing CO₂ concentrations were initiated and P0.1, respiratory rate, minute ventilation (V _e), tidal volume (V _t) and end tidal CO₂ were measured. Measurements and results  Patients were classified into high (group I) and low (group II) response groups on the basis of P0.1 responses to HC. Increases in V _e and V _t after HC were significantly greater in group I patients (12.22 ± 8.22 vs. 3.08 ± 4.84 L/min, P < 0.001 and 399.11 ± 278.18 vs. 110.54 ± 18.275 ml, P < 0.001). P0.1 levels were significantly higher in group I compared to group II before HC (2.69 ± 1.81 vs. 1.28 ± 1.04 cmH₂O, P = 0.003). The increase in P0.1 following HC was significantly greater in group I compared to group II patients (11.05 ± 4.06 vs. 2.90 ± 2.53 cmH₂O, P < 0.001). Weaning success was significantly higher in group I compared to group II patients (72.2% vs. 33.3%, P = 0.02). A P0.1 increase of >6 cmH₂O following HC was significantly associated with successful weaning. Conclusions  Assessing the P.01 response to serial increases in the level of HC may be a safe means to ascertain whether patients with brainstem lesions are ready for ventilator weaning. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Ultrasound Bio-microscopy for Measurement of Coronary Artery Flow and Estimation of Infarct Size in a Mouse Model of Acute Myocardial Infarction

Ultrasound bio-microscopy was used to measure hemodynamic changes in the left main coronary artery after myocardial infarction (MI), and its usefulness in estimating infarct size was evaluated. MI was induced by left anterior descending artery ligation. Diastolic peak velocity (V_d), mean flow velocity (V_mean) and the velocity-time integral (VTI) were measured 2 and 6 h after MI. Serum troponin I levels were assayed 2, 6 and 12 h after MI. At 2 h, V_mean and VTI significantly differed between mice that underwent low and high left anterior descending artery ligation; V_d, V_mean and VTI were correlated with infarct size (r = −0.557, −0.693 and −0.672, respectively; all p < 0.01). Infarct size was more strongly correlated with 2-h ultrasound bio-microscopy measurements than with 2-h serum troponin I level. Measurement of coronary artery blood flow by ultrasound bio-microscopy may be useful for early estimation of infarct size in mice.     

Baseline perfusion CT parameters as potential biomarkers in predicting long-term prognosis of localized clear cell renal cell carcinoma

Purpose

We aimed to explore the relationship among baseline perfusion CT parameters, clinical, and pathological factors with post-nephrectomy long-term progression-free survival in localized clear cell renal cell carcinoma.

Materials and methods

This study retrospectively collected 127 patients from March 2005 to May 2007 who undertook perfusion CT. 61 patients were confirmed of pT1N0M0 or pT2N0M0 ccRCC. The mean follow-up time is 118.8 months (± 13.1 m, range 72–135 m). We compared clinical, pathological factors (gender, T stage, age, Fuhrmann grade, VEGF level, and MVD), and perfusion parameters before treatment [blood flow (BF), blood volume, mean transition time, and permeability surface-area product] between groups with post-nephrectomy metastasis and without metastasis. Association between covariates and progression-free survival (PFS) were analyzed using Cox proportional regression.

Results

Among 61 patients, 11 developed distant metastasis (10 in the lung, one in the bone). BF in metastatic group [429.1 (233.8, 570.1) ml/min/100 g] was significantly higher than non-metastatic group [214.3 (153.3, 376.5) ml/min/100 g] (p = 0.011). Metastatic group also had more patients with higher Fuhrmann grade. Multi-covariant Cox regression demonstrated T staging, Fuhrmann grade, and BF were significantly associated with PFS [hazard ratio (HR) 3.35, 3.08, and 1.006]. In another model, BF > 230 ml/min/100 g was associated with PFS (HR 12.90), along with T staging and Fuhrmann grade (HR 4.73, 3.69).

Conclusion

Baseline tumor BF is a potential biomarker in prediction long-term metastasis of localized ccRCC and may help screening for higher risk localized ccRCC patients who need personalized surveillance strategy after nephrectomy.

