A new formula for determining arterial oxygen saturation during venovenous extracorporeal oxygenation

Purpose

Venovenous extracorporeal membrane oxygenation (VV-ECMO) is used to treat severe forms of acute respiratory distress syndrome (ARDS). VV-ECMO management may be confusing due to the lack of information about the interplay between the determinant parameters and their impact on oxygenation. We found a relationship between arterial oxygen saturation (SaO₂) and its relevant parameters. The aim of this study was to assess the validity of this model.

Methods

We report our experience in 17 patients under VV-ECMO for severe ARDS. We compared, at two different levels of pump flow, SaO₂ and the oxygen saturation measured in the pulmonary artery (SpaO₂) with the predicted saturation using the formula: SpaO₂ = (EF/CO)SmO₂ + (1 ? EF/CO)SvO₂ + 10^?2PmO₂, where PF is pump flow, R is recirculation, EF is effective flow [= (1 ? R)PF], SmO₂ is saturation of the oxygenator outgoing blood, CO is cardiac output, SvO₂ is saturation of mixed venous blood, and PmO₂ is oxygen partial pressure of the oxygenator outgoing blood.

Results

There was no significant difference between predicted and measured SpaO₂: the mean predicted and measured SpaO₂ values were 90.7 ± 2.8 % and 90.4 ± 2.7 % , respectively (p = 0.696, r = 0.966). Bland-Altman analysis showed good agreement between predicted and measured SpaO₂. Predicted SpaO₂ and SaO₂ was well correlated (r = 0.80).

Conclusions

We have presented an explicit relationship between SaO₂ and its direct determinants during VV-ECMO. Good agreement was found with the measured values of SaO₂, but the model remains to be fully validated before its use in clinical practice.     

The influence of age and BMI on intervertebral disc height and oropharyngeal airway in Japanese men and women

Objective

Intervetebral disc height changes with both age and increasing body mass index (BMI), known risk factors for obstructive sleep apnea (OSA). We studied the relationship of body mass index (BMI) and aging in the neck structures to disc compression and oropharyngeal airway size and shape.

Materials and methods

The intervertebral disc (IVD), neck and airway volumes were measured at the C2 level only from Computerized Tomography scans using a semi-automatic segmentation tool. The change of intervertebral disc height/volume with age and BMI were examined in 38 consecutive Japanese patients (Male: 19, Female: 19), group matched for age (men: 52.2 ± 15.36 years; women: 52.4 ± 17.37) and BMI (men: 23.1 ± 2.97 m/kg²; women: 21.6 ± 4.03 m/kg²).

Results

In this study, the intervertebral disc volume as a percent of neck volume was larger in men than in women (P = 0.039), and the intervertebral disc volume (r = ?0.588; P = 0.013) and height (r = ?0.510; P = 0.037) decreased with increasing age-adjusted BMI in males only. Age was not significantly correlated with any of the volumes. The intervertebral airway volume significantly decreased with increasing age-adjusted BMI in our female subjects (r = ?0.588; P = 0.013).

Conclusion

In our Japanese volunteer population, the intervertebral disc is compressed vertically with the increase of BMI in males only, and the oropharyngeal airway volume decreases with increasing BMI in females only. These results may be useful in assessment of OSA risk.     

Early CPAP prevents evolution of acute lung injury in patients with hematologic malignancy

Purpose

Although chemotherapy and transplantation improve outcome of patients with hematological malignancy, complications of these therapies are responsible for a 20–50% mortality rate that increases when respiratory symptoms evolve into acute lung injury (ALI). The aim of this study is to determine the effectiveness of early continuous positive airway pressure (CPAP) delivered in the ward to prevent occurrence of ALI requiring intensive care unit (ICU) admission for mechanical ventilation.

Methods

Patients with hematological malignancy presenting in the hematological ward with early changes in respiratory variables were randomized to receive oxygen (N = 20) or oxygen plus CPAP (N = 20). Primary outcome variables were need of mechanical ventilation requiring ICU admission, and intubation rate among those patients who required ICU admission.

Results

At randomization, arterial-to-inspiratory O₂ ratio in control and CPAP group was 282 ± 41 and 256 ± 52, respectively. Patients who received CPAP had less need of ICU admission for mechanical ventilation (4 versus 16 patients; P = 0.0002). CPAP reduced the relative risk for developing need of ventilatory support to 0.25 (95% confidence interval: 0.10–0.62). Among patients admitted to ICU, intubation rate was lower in the CPAP than in the control group (2 versus 14 patients; P = 0.0001). CPAP reduced the relative risk for intubation to 0.46 (95% confidence interval: 0.27–0.78).

Conclusions

This study suggests that early use of CPAP on the hematological ward in patients with early changes in respiratory variables prevents evolution to acute lung injury requiring mechanical ventilation and ICU admission.     

