Validating a pragmatic definition of shock in adult patients presenting to the ED.

OBJECTIVE: The importance of the early recognition of shock in patients presenting to emergency departments is well recognized, but at present, there is no agreed practical definition for undifferentiated shock. The main aim of this study was to validate an a priori clinical definition of shock against 28-day mortality. DESIGN, SETTING AND SUBJECTS: This prospective, observational, cross-sectional, single-center study was conducted in Hong Kong, China. Data were collected between July 1, 2012, and January 31, 2013. An a priori definition of shock was designed, whereby patients admitted to the resuscitation room or high dependency area of the emergency department were divided into 1 of 3 groups-no shock, possible shock, and shock. The primary outcome was 28-day mortality. Secondary outcomes were in-hospital mortality or admission to the intensive or coronary care unit. MEASUREMENTS AND MAIN RESULTS: A total of 111 patients (mean age, 67.2 ± 17.1 years; male = 69 [62%]) were recruited, of which 22 were classified as no shock, 54 as possible shock, and 35 as shock. Systolic blood pressure, mean arterial pressure, lactate, and base deficit correlated well with shock classifications (P < .05). Patients who had 3 or more positively defined shock variables had a 100% poor composite outcome rate (5 of 5). Patients with 2 shock variables had a 66.7% (4 of 6) poor composite outcome rate. CONCLUSIONS: A simple, practical definition of undifferentiated shock has been proposed and validated in a group of patients presenting to an emergency department in Hong Kong. This definition needs further validation in a larger population and other settings.

Noninvasive transcutaneous Doppler ultrasound-derived hemodynamic reference ranges in Chinese adolescents.

OBJECTIVES: The ultrasonic cardiac output monitor is a noninvasive, quantitative method for measuring and monitoring cardiovascular hemodynamic parameters in patients. The aims of this study were first to establish reference ranges for cardiovascular indices measured by the ultrasonic cardiac output monitor in Chinese children aged 12-18 yr, second to assess the interobserver reliability of the method, and third to compare these ranges with a Caucasian group from Australia. DESIGN, SETTING, AND SUBJECTS: This was a population-based cross-sectional cohort study of Chinese adolescents 12-18 years old, performed in secondary schools in Hong Kong. INTERVENTIONS: Ultrasonic cardiac output monitor scans were performed on each subject to measure stroke volume, cardiac output, and systemic vascular resistance together with standard oscillometric measurement of blood pressure and heart rate. Ultrasonic cardiac output monitor parameters were also standardized by deriving body surface area referenced indices. Normal ranges were defined as lying within two standard deviations on either side of the mean. To assess interobserver variability, a second, blinded operator repeated 17% of scans. MEASUREMENTS AND MAIN RESULTS: A total of 590 Chinese adolescents (49% boys) were scanned. Normal ranges for cardiac output, cardiac index, stroke volume, stroke volume index, stroke volume resistance, and systemic vascular resistance index are presented. Males had a significantly higher mean stroke volume, cardiac output, and systemic vascular resistance index compared with females (p < 0.05), but no significant differences were found for the indexed values. When compared with a group of 31 Australian Caucasian adolescents (71% boys), Chinese adolescents have a significantly lower cardiac output and stroke volume (p <0.05), but these differences disappeared when adjusted for body surface area (i.e., stroke volume index, cardiac index, and systemic vascular resistance index). Interobserver variability of ultrasonic cardiac output monitor-derived stroke volume showed a coefficient of variation of 10.2%, a correlation coefficient of 0.90 (95% confidence interval 0.85-0.93), while Bland-Altman analysis showed a mean bias of 1.5% (95% limits of agreement were -19.9% to 23.0%). CONCLUSIONS: This study presents normal values for cardiovascular indices in Chinese adolescents using the ultrasonic cardiac output monitor. When referenced to body surface area, the differences between Caucasians and Chinese were insignificant.

Real-time dose adjustment using point-of-care platelet reactivity testing in a double-blind study of prasugrel in children with sickle cell anaemia.

Patients with sickle cell anaemia (SCA) have vaso-occlusive crises resulting from occlusive hypoxic-ischaemic injury. Prasugrel inhibits platelet activation and aggregation involved in SCA pathophysiology. Determining Effects of Platelet Inhibition on Vaso-Occlusive Events (DOVE) was a phase 3, double-blind, randomised, placebo-controlled trial assessing prasugrel efficacy. DOVE sought to bring patients' P2Y12 reaction unit (PRU) value within a targeted range via prasugrel dose adjustments using encrypted VerifyNow P2Y12® (VN-P2Y12) point-of-care testing and an interactive voice-response system (IVRS). After PRU determination, randomised patients received 0.08 mg/kg/day prasugrel or placebo. Encrypted PRUs and IVRS provided double-blind dose adjustments to achieve a defined PRU target range of 136-231; placebo patients had mock titrations. Of 341 randomised patients, 166 placebo and 160 prasugrel patients reached the fully titrated dose (FTD). Most prasugrel patients (n=104, 65 %) remained on the initial 0.08 mg/kg dose; doses escalations occurred in 23 % of patients (n=36). Mean PRUs for the pharmacodynamic population at baseline were similar in the prasugrel (273 ± 44.9) and placebo groups (273 ± 51.7), with significant reductions in PRU (p<0.001) for prasugrel patients at the FTD and at 9 months. Concomitant use of hydroxyurea did not affect platelet reactivity at any time. The majority of prasugrel patients (n=135, 84.4 %) at the FTD were within the target range of 136-231 PRUs. Mean VN-P2Y12 percentage inhibition at baseline was similar in the prasugrel (2.8 ± 5.4 %) and placebo groups (2.0 ± 4.7 %); prasugrel patients had significant increases in inhibition (p<0.001) at FTD and at 9 months. Patients with higher PRU values at baseline required higher prasugrel doses to bring PRU within the prespecified range. DOVE is the first study to successfully employ double-blind, real-time, encrypted, point-of-care platelet testing and IVRS to dose-adjust antiplatelet therapy to a targeted range of platelet inhibition.