     

Respiratory,metabolic and hemodynamic effects of clonidine in ventilated patients presenting with withdrawal syndrome

Objective  To investigate the respiratory, metabolic and hemodynamic effects of clonidine in ventilated patients presenting with withdrawal syndrome after sedation interruption. Design  Prospective, interventional, single-center study in 30 ventilated ICU patients. Interventions  Metabolic [oxygen consumption (VO₂), CO₂ production (VCO₂), resting energy expenditure (REE)], respiratory [minute ventilation (V _E), tidal volume (V _T), respiratory rate (RR)] and hemodynamic (HR, SAP, MAP) parameters were measured in 30 ventilated ICU patients. Measurements were performed first under sedation with remifentanil–propofol, then after sedation interruption, and finally after clonidine administration (0.9–1.8 mg of clonidine in two doses of 10 min interval). Results  Sedation interruption produced significant increases in the hemodynamic parameters (SAP and MAP by 33%, HR by 37%), and metabolic rate (increase in VO₂ by 70%, VCO₂ by 88% and REE by 74%), leading to high respiratory demands (increase in V _E from 9 to 15 l/min). The V _E was increased due to a twofold increase in the RR; V _T remained constant. In 25 out of 30 patients, clonidine administration decreased the hemodynamic (SAP, MAP and HR), metabolic (VO₂, VCO₂, REE) and respiratory parameters to values close to those observed with sedation. Clonidine induced mild sedation and patients became more cooperative with the ventilator. All patients responding to clonidine were weaned from the ventilator in 2 days (median, range 1–18 days). Conclusion  Patients with withdrawal syndrome had significantly elevated hemodynamic, metabolic and respiratory demands. Clonidine significantly decreased these demands, induced mild sedation and facilitated patient cooperation with the ventilator, enabling ventilator weaning. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comparison of different methods for dead space measurements in ventilated newborns using CO2-volume plot

Objective: The aim of the study was to test the applicability of Ventrak 1550/Capnogard 1265 (V-C) for respiratory dead space (Vd) measurement and to determine anatomic (V_Dana), physiologic (V_Dphys), and alveolar dead spaces (V_Dalv) in ventilated neonates. Design: Prospective study. Setting: Neonatal intensive care unit. Patients: 33 investigations in 22 ventilated neonates; median gestational age 34.5 weeks (range 27–41), median birthweight 2658 g (range 790–3940). Method: The single-breath CO₂ test (SBT-CO₂) and transcutaneous partial pressure of carbon dioxide (PCO₂) were recorded simultaneously and Vd was determined (1) automatically (V-C software), (2) by interactive analysis of the PCO₂ volume plot, and (3) manually by Bohr/Enghoff equations using data obtained by V-C. Results: Vd measurements were possible in all cases by method 3 but not possible by methods 1 and 2 in 22 of 33 investigations (67 %), especially in preterm neonates, because of disturbed signals. V_Dana/kg (1.6 ± 0.6 ml/kg, mean ± SD), V_Dana/tidal volume (Vt) (0.36 ± 0.09) were lower compared to published data in spontaneously breathing infants, whereas V_Dphys/kg (2.3 ± 0.9 ml/kg) and V_Dphys/Vt (0.50 ± 0.12) are comparable to data obtained from the literature. Five minutes after insertion of the sensor (dead space 2.6 ml) into the ventilatory circuit, the transcutaneous PCO₂ rose above baseline for 3.2 % (patients > 2500 g) and 5.7 % (patients < 2500 g). The time necessary for one analysis was 50–60 min. Conclusion: In ventilated newborns, dead space measurements were possible only in one-third by SBT-CO₂, but in all cases by Bohr/Enghoff equations. Improved software could further reduce the time needed for one analysis. Received: 8 December 1998 Accepted: 19 April 1999     

Pharmacokinetics and absolute bioavailability of phenobarbital in neonates and young infants,a population pharmacokinetic modelling approach

Phenobarbital is widely used for treatment of neonatal seizures. Its optimal use in neonates and young infants requires information regarding pharmacokinetics. The objective of this study is to characterize the absolute bioavailability of phenobarbital in neonates and young infants, a pharmacokinetic parameter which has not yet been investigated. Routine clinical pharmacokinetic data were retrospectively collected from 48 neonates and infants (weight: 0.7–10 kg; patient's postnatal age: 0–206 days; GA: 27–42 weeks) treated with phenobarbital, who were administered as intravenous or suspension by oral routes and hospitalized in a paediatric intensive care unit. Total mean dose of 4.6 mg/kg (3.1–10.6 mg/kg) per day was administered by 30‐min infusion or by oral route. Pharmacokinetic analysis was performed using a nonlinear mixed‐effect population model software). Data were modelled with an allometric pharmacokinetic model, using three‐fourths scaling exponent for clearance (CL). The population typical mean [per cent relative standard error (%RSE)] values for CL, apparent volume of distribution (V_d) and bioavailability (F) were 0.0054 L/H/kg (7%), 0.64 L/kg (15%) and 48.9% (22%), respectively. The interindividual variability of CL, V_d, F (%RSE) and residual variability (%RSE) was 17% (31%), 50% (27%), 39% (27%) and 7.2 mg/L (29%), respectively. The absolute bioavailability of phenobarbital in neonates and infants was estimated. The dose should be increased when switching from intravenous to oral administration.     