Dobutamine reverses the vasopressin-associated impairment in cardiac index and systemic oxygen supply in ovine endotoxemia

Introduction

Arginine vasopressin (AVP) is increasingly used to treat sepsis-related vasodilation and to decrease catecholamine requirements. However, AVP infusion may be associated with a marked decrease in systemic blood flow and oxygen transport. The purpose of the present study was to evaluate whether dobutamine may be titrated to reverse the AVP-related decrease in cardiac index (CI) and systemic oxygen delivery index (DO₂I) in an established model of ovine endotoxemia.

Methods

Twenty-four adult ewes were chronically instrumented to determine cardiopulmonary hemodynamics and global oxygen transport. All ewes received a continuous endotoxin infusion that contributed to a hypotensive-hyperdynamic circulation and death of five sheep. After 16 hours of endotoxemia, the surviving ewes (n = 19; weight 35.6 ± 1.5 kg (mean ± SEM)) were randomized to receive either AVP (0.04 Umin^-1) and dobutamine (n = 8) or the vehicle (normal saline; n = 6) and compared with a third group treated with AVP infusion alone (n = 5). Dobutamine infusion was started at an initial rate of 2 μg kg^-1min^-1 and was increased to 5 and 10 μg kg^-1 min^-1 after 30 and 60 minutes, respectively.

Results

AVP infusion increased mean arterial pressure (MAP) and systemic vascular resistance index at the expense of a markedly decreased CI (4.1 ± 0.5 versus 8.2 ± 0.3 l min^-1 m^-2), DO₂I (577 ± 68 versus 1,150 ± 50 ml min^-1 m^-2) and mixed-venous oxygen saturation (S_vO₂; 54.5 ± 1.8% versus 69.4 ± 1.0%; all p < 0.001 versus control). Dobutamine dose-dependently reversed the decrease in CI (8.8 ± 0.7 l min^-1 m^-2 versus 4.4 ± 0.5 l min^-1 m^-2), DO₂I (1323 ± 102 versus 633 ± 61 ml min^-1 m^-2) and S_vO₂ (72.2 ± 1.7% versus 56.5 ± 2.0%, all p < 0.001 at dobutamine 10 μg kg^-1 min^-1 versus AVP group) and further increased MAP.

Conclusion

This study provides evidence that dobutamine is a useful agent for reversing the AVP-associated impairment in systemic blood flow and global oxygen transport.     

Validation of four prognostic scores in patients with cancer admitted to Brazilian intensive care units: results from a prospective multicenter study

Objective

The aim of the present study was to validate the Simplified Acute Physiology Score II (SAPS II) and 3 (SAPS 3), the Mortality Probability Models III (MPM₀-III), and the Cancer Mortality Model (CMM) in patients with cancer admitted to several intensive care units (ICU).

Design

Prospective multicenter cohort study.

Setting

Twenty-eight ICUs in Brazil.

Patients

Seven hundred and seventeen consecutive patients (solid tumors 93%; hematological malignancies 7%) included over a 2-month period.

Interventions

None.

Measurements and main results

Discrimination was assessed by area under receiver operating characteristic (AROC) curves and calibration by Hosmer–Lemeshow goodness-of-fit test. The main reasons for ICU admission were postoperative care (57%), sepsis (15%) and respiratory failure (10%). The ICU and hospital mortality rates were 21 and 30%, respectively. When all 717 patients were evaluated, discrimination was superior for both SAPS II (AROC = 0.84) and SAPS 3 (AROC = 0.84) scores compared to CMM (AROC = 0.79) and MPM₀-III (AROC = 0.71) scores (P < 0.05 in all comparisons). Calibration was better using CMM and the customized equation of SAPS 3 score for South American countries (CSA). MPM₀-III, SAPS II and standard SAPS 3 scores underestimated mortality (standardized mortality ratio, SMR > 1), while CMM tended to overestimation (SMR = 0.48). However, using the SAPS 3 for CSA resulted in more precise estimations of the probability of death [SMR = 1.02 (95% confidence interval = 0.87–1.19)]. Similar results were observed when scheduled surgical patients were excluded.

Conclusions

In this multicenter study, the customized equation of SAPS 3 score for CSA was found to be accurate in predicting outcomes in cancer patients requiring ICU admission.     

Percutaneous implantation of the Edwards SAPIEN™ pulmonic valve: initial results in the first 22 patients

Background

Percutaneous pulmonary valve implantation (PPVI) was introduced in 2000 as an interventional procedure for the treatment of right ventricular outflow tract (RVOT) dysfunction. The new Edwards SAPIEN^? pulmonic valve has reached CE certification at the end of 2010 thus offering an attractive alternative with extended sizes (23 and 26 mm) to the conventional Melody^® valve (sizes 18, 20 and 22 mm).

Patients

Over a 1-year period, PPVI using the Edwards SAPIEN^? pulmonic valve was performed in 22 patients using a standardized procedure. Primary diagnosis was tetralogy of Fallot (n = 11), pulmonary atresia (n = 2), Truncus arteriosus (n = 3), TGA/PS-Rastelli (n = 1), Ross surgery (n = 2), double outlet right ventricle (n = 2) and absent pulmonary valve syndrome (n = 1). The character of the RVOT for PPVI was transannular patch (n = 4), bioprosthesis (n = 2), homograft (n = 5) and Contegra^® conduit (n = 11). The leading hemodynamic problem consisted of a pulmonary stenosis (PS) (n = 2), pulmonary regurgitation (PR) (n = 11) and a combined PS/PR lesion (n = 9).