The normal ranges of cardiovascular parameters measured using the ultrasonic cardiac output monitor.

The ultrasonic cardiac output monitor (USCOM) is a noninvasive transcutaneous continuous wave Doppler method for assessing hemodynamics. There are no published reference ranges for normal values in adults (aged 18-60 years) for this device. This study aimed to (1) measure cardiovascular indices using USCOM in healthy adults aged 18-60 years; (2) combine these data with those for healthy children (aged 0-12), adolescents (aged 12-18), and the elderly (aged over 60) from our previously published studies in order to present normal ranges for all ages, and (3) establish normal ranges of USCOM-derived variables according to both weight and age. This was a population-based cross-sectional observational study of healthy Chinese subjects aged 0.5-89 years in Hong Kong. USCOM scans were performed on all subjects, to produce measurements including stroke volume, cardiac output, and systemic vascular resistance. Data from previously published studies (children, adolescents, and the elderly) were included. Normal ranges were defined as lying between the 2.5th and 97.5th percentiles. A total of 2218 subjects were studied (mean age = 16.4, range = 0.5-89; 52% male). From previous studies, 1197 children (aged 0-12, 55% male), 590 adolescents (aged 12-18, 49% male), and 77 elderly (aged 60-89, 55% male) were included. New data were collected from 354 adults aged 18-60 (47% male). Normal ranges are presented according to age and weight. We present comprehensive normal ranges for hemodynamic parameters obtained with USCOM in healthy subjects of all ages from infancy to the elderly.

Age-specific non-invasive transcutaneous Doppler ultrasound derived haemodynamic reference ranges in elderly Chinese adults.

BACKGROUND: Whilst there is a presumption in medicine that ageing adversely affects cardiovascular function, it is unknown if resting haemodynamics are compromised in the elderly, and if so, to what degree. This study was intended to answer several questions; whether age-related changes in haemodynamics occur; whether there was a difference between the haemodynamics of ageing subjects with and without mild chronic disease; whether there was a difference in haemodynamics as measured from either the aortic or the pulmonary valve; and to establish reference ranges for this population. METHODS: Chinese adults aged over 60 years were divided into three age bands of 61-70, 71-80 and over 80 years. The haemodynamic parameters were measured using a non-invasive Doppler ultrasound-based instrument, the Ultrasonic Cardiac Output Monitor (USCOM). RESULTS: One hundred and sixty-five subjects (48.5% males) were recruited. 78 (47.3%) had no known disease whilst 87 (52.7%) had mild chronic illness. A total of 21 individual haemodynamic parameters were measured or calculated for each subject. There were no significant differences in stroke volume (SV), cardiac output (CO), systemic vascular resistance (SVR) or in body surface area (BSA)-indexed parameters, SV index (SVI), cardiac index (CI) and SVR index (SVRI) across age groups, or in other indexed haemodynamic parameters. No significant differences in indexed haemodynamics were found between those subjects with and those without mild chronic disease. Small, statistically significant, but clinically insignificant, differences (< 5%) were found between the aortic and pulmonary valve measurements for SV, SVI and heart rate. CONCLUSIONS: Ageing does not have any significant effect on resting haemodynamics in the elderly population studied. Mild chronic disease does not adversely affect resting haemodynamics in this population. GENERAL SIGNIFICANCE: Reference ranges were established for 21 haemodynamic parameters, as measured by USCOM, for an elderly Chinese population but not for non-Chinese populations.

Influence of different positions on hemodynamics derived from noninvasive transcutaneous Doppler ultrasound.