Usefulness of CT volumetry for primary gastric lesions in predicting pathologic response to neoadjuvant chemotherapy in advanced gastric cancer

Background  To investigate the utility of CT volumetry for primary gastric lesions in the prediction of pathologic response to neoadjuvant chemotherapy in patients with resectable advanced gastric cancer (AGC). Materials and methods  Thirty-three consecutive patients with resectable AGC stage ≥T2 and N1), who had been treated with neoadjuvant chemotherapy and radical gastric resection, were prospectively enrolled in this study. There were 30 men and 3 women with a mean age of 53.8 years. Contrast-enhanced CT was obtained after gastric distention with air before and after chemotherapy using a MDCT scanner. Pre- and post-chemotherapy thickness or short diameter and volume of the primary gastric tumor and largest lymph node (LN), were measured using a dedicated 3D software by two radiologists in consensus. PET/CT was also performed and the peak standardized uptake value (SUV) of primary gastric tumor and largest LN before and after chemotherapy was measured. The percentage diameter, volume, and SUV reduction rates for both the primary gastric tumor and the LN, were calculated and correlated with the histopathologic grades of regression using the Spearman correlation test. Differentiation between pathologic responders and nonresponders was assessed using receiver operating characteristic (ROC) analysis. Results  Among the three CT parameters which showed significant correlation with the histopathologic grades of regression, the correlation factor was highest in the percentage volume reduction rate of primary gastric tumor (ρ = 0.484, P = 0.004) followed by percentage volume reduction of the index node (ρ = 0.397, P = 0.022), and percentage diameter reduction of the index node (ρ = 0.359, P = 0.04). However, the percentage thickness decrease rate (P = 0.208) and the percentage SUV reduction rate (P = 0.619) of primary gastric tumor were not significantly correlated with the histopathologic grades of regression. When the optimal cutoff value of the percentage volume reduction rate of primary gastric tumor was determined to be 35.6%, a sensitivity of 100% (16/16) and a specificity of 58.8% (10/17) were achieved. Conclusion  CT volumetry for primary gastric tumor may be the most accurate tool in the prediction of pathologic response following neoadjuvant chemotherapy in patients with resectable AGC.     

动态增强MRI定量评估乳腺良恶性病变的效能

目的 探讨动态增强磁共振成像（DCE-MRI）评价乳腺良恶性病变中病灶及背景实质血流动力学参数的价值。方法 收集41例接受乳腺DCE-MRI检查的患者（共45个病灶）,其中良性病变21个（良性组）,恶性病变24个（恶性组）,测量病灶及背景实质的容量转移常数（K_trans）、速率常数（K_ep）、血浆分数（V_p）,对2组各参数进行统计学分析;以病理结果为金标准,评价各参数诊断乳腺恶性病灶的效能。结果 恶性组病灶K_trans和K_ep、背景实质K_trans和K_ep均高于良性组（P均<0.05）。2组病灶V_p和背景实质V_p差异均无统计学意义（P均>0.05）。诊断乳腺恶性病变时,背景实质K_trans的AUC较其他参数高,敏感度、特异度分别为87.50%、76.19%。所有参数联合的Logistic回归模型AUC值最高,为0.86（P<0.001）。结论 DCE-MRI相关参数中,背景实质K_trans对乳腺疾病的诊断价值较高。定量分析DCE-MRI数据有助于鉴别乳腺良恶性病变,其背景实质的血流动力学特征有望成为无创诊断乳腺病变的新方法。     

Antioxidant status and lipid peroxidation in the blood of breast cancer patients of different ages after chemotherapy with 5-fluorouracil,doxorubicin and cyclophosphamide