Results

In 21/22 patients, PPVI was performed successfully (10 × 23 and 11 × 26 mm). There were 9 female and 13 male patients; the mean age was 21.7 years (range 6–83 years), the mean length was 162 cm (range 111–181 cm) and the weight 56.5 kg (range 20–91 kg). Invasive data showed a decrease of RV-systolic pressure from 61.2 mmHg (±23.1) to 41.2 mmHg (±8.6) and reduction of RV–PA gradient from 37.3 mmHg (±23.2) to 6.9 mmHg (±5.3). The PA-systolic pressure increased from 25.8 mmHg (±8.6) to 33.9 mmHg (±9.3) as did the PA diastolic pressure (from 6.0 mmHg (±5.6) to 14.6 mmHg (±4.3). There was a substantial reduction of pulmonary regurgitation from before (none/trivial n = 0, mild n = 2, mode rate n = 9, severe n = 11) to after PPVI (none/trivial n = 20, mild n = 1). During the short-term follow-up of 5.7 months there was no change in the immediate results.

Conclusion

PPVI using the Edwards SAPIEN^? pulmonic valve can be performed safely in a wide range of patients with various diagnoses and underlying pathology of the RVOT and enables the restoration of an adult-size RVOT diameter. Although the immediate and short-term results seem promising, the long-term effects and safety have to be assessed in further clinical follow-up studies.     

Evolution of haemodynamics and outcome of fluid-refractory septic shock in children

Background

Maintaining threshold values of cardiac output (CO) and systemic vascular resistance (SVR) when used as part of the American College of Critical Care Medicine (ACCM) haemodynamic protocol improves the outcomes in paediatric septic shock.

Objective

We observed the evolution of CO and SVR during the intensive care admission of children with fluid-refractory septic shock and report this together with the eventual outcomes.

Design

Prospective observational study.

Setting

Tertiary care Paediatric Intensive Care Unit (PICU) in London.

Methods

Children admitted in fluid refractory septic shock to the Intensive Care Unit over a period of 36 months were studied. Post liver re-transplant children and delayed septic shock admissions were excluded. A non-invasive ultrasound cardiac output monitor device (USCOM) was used to measure serial haemodynamics. Children were allocated at presentation into one of two categories: (1) hospital-acquired infection and (2) community-acquired infection. Vasopressor, inotrope or inodilator therapies were titrated to maintain threshold cardiovascular parameters as per the ACCM guidelines.

Results

Thirty-six children [19 male, mean age (SD) 6.78 (5.86) years] were admitted with fluid-refractory septic shock and studied. At presentation, all 18 children with hospital-acquired (HA) sepsis and 3 from among the community-acquired (CA) sepsis group were in ‘warm shock’ (SVRI < 800 dyne s/cm⁵/m²) whereas 15 of the 18 children with community-acquired sepsis and none in the hospital-acquired group were in ‘cold shock’ [cardiac index (CI) < 3.3 l/min/m²]. All 21 children in ‘warm shock’ were initially commenced on a vasopressor (noradrenaline). Despite an initial good response, four patients developed low CI and needed adrenaline. Similarly, all 15 children in cold shock were initially commenced on adrenaline. However, two of them subsequently required noradrenaline. Five others needed milrinone as an inodilator. In general, both groups of children had normalised SVRI and CI within 42 h of therapy but required variable doses of vasopressors, inotropes or inodilators in a heterogeneous manner. The overall 28-day survival rate was 88.9 % in both groups. Central venous oxygen saturation (ScvO2) was significantly (p = 0.003) lower in the community-acquired group (mean 51.72 % ± 4.26) when compared to the hospital-acquired group (mean 58.72 % ± 1.36) at presentation but showed steady improvement during therapy. Gram-positive organisms were predominant in blood cultures, 61 % in HA and 56 % in CA groups.

Conclusions

In general, we found children with community-acquired septic shock presented in cold shock whereas hospital-acquired septic shock children manifested warm shock. Both types evolved in a heterogeneous manner needing frequent revision of cardiovascular support therapy. However the 28-day survival in both groups was the same at 89 %. Frequent measurements of haemodynamics using non-invasive ultrasound helped in fine tuning cardiovascular therapies.     

Reproducibility of Static and Dynamic 18F-FDG, 18F-FLT, and 18F-FMISO MicroPET Studies in a Murine Model of HER2+ Breast Cancer

Purpose

The objective of this study is to determine the reproducibility of static 2-deoxy-2-[¹⁸F]fluoro-D-glucose (¹⁸F-FDG), 3′-deoxy-3′-[¹⁸F]fluorothymidine (¹⁸F-FLT), and [¹⁸F]-fluoromisonidazole (¹⁸F-FMISO) microPET measurements, as well as kinetic parameters returned from analyses of dynamic ¹⁸F-FLT and ¹⁸F-FMISO data.