A proper alignment of the ultrasound beam to the aortic or pulmonary outflow tracts is essential to acquire accurate signals. This study aimed to investigate the influence of different positions on the acquisition of Doppler signals using a noninvasive transcutaneous Doppler ultrasound. This was a prospective observational crossover study. Two operators performed hemodynamics measurements on each subject in supine, sitting, semirecumbent, passive leg raising (PLR) 20°, and PLR 60° positions using both aortic and pulmonary approaches. All Doppler flow profile images were assessed using the Fremantle and Prince of Wales Hospital criteria. Time required to obtain Doppler signals was recorded. A total of 60 subjects (50% males) aged 18-60 years old were investigated. In both sitting and semirecumbent positions, aortic stroke volume indexes (SVIs) and cardiac indexes (CIs) were significantly lower than those in the other three positions while the pulmonary CIs were comparable to that in the supine position. In the sitting position, the aortic signal qualities were lower and the time to obtain the pulmonary Doppler signals was prolonged. Instead, the signal quality and the time to obtain the Doppler signals in the semirecumbent position were similar to those in the other three positions using the pulmonary approach. PLR did not cause a significant increase in SVI regardless of the degree of leg elevation. These data show that it is feasible to perform the noninvasive transcutaneous Doppler ultrasound using the pulmonary approach in the semirecumbent position for patients unable to maintain the supine position. The aortic approach in the sitting and semirecumbent positions is not suitable as it is not sufficiently reliable.

Measurement of systemic oxygen delivery and inotropy in healthy term neonates with the Ultrasonic Cardiac Output Monitor (USCOM).

INTRODUCTION: The aim of this study was to assess the normal values for Smith-Madigan inotropy (SMI), Smith-Madigan inotropy index (SMII), oxygen delivery (DO2) and oxygen delivery index DO2I in healthy term neonates on the first day of life and during circulatory adaptation over the first three days of life. METHODS: Hemodynamics of the left heart were measured non-invasively in 71 normal full-term neonates over the first three days using the Ultrasonic Cardiac Output Monitor (USCOM). This was combined with hemoglobin concentration from umbilical cord blood and pulse oximetry to calculate DO2 and DO2I. Blood pressure was measured using automated oscillometry and combined with the hemodynamic measures and hemoglobin concentration using the Smith-Madigan method to calculate inotropy (SMI) and inotropy index (SMII). RESULTS: SMI and SMII showed no significant change during the study period, ranging from 154 to 168 mW and 694 to 731 mW/m(2). Mean (SD) DO2 and DO2I showed a significant fall over three days from 131 (63) ml/min and 596 (278) ml/m(2)/min to 118 (46) ml/min and 517 (173) ml/m(2)/min (p<0.01 and <0.001 respectively) with a corresponding decrease in cardiac output from 758 (143) ml/min to 658 (131) ml/min, (p=0.002). There was no significant change in stroke volume, heart rate, SMI or SMII within the first day. DO2 and DO2I showed small but significant decreases within the first day from 153 (46) ml/min and 699 (174) ml/min/m(2) to 129 (36) ml/min and 609 (141) ml/min/m(2) (p=0.017 and 0.048 respectively). CONCLUSIONS: Normal inotropy of the left heart and systemic DO2 values in healthy full-term neonates over the first three days of life were assessed using the USCOM. Subjects showed stable myocardial contractility over the first three days with decreasing DO2 and DO2I in line with the decrease in cardiac output (CO). DO2 and DO2I showed small but significant reductions during the first 24 h. USCOM proved to be a feasible and convenient non-invasive bedside tool to assess inotropy and oxygen delivery in neonates.

Accuracy of the ultrasonic cardiac output monitor in healthy term neonates during postnatal circulatory adaptation.

BACKGROUND: Echocardiography is regarded as a gold standard for measuring hemodynamic values. The ultrasonic cardiac output monitor (USCOM) is a new method for measuring hemodynamics and could provide non-invasive point of care guidance. So far, there are no published USCOM reference values for neonates, nor has USCOM's accuracy been established in this population. We aimed to determine the accuracy and clinical utility of the USCOM in healthy neonates relative to published echocardiographic data, to establish normal hemodynamic parameters that it measures, and to assess the possible role of USCOM as an alternative to echocardiography as a trend monitor. METHODS: Right and left heart hemodynamics of 90 normal neonates were measured during circulatory adaptation over the first three days of life using the USCOM and automated oscillotonometry. RESULTS: Heart rate showed a significant decline from days one to three, from 126 to 120 (P < 0.001). Systolic, diastolic and mean arterial pressures all increased significantly from 66 to 71 mmHg, 33 to 38 mmHg and 44 to 49 mmHg, respectively (P < 0.001 in each case). Right ventricular cardiac index (RV-CI) showed no change with a mean of 5.07 L × min(-1) × m(-2). Left ventricular cardiac index (LV-CI) declined from 3.43 to 3.00 L × min(-1) × m(-2) (P < 0.001). RV-CI exceeded LV-CI on all three days by a mean of 61%. The systemic vascular resistance index (SVRI), based on LV-CI, increased significantly over the three days from 1083 to 1403 dyne × sec × cm(-5) × m(2) (P < 0.001). CONCLUSIONS: Normal neonatal hemodynamic values, as indicated by USCOM, were established. LV-CI measurement showed excellent agreement with published echocardiographic studies. RV-CI was constant and exceeded LV-CI for all three days of this study. It may be falsely high due to flow velocity measurement errors arising from the pulmonary branch arteries, and may represent a limitation of the USCOM method. The progressive rise of arterial pressure and SVRI despite a declining LV-CI may indicate functional closure of the ductus arteriosus, with the greatest change occurring within the first 24 hours. Evidence of closure of the foramen ovale was not observed.