ObjectivesBreast carcinoma is related to the increase of lipid peroxidation in plasma with concomitant decrease of antioxidant (AO) defense capacity in blood cells, which becomes more pronounced during aging of the patients. This work evaluated the potential age-related effect of chemotherapy with 5-fluorouracil, doxorubicin and cyclophosphamide (FAC) on the level of lipid hydroperoxides (LP), glutathione (GSH), AO enzyme activities of copper, zinc superoxide dismutase (CuZnSOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) in breast cancer patients. The level of CuZnSOD protein was assessed after the FAC therapy and radiotherapy of breast cancer.Design and methodsAO parameters were measured in the blood of 58 breast cancer patients and 60 healthy age-matched healthy subjects by biochemical and Western blot analyses.ResultsIncreased oxidative stress (LP: p < 0.05) and decreased AO enzyme activities (CuZnSOD: p < 0.01, GPx: p < 0.05, GR: p < 0.01) and GSH level (p < 0.01) in the blood of breast cancer patients in response to FAC chemotherapy seem not to be age-dependent. CuZnSOD enzyme expression decreased after the FAC chemotherapy (p < 0.05), while it increased after the radiotherapy of breast cancer (p < 0.05).ConclusionFAC chemotherapy and radiotherapy promote further oxidative shift, which potentiate already existing chronic oxidative stress linked to breast cancer. In these effects, impaired capacity for H₂O₂ detoxification (CAT, GPX and GSH) seems to have major contribution.     

Pharmacokinetics of Ketamine at Dissociative Doses in an Adult Patient With Refractory Status Asthmaticus Receiving Extracorporeal Membrane Oxygenation Therapy

PurposeFirst-line management of severe asthma exacerbations include the use of inhaled short-acting β-agonists, anticholinergics, and systemic corticosteroids. Continuous intravenous ketamine given at dissociative doses may be a pharmacologic option in patients who are intubated with life-threatening severe bronchospasm unresponsive to standard therapy. We describe the case of a 44-year-old man admitted to the intensive care unit for status asthmaticus requiring intubation and mechanical ventilation.MethodsThe patient developed severe refractory hypercapnic respiratory failure necessitating additional respiratory support with veno-venous extracorporeal membrane oxygenation (ECMO) therapy. Ketamine treatment was initiated at 0.5 mg/kg/h continuous infusion on the day of admission for pain control and required up-titration to 2 mg/kg/h by intensive care unit day 4 for bronchodilation. Whole blood samples were obtained for pharmacokinetic analysis of ketamine during ECMO.FindingsThe plasma concentration at steady state was 1018.7 ng/mL, with an estimated clearance of 1.96 L/kg/h after up-titration. The V_d was 14.18 L/kg, the k_e was 0.14 hr⁻¹, and the t_½ was 5 hours.ImplicationsCompared with healthy adults, there was a 6.5-fold increase in the V_d. However, the V_d was similar compared with critically ill patients not receiving ECMO. Further studies should focus on the effect of ECMO on ketamine pharmacokinetic properties.     

Usefulness of 3′-[F-18]Fluoro-3′-deoxythymidine with Positron Emission Tomography in Predicting Breast Cancer Response to Therapy

Objective The usefulness of 2-deoxy-2-[F-18]fluoro-d-glucose (FDG)–positron emission tomography (PET) in monitoring breast cancer response to chemotherapy has previously been reported. Elevated uptake of FDG by treated tumors can persist however, particularly in the early period after treatment is initiated. 3′-[F-18]Fluoro-3′-deoxythymidine (FLT) has been developed as a marker for cellular proliferation and, in principle, could be a more accurate predictor of the long-term effect of chemotherapy on tumor viability. We examined side-by-side FDG and FLT imaging for monitoring and predicting tumor response to chemotherapy. Methods Fourteen patients with newly diagnosed primary or metastatic breast cancer, who were about to commence a new pharmacologic treatment regimen, were prospectively studied. Dynamic 3-D PET imaging of uptake into a field of view centered over tumor began immediately after administration of FDG or FLT (150 MBq). After 45 minutes of dynamic acquisition, a clinically standard whole-body PET scan was acquired. Patients were scanned with both tracers on two separate days within one week of each other (1) before beginning treatment, (2) two weeks following the end of the first cycle of the new regimen, and (3) following the final cycle of that regimen, or one year after the initial PET scans, whichever came first. (Median and mean times of early scans were 5.0 and 6.6 weeks after treatment initiation; median and mean times for late scans were 26.0 and 30.6 weeks after treatment initiation.) Scan data were analyzed on both tumor-by-tumor and patient-by-patient bases, and compared to each patient's clinical course. Results Mean change in FLT uptake in primary and metastatic tumors after the first course of chemotherapy showed a significant correlation with late (av. interval 5.8 months) changes in CA27.29 tumor marker levels (r = 0.79, P = 0.001). When comparing changes in tracer uptake after one chemotherapy course versus late changes in tumor size as measured by CT scans, FLT was again a good predictor of eventual tumor response (r = 0.74, P = 0.01). Tumor uptake of FLT was near-maximal by 10 minutes after injection. The time frame five to 10 minutes postinjection of FLT produced standardized uptake value (SUV) values highly correlated with SUV values obtained after 45-minute uptake (r = 0.83, P < 0.0001), and changes in these early SUVs after the first course of chemotherapy correlated with late changes in CA27.29 (r = 0.93, P = 0.003). Conclusion A 10-minute FLT-PET scan acquired two weeks after the end of the first course of chemotherapy is useful for predicting longer-term efficacy of chemotherapy regimens for women with breast cancer.     