Procedures

HER2+ xenografts were established in nude mice. Dynamic data were acquired for 60 min, followed by a repeat injection and second scan 6 h later. Reproducibility was assessed for the percent-injected dose per gram (%ID/g) for each radiotracer, and with kinetic parameters (K ₁ –k ₄ , K _i ) for ¹⁸F-FLT and ¹⁸F-FMISO.

Results

The value needed to reflect a change in tumor physiology is given by the 95 % confidence interval (CI), which is ±14, ±5, and ±6 % for ¹⁸F-FDG (n?=?12), ¹⁸F-FLT (n?=?11), and ¹⁸F-FMISO (n?=?11) %ID/g, respectively. V _d (=K ₁ /k ₂), k ₃, and K _FLT are the most reproducible ¹⁸F-FLT (n?=?9) kinetic parameters, with 95 % CIs of ±18, ±10, and ±18 %, respectively. V _d and K _FMISO are the most reproducible ¹⁸F-FMISO kinetic parameters (n?=?7) with 95 % CIs of ±16 and ±14 %, respectively.

Conclusions

Percent-injected dose per gram measurements are reproducible and appropriate for detecting treatment-induced changes. Kinetic parameters have larger threshold values, but are potentially sufficiently reproducible to detect treatment response.     

Autoimmune pancreatitis: whole-body 18F-FDG PET/CT findings

Purpose

The study aimed to investigate the function of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT) in diagnosing of autoimmune pancreatitis (AIP) and whole-body evaluation.

Methods

Seven AIP patients who underwent ¹⁸F-FDG PET/CT systemic examination in our hospital from August 2010 to March 2012 were analyzed retrospectively. Systemic PET/CT routine scanning and pancreatic delayed scanning were performed in all patients.

Results

The mean age of 7 AIP patients (6 male and 1 female) was 54.2 years (range from 42 to 71 years). The pancreas showed diffuse enlargement in 6 cases, and segmental enlargement in 1 case. Fluorodeoxyglucose (FDG) uptake was increased in diseased region. The maximum standardized uptake value (SUVmax) was 4.38 ± 0.90 and increased to 5.31 ± 1.08 after delayed scanning, of which small amounts of inflammatory exudate around pancreas was observed in 4 cases. Extrapancreatic lesions (EPLs) were observed in all 7 cases: lymphadenectasis (n = 5), lymphadenectasis with increased FDG uptake (n = 4); associated sialosis with metabolism enlargement (n = 4); associated cholangitis (n = 4); associated interstitial pneumonia (n = 3); inverted “V” shaped high FDG uptake foci in prostate (n = 5).

Conclusions

AIP is a systemic disease. ¹⁸F-FDG PET/CT can exhibit the characteristics of AIP pancreatic lesions, and also better reflect the changes and metabolic characteristics of extrapancreatic organs. It plays a distinct role in diagnosis, differentiating of AIP and whole-body evaluation.     

Automated sedation outperforms manual administration of propofol and remifentanil in critically ill patients with deep sedation: a randomized phase II trial

Purpose

To compare automated administration of propofol and remifentanil guided by the Bispectral index (BIS) versus manual administration of short-acting drugs in critical care patients requiring deep sedation. The primary outcome was the percentage of BIS values between 40 and 60 (BIS_40–60).

Methods

This randomized controlled phase II trial in the intensive care unit (ICU) was conducted in adults with multiorgan failure. Thirty-one patients were assigned to receive sedation with propofol or remifentanil either by an automated or a manual system, both targeting BIS_40–60. Performance and feasibility of an automated administration were assessed.

Results

The study groups were well balanced in terms of demographic characteristics. Study duration averaged 18 [8–24] h in the automated group and 14 [9–21] h in the manual group (p = 0.81). Adequate sedation (BIS_40–60) was significantly more frequent in the automated group 77 [59–82] % than in the manual group 36 [22–56] %, with p = 0.001. Propofol consumption was reduced by a factor of 2 in the automated group with a median change of infusion rates of 39 ± 9 times per hour. In contrast, there were only 2 ± 1 propofol and 1 ± 1 remifentanil dose changes per hour in the manual group compared to 40 ± 9 for remifentanil in the automated group (p < 0.001). Vasopressors were more often discontinued or reduced in the automated group than in the manual control group (36 [6–40] vs. 12 [4–20] modifications, p = 0.03).

Conclusions

Continuous titration of propofol and remifentanil sedation with an automatic controller maintains deep sedation better than manual control in severely ill patients. It is associated with reduced sedative and vasopressor use.     

Prevalence of different forms of infarct-atypical late gadolinium enhancement in patients early and late after heart transplantation

Background

Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) enables high-resolution myocardial tissue characterization, showing the results of different injuries, especially in the early period after heart transplantation (HTX).

Objectives

We sought to apply LGE-CMR to investigate the prevalence and patterns of infarct-atypical myocardial involvement and associated mechanisms in patients early and late after HTX.

Methods

LGE-CMR was performed on a 1.5-T MRI scanner (Philips, Best, the Netherlands) in 89 patients: group 1 (48 patients) less than 2.5 years after operation (1.2 ± 0.5 years) and group 2 (41 patients) later this period (8.2 ± 4.2 years). Following LGE-CMR, the presence, distribution, patterns of infarct-atypical LGE and possible associated mechanisms were assessed.

Results

71 % of group 1 patients (34/48) showed infarct-atypical LGE whereas 57 % of group 2 patients (22/41) were affected (p = 0.25). Fewer segments/patients were involved later after HTX (1.6 ± 2.0 vs. 2.9 ± 3.1 segments/patient; p = 0.03), but only diffuse LGE-CMR pattern decreased significantly (11.5 % of affected segments in group 1 vs. 6.5 % in group 2; p < 0.001). Group 2 had lower ischemic time (181 ± 53 vs. 208 ± 61 min; p = 0.03), the donors were younger (33 ± 13 vs. 41 ± 13 years; p = 0.01) and fewer donors were Toxoplasma gondii seropositive (4 vs. 22pts; p < 0.001).

Conclusion

Infarct-atypical LGE was found in a significant number of patients early post-HTX, however, fewer patients and myocardial segments per patient were affected later after HTX. Many potential factors seem to be involved, but the exact mechanisms are still unclear. Future studies are necessary to test prognostic implications associated with LGE-CMR patterns.     

Effects of dobutamine on systemic, regional and microcirculatory perfusion parameters in septic shock: a randomized, placebo-controlled, double-blind, crossover study

Purpose

The role of dobutamine during septic shock resuscitation is still controversial since most clinical studies have been uncontrolled and no physiological study has unequivocally demonstrated a beneficial effect on tissue perfusion. Our objective was to determine the potential benefits of dobutamine on hemodynamic, metabolic, peripheral, hepatosplanchnic and microcirculatory perfusion parameters during early septic shock resuscitation.

Methods

We designed a randomized, controlled, double-blind, crossover study comparing the effects of 2.5-h infusion of dobutamine (5 mcg/kg/min fixed-dose) or placebo in 20 septic shock patients with cardiac index ≥2.5 l/min/m² and hyperlactatemia. Primary outcome was sublingual perfused microvascular density.

Results

Despite an increasing cardiac index, heart rate and left ventricular ejection fraction, dobutamine had no effect on sublingual perfused vessel density [9.0 (7.9–10.1) vs. 9.1 n/mm (7.9–9.9); p = 0.24] or microvascular flow index [2.1 (1.8–2.5) vs. 2.1 (1.9–2.5); p = 0.73] compared to placebo. No differences between dobutamine and placebo were found for the lactate levels, mixed venous-arterial pCO₂ gradient, thenar muscle oxygen saturation, capillary refill time or gastric-to-arterial pCO₂ gradient. The indocyanine green plasma disappearance rate [14.4 (9.5–25.6) vs. 18.8 %/min (11.7–24.6); p = 0.03] and the recovery slope of thenar muscle oxygen saturation after a vascular occlusion test [2.1 (1.1–3.1) vs. 2.5 %/s (1.2–3.4); p = 0.01] were worse with dobutamine compared to placebo.

Conclusions

Dobutamine failed to improve sublingual microcirculatory, metabolic, hepatosplanchnic or peripheral perfusion parameters despite inducing a significant increase in systemic hemodynamic variables in septic shock patients without low cardiac output but with persistent hypoperfusion.     

Prevalence of endotoxemia after surgery and its association with ICU length of stay

Introduction

The aim of this observational study was to investigate the prevalence of endotoxemia after surgery and its association with ICU length of stay.

Methods

102 patients admitted to a university ICU after surgery were recruited. Within four hours of admission, functional data were collected and APACHE II severity score calculated. Arterial blood samples were taken and endotoxemia was measured by chemiluminescence (Endotoxin Activity (EA)). Patients were stratified according to their endotoxin levels (low, intermediate and high) and according to their surgical procedures. Differences between endotoxin levels were assessed by ANOVA, accepting P < 0.05 as significant. Data are expressed as mean ± SD.

Results

EA levels were low in 68 (66%) patients, intermediate in 17 (17%) and high in 17 (17%). Age (61 ± 17 years) and APACHE II score 8.3 ± 3.7 (P = 0.542) were not significantly different in the three EA groups. Functional parameters on admission were similar between EA groups: white blood cells 11093 ± 4605 cells/mm³ (P = 0.385), heart rate 76 ± 16 bpm (P = 0.898), mean arterial pressure 88.8 ± 13.6 mmHg (P = 0.576), lactate 1.18 ± 0.77 mmol/L (P = 0.370), PaO₂/FiO₂ 383 ± 109 mmHg (P = 0.474). Patients with high levels of EA were characterized by longer length of stay in the ICU: 1.9 ± 3.0 days in the low EA group, 1.8 ± 1.4 days in intermediate and 5.2 ± 7.8 days in high group (P = 0.038).