Effect of tidal volume in children with acute hypoxemic respiratory failure

Objectives  To determine if tidal volume (V _T) between 6 and 10 ml/kg body weight using pressure control ventilation affects outcome for children with acute hypoxemic respiratory failure (AHRF) or acute lung injury (ALI). To validate lung injury severity markers such as oxygenation index (OI), PaO₂/FiO₂ (PF) ratio, and lung injury score (LIS). Design  Retrospective, January 2000–July 2007. Setting  Tertiary care, 20-bed PICU. Patients  Three hundred and ninety-eight endotracheally intubated and mechanically ventilated children with PF ratio <300. Outcomes were mortality and 28-day ventilator free days. Measurements and main results  Three hundred and ninety-eight children met study criteria, with 20% mortality. 192 children had ALI. Using >90% pressure control ventilation, 85% of patients achieved V _T less than 10 ml/kg. Median V _T was not significantly different between survivors and non-survivors during the first 3 days of mechanical ventilation. After controlling for diagnostic category, age, delta P (PIP-PEEP), PEEP, and severity of lung disease, V _T was not associated with mortality (P > 0.1), but higher V _T at baseline and on day 1 of mechanical ventilation was associated with more ventilator free days (P < 0.05). This was particularly seen in patients with better respiratory system compliance [Crs > 0.5 ml/cmH₂0/kg, OR = 0.70 (0.52, 0.95)]. OI, PF ratio, and LIS were all associated with mortality (P < 0.05). Conclusions  When ventilating children using lung protective strategies with pressure control ventilation, observed V _T is between 6 and 10 ml/kg and is not associated with increased mortality. Moreover, higher V _T within this range is associated with more ventilator free days, particularly for patients with less severe disease. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

The effect of neuromuscular blockade on oxygen consumption in sedated and mechanically ventilated pediatric patients after cardiac surgery

Objective  To measure the effect of intense neuromuscular blockade (NMB) on oxygen consumption (VO₂) in deeply sedated and mechanically ventilated children on the first day after complex congenital cardiac surgery. Design  Prospective clinical interventional study. Setting  Pediatric intensive care unit of an university medical centre. Measurements and results  Nine mechanically ventilated and sedated children (weight 2.8–8.7 kg) were included. All children were treated with vasoactive drugs. The level of sedation was quantified using the comfort score, Ramsay score and bispectral index (BIS). The intensity of NMB was quantified using acceleromyography and VO₂ was measured using indirect calorimetry. Analgo-sedation using various intravenous agents was targeted at a deep level (comfort score < 18, BIS < 60 and Ramsay score > 4). NMB was achieved by intravenous administration of rocuronium. All measurements were conducted before, during and after recovery from a period of intense NMB. Baseline values were VO₂ 6.1 ml/(kg min) (SD 1.3), comfort score 13 (SD 0.7), BIS 42.5 (SD 14.2), mean blood pressure 54.0 mmHg (SD 10.5), mean heart rate 129.9 bpm (SD 28.9) and mean core temperature 36.7°C (SD 0.5). There were no significant differences in VO₂ or other parameters between baseline, during NMB and the recovery phase. Conclusion  Neuromuscular blocking agents do not reduce oxygen consumption in deeply sedated and mechanically ventilated children after congenital cardiac surgery.