Conclusions

17% of our patients were characterized by high levels of endotoxemia as assessed by EA assay, despite their low level of complexity on admission. High levels of endotoxin were associated with a longer ICU length of stay.     

Impact of type 2 diabetes mellitus and glucose control on fractional flow reserve measurements in intermediate grade coronary lesions

Background

Hemodynamic relevance of intermediate grade coronary stenoses is accurately assessed by fractional flow reserve (FFR) measurements. However, the reliability of FFR in patients with type 2 diabetes mellitus (DM) and inadequate glucose control (IGC) is incompletely explored. This study aimed to investigate the impact of DM and IGC on the relationship between FFR measurements and quantitative coronary angiography (QCA)-derived morphological parameters.

Methods

We performed FFR and QCA in 266 intermediate grade lesions of 224 patients (113 non-DM and 111 DM) with stable coronary artery disease. Diabetic patients were categorized into groups with adequate (Hb_A1C <7 %) and inadequate (Hb_A1c ≥7 %) glucose control.

Results

Intermediate grade lesions from all-DM versus non-DM patients differed significantly in lesion length (LL) (10.91 ± 5.79 mm versus 9.23 ± 3.85 mm, p = 0.005) and hemodynamic relevance (FFR ≤0.8, 37.7 % versus 24.2 %, p = 0.018). FFR measurements in non-DM, all-DM and DM-IGC patients correlated significantly with percent diameter stenosis (%DS) [non-DM: r ² = 0.075 (p = 0.007); all-DM: r ² = 0.254 (p < 0.001), DM-IGC: r ² = 0.301 (p < 0.001)] and LL [non-DM: r ² = 0.356; all-DM: r ² = 0.580, DM-IGC: r ² = 0.513 (all p < 0.001)]. There was a better correlation between FFR and both %DS (p = 0.022) and LL (p = 0.011) among all-DM compared to non-DM patients. Receiver-operating curve analysis demonstrated that among all QCA-derived parameters LL had the best diagnostic efficacy to predict FFR ≤0.8 for non-DM (AUC 0.911, 95 % CI 0.861–0.960, best cut-off value 9.22 mm), all-DM (AUC 0.967, 95 % CI 0.942–0.991, best cut-off value 9.97 mm) and DM-IGC (AUC 0.960, 95 % CI 0.920–0.999, best cut-off value 9.97 mm) patients.

Conclusion

Our data in intermediate grade lesions suggest that FFR is reliable in DM patients and LL is the best predictor for hemodynamic relevance in patients without and with diabetes, irrespective of the glycemic state.     

Ivabradine therapy to unmask heart rate-independent effects of β-blockers on pulse wave reflections

Background

Prior studies suggest that β-blockers lead to increased pulse wave reflections, thereby negating the blood pressure lowering effects on cardiovascular mortality. Parts of these effects may be induced by the heart rate reduction under β-blockade. The aim of this study was to unmask heart rate-independent effects of β-blockade on pulse wave reflections by switching therapy from β-blockers to ivabradine, an I _f channel inhibitor without impact on systemic hemodynamics.

Methods

14 male patients (age 61 ± 3 years, LVEF 62 ± 1 %) with arterial hypertension and coronary artery disease (CAD) under chronic β-blocker therapy at moderate dosage and additional renin-angiotensin system-blocking therapy were included. We determined radial augmentation index (rAI) by radial applanation tonometry in patients under β-blockade both at rest and during early recovery after exercise. β-Blockers were then replaced by ivabradine. Six weeks later, patients were re-tested at rest and after exercise under ivabradine therapy.

Results

Mean heart rate (68 ± 3 vs. 63 ± 3 bpm; p = ns) and resting mean arterial pressure (98 ± 2 vs. 98 ± 2 mmHg; p = ns) were not different between β-blocker or ivabradine therapy, respectively. The rAI remained unchanged after switching therapy from β-blocker to ivabradine (86 ± 2 vs. 84 ± 4 %; p = ns). Post exercise, the rAI revealed an identical decrease in both groups (?7.2 ± 2.4 vs. ?5.4 ± 2.5 %, p = ns). The increase in heart rate between resting conditions and early recovery post exercise was inversely correlated with the decrease of rAI under β-blockade (r = ?0.70; p < 0.01) and showed a trend towards correlation under ivabradine (r = ?0.52; p = 0.07).

Conclusion

In men at the age of 60 years and CAD, β-blockade does not exert heart rate-independent, pleiotropic effects on peripheral pulse wave reflections, both at rest or after exercise. Our results fit well within recent studies, demonstrating the fundamental influence of heart rate on rAI.     

Pancreatic adenocarcinoma: a pilot study of quantitative perfusion and diffusion-weighted breath-hold magnetic resonance imaging

Purpose

To confirm the feasibility of breath-hold DCE-MRI and DWI at 3T to obtain the intra-abdominal quantitative physiologic parameters, K ^trans, k _ep, and ADC, in patients with untreated pancreatic ductal adenocarcinomas.

Methods

Diffusion-weighted single-shot echo-planar imaging (DW-SS-EPI) and dynamic contrast-enhanced (DCE) MRI were used for 16 patients with newly diagnosed biopsy-proven pancreatic ductal adenocarcinomas. K ^trans, k _ep, and apparent diffusion coefficient (ADC) values of pancreatic tumors, non-tumor adjacent pancreatic parenchyma (NAP), liver metastases, and normal liver tissues were quantitated and statistically compared.

Results

Fourteen patients were able to adequately hold their breath for DCE-MRI, and 15 patients for DW-SS-EPI. Four patients had liver metastases within the 6 cm of Z axis coverage centered on the pancreatic primary tumors. K ^trans values (10^?3 min^?1) of primary pancreatic tumors, NAP, liver metastases, and normal liver tissues were 7.3 ± 4.2 (mean ± SD), 25.8 ± 14.9, 8.1 ± 5.9, and 45.1 ± 15.6, respectively, k _ep values (10^?2 min^?1) were 3.0 ± 0.9, 7.4 ± 3.1, 5.2 ± 2.0, and 12.1 ± 2.8, respectively, and ADC values (10^?3 mm²/s) were 1.3 ± 0.2, 1.6 ± 0.3, 1.1 ± 0.1, and 1.3 ± 0.1, respectively. K ^trans, k _ep, and ADC values of primary pancreatic tumors were significantly lower than those of NAP (p < 0.05), while K ^trans and k _ep values of liver metastases were significantly lower than those of normal liver tissues (p < 0.05).

Conclusions

3T breath-hold quantitative physiologic MRI is a feasible technique that can be applied to a majority of patients with pancreatic adenocarcinomas.     

Door-to-implantation time of extracorporeal life support systems predicts mortality in patients with out-of-hospital cardiac arrest

Objective

This study aimed to identify predictors of mortality in patients with out-of-hospital cardiac arrest (OHCA) undergoing in-hospital extracorporeal life support system (ECLS) treatment.

Methods

We retrospectively studied the characteristics and clinical outcomes of 28 patients (January 2010 and December 2011) with OHCA and veno-arterial ECLS implemented during ongoing cardiopulmonary resuscitation (CPR) upon admission to the cath lab. Baseline left ventricular ejection fraction (LVEF) was determined after ECLS implantation and then every 24 h during and after successful weaning from ECLS.

Results

Overall 30-day survival rate was 39.3 % (11 of 28 patients). Baseline characteristics, initial laboratory measurements, and LVEF on admission were not significantly different between survivors and non-survivors. There was no difference regarding median CPR duration [survivors 44.0 min (IQR 31.0-45.0) vs. non-survivors 53.0 min (IQR 40.0-61.3); P = 0.23]. Door-to-ECLS implantation time was significantly longer in non-survivors [42.5 min (IQR 28.0–56.5) vs. 25.0 min (IQR 21.0–30.0); P < 0.01]. ECLS treatment duration was not significantly different between the two groups [survivors: 4.0 days (IQR 1.5–7.5) vs. non-survivors 6.5 days (IQR 1.0–8.0); P = 0.69]. LVEF significantly improved in survivors during ECLS treatment (mean ± SD survivor 47.5 ± 14.7 % vs. non-survivor 23.3 ± 14.9 %; P < 0.01). The door-to-ECLS implantation time was the only significant and independent predictor of 30-day mortality in multivariate Cox regression analysis (P = 0.04). Kaplan–Meier survival analysis showed a benefit favouring patients with a door-to-ECLS implantation time <30 min (log rank 6.29; P = 0.01).

Conclusion

A door-to-ECLS implantation time <30 min significantly improves 30-day outcomes in patients with OHCA.     

Increasing arterial blood pressure with norepinephrine does not improve microcirculatory blood flow: a prospective study

Introduction

Our goal was to assess the effects of titration of a norepinephrine infusion to increasing levels of mean arterial pressure (MAP) on sublingual microcirculation.

Methods

Twenty septic shock patients were prospectively studied in two teaching intensive care units. The patients were mechanically ventilated and required norepinephrine to maintain a mean arterial pressure (MAP) of 65 mmHg. We measured systemic hemodynamics, oxygen transport and consumption (DO₂ and VO₂), lactate, albumin-corrected anion gap, and gastric intramucosal-arterial PCO₂ difference (ΔPCO₂). Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. After basal measurements at a MAP of 65 mmHg, norepinephrine was titrated to reach a MAP of 75 mmHg, and then to 85 mmHg. Data were analyzed using repeated measurements ANOVA and Dunnett test. Linear trends between the different variables and increasing levels of MAP were calculated.

Results

Increasing doses of norepinephrine reached the target values of MAP. The cardiac index, pulmonary pressures, systemic vascular resistance, and left and right ventricular stroke work indexes increased as norepinephrine infusion was augmented. Heart rate, DO₂ and VO₂, lactate, albumin-corrected anion gap, and ΔPCO₂ remained unchanged. There were no changes in sublingual capillary microvascular flow index (2.1 ± 0.7, 2.2 ± 0.7, 2.0 ± 0.8) and the percent of perfused capillaries (72 ± 26, 71 ± 27, 67 ± 32%) for MAP values of 65, 75, and 85 mmHg, respectively. There was, however, a trend to decreased capillary perfused density (18 ± 10,17 ± 10,14 ± 2 vessels/mm², respectively, ANOVA P = 0.09, linear trend P = 0.045). In addition, the changes of perfused capillary density at increasing MAP were inversely correlated with the basal perfused capillary density (R² = 0.95, P < 0.0001).

Conclusions

Patients with septic shock showed severe sublingual microcirculatory alterations that failed to improve with the increases in MAP with norepinephrine. Nevertheless, there was a considerable interindividual variation. Our results suggest that the increase in MAP above 65 mmHg is not an adequate approach to improve microcirculatory perfusion and might be harmful in some patients.     

Assessment of the inflammatory effect of low-dose oxygen in mechanically ventilated patients

Purpose

Although low doses of oxygen (FiO₂ <0.50) are considered nontoxic, recent studies have shown that even lower doses increase pulmonary inflammatory mediators. We aimed to evaluate the acute effects of reducing FiO₂ on pulmonary inflammation in mechanically ventilated patients without respiratory failure.

Methods

This study was a prospective, single-center crossover study in a medical/surgical intensive care unit at a university hospital. Hemodynamically stable patients under mechanical ventilation for >24 h without severe respiratory failure (PaO₂/FiO₂ >250). A basal FiO₂ of 0.40 was reduced to 0.21 provided SpO₂ remained higher than 90 %. Patients who could not tolerate the reduction in FiO₂ to 0.21 were excluded.

Results

We screened 40 patients, but only 28 (70 %) tolerated FiO₂ 0.21. We measured common clinical variables and inflammatory mediators in plasma and in exhaled breath condensate (EBC) at the end of three 4-h periods: (1) basal (FiO₂ 0.40), (2) after FiO₂ reduction to 0.21, and (3) after returning FiO₂ 0.40. We used one-way ANOVA for repeated measurements with FiO₂ as the grouping variable. Median values of inflammatory mediators in EBC showed nonsignificant changes among the three periods: NO₂ + NO₃ 17.1, 14.1 and 11.0 μmol/L (p = 0.2), and 8-isoprostane 4.4, 8.2 and 5.3 pg/ml (p = 0.6) for the three periods, respectively. Plasma levels also showed nonsignificant changes during the period of the study: NO₂ + NO₃ 12.6, 16.3 and 15.0 μmol/L (p = 0.9), TNFα 13.5, 18.0 and 14.5 pg/ml (p = 0.8), IL-4 12.9, 18.7 and 23.9 pg/ml (p = 0.1), IL-6 50.9, 35.1 and 28.3 pg/ml (p = 0.6), and IL-10 15.2, 22.2 and 22.2 pg/ml (p = 0.7) for the three periods, respectively.

Conclusion

FiO₂ 0.40 in mechanically ventilated patients without severe respiratory failure did not increase systemic or pulmonary inflammation.     

The effects of exercise at high altitude on high-sensitivity cardiac troponin release and associated biventricular cardiac function

Background

It has been consistently shown that heavy exercise leads to cardiac troponin (cTn) release and variable changes in post exercise cardiac function. This relationship has not been explored at increasing or significant high altitude (HA). This study assessed the effects of exercise at progressively increasing HA on high-sensitivity (hs)-cTnT levels and their relationship to biventricular cardiac function and severity of acute mountain sickness (AMS).

Methods

Transthoracic echocardiograms, hs-cTnT levels and AMS scores were measured at rest at 1,300 m then repeated post exercise and 12 h later after progressive trekking to 3,440, 4,270 m and at 5,150 m (after trekking to 5,643 m) on 19 healthy subjects (age 35.4 ± years, 52.6 % males).

Results

There was a detectable increase (>5 ng/L) in post exercise hs-cTnT with exercise at HA which became significant at 5,150 m (5.84 % at 3,440 m, 5.2 % at 4,270 m and 56.3 % at 5,150 m; p = 0.0005). Compared with baseline, HA to 5,150 m led to a significant rise in post exercise Lake Louis AMS scores (p < 0.001) pulmonary artery systolic pressure (PASP) (23.7 ± 3.8 vs 37.9 ± 11.7 mmHg: p < 0.001), cardiac output (5.2 ± 1.2 vs 7.5 ± 1.3 l/min; p < 0.001) and a fall in SpO₂ (96.1 ± vs 77.4 ± 12.0 %; p < 0.001). There was no change in stroke volume (p = 0.10) or estimated filling pressures (E/E’) of the left (p = 0.50) and right ventricles (p = 0.4). On multivariate analysis increasing cardiac output (p = 0.02) and PASP (p = 0.04) and decreasing SpO₂ (p = 0.01) were the only independent predictors of increasing cTnT levels (overall R ² = 0.23, p < 0.0001).

Conclusions

Moderate intensity exercise at significant HA influences the post exercise increase in hs-cTnT without overt deleterious effects on cardiac function.