Association Between Thromboelastometry Identified Hypercoagulability and Thromboembolic Complications After Arthroplasty: A Prospective Observational Study in Patients With Obesity.

The prothrombotic state of obesity can increase the risk of thromboembolism. We aimed to investigate if there was an association between baseline hypercoagulable rotational thromboelastometry (ROTEM) profile and thromboembolic complications in arthroplasty patients with obesity. Patients with a body mass index ≥ 25 kg/m2 and/or waist circumference ≥94 cm (M) and 80 cm (F) undergoing hip and knee arthroplasty had pre- and postoperative ROTEM. ROTEM values were compared by outcome status using an independent sample equal-variance t-test. Of the 303 total participants, hypercoagulability defined as extrinsically activated thromboelastometry maximum clot firmness G score ≥ 11 K dyne/cm2, was observed in 90 (30%) of the 300 participants with preoperative ROTEM assays. Clinically significant thromboembolic complications occurred in 5 (1.7%) study participants before discharge and in 10 (3.3%) by 90 days. These included 6 with pulmonary emboli, 3 with deep venous thrombus, and 1 with myocardial infarction. We found no evidence for an association between baseline hypercoagulability and incident thromboembolic events, analysis limited by the number of events. Postoperative decrease in platelets and an increase in fibrinogen were observed. ROTEM parameter changes differed across obesity categories.

Associations Between Socioeconomic Status, Patient Risk, and Short-Term Intensive Care Outcomes.

OBJECTIVES: To investigate the association of socioeconomic status as measured by the average socioeconomic status of the area where a person resides on short-term mortality in adults admitted to an ICU in Queensland, Australia. DESIGN: Secondary data analysis using de-identified data from the Australian and New Zealand Intensive Care Society Centre for Outcome and Resource Evaluation linked to the publicly available area-level Index of Relative Socioeconomic Advantage and Disadvantage from the Australian Bureau of Statistics. SETTING: Adult ICUs from 35 hospitals in Queensland, Australia, from 2006 to 2015. PATIENTS: A total of 218,462 patient admissions. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The outcome measure was inhospital mortality. The main study variable was decile of Index of Relative Socioeconomic Advantage and Disadvantage. The overall crude inhospital mortality was 7.8%; 9% in the most disadvantaged decile and 6.9% in the most advantaged decile (p < 0.001). Increasing socioeconomic disadvantage was associated with increasing severity of illness as measured by Acute Physiology and Chronic Health Evaluation III score, admission with a diagnosis of sepsis or trauma, cardiac, respiratory, renal, and hepatic comorbidities, and remote location. Increasing socioeconomic advantage was associated with elective surgical admission, hematological and oncology comorbidities, and admission to a private hospital (all p < 0.001). After excluding patients admitted after elective surgery, in the remaining 106,843 patients, the inhospital mortality was 13.6%, 13.3% in the most disadvantaged, and 14.1% in the most advantaged. There was no trend in mortality across deciles of socioeconomic status after excluding elective surgery patients. In the logistic regression model adjusting for severity of illness and diagnosis, there was no statistically significant difference in the odds ratio of inhospital mortality for the most disadvantaged decile compared with other deciles. This suggests variables used for risk adjustment may lie on the causal pathway between socioeconomic status and outcome in ICU patients. CONCLUSIONS: Socioeconomic status as defined as Index of Relative Socioeconomic Advantage and Disadvantage of the area in which a patient lives was associated with ICU admission diagnosis, comorbidities, severity of illness, and crude inhospital mortality in this study. Socioeconomic status was not associated with inhospital mortality after excluding elective surgical patients or when adjusted for severity of illness and admission diagnosis. Commonly used measures for risk adjustment in intensive care improve understanding of the pathway between socioeconomic status and outcomes.

Are pressure injuries related to skin failure in critically ill patients?

BACKGROUND: Pressure injuries contribute significantly to patient morbidity and healthcare costs. Critically ill patients are a high risk group for pressure injury development and may suffer from skin failure secondary to hypoperfusion. The aim of this study was to report hospital acquired pressure injury incidence in intensive care and non-intensive care patients; and assess the clinical characteristics and outcomes of ICU patients reported as having a hospital acquired pressure injury to better understand patient factors associated with their development in comparison to ward patients. METHODS: The setting for this study was a 630 bed, government funded, tertiary referral teaching hospital. A secondary data analysis was undertaken on all patients with a recorded PI on the hospital's critical incident reporting systems and admitted patient data collection between July 2006 to March 2015. RESULTS: There were a total of 5280 reports in 3860 patients; 726 reports were intensive care patients and 4554 were non-intensive care patients, with severe hospital acquired PI reported in 22 intensive care patients and 54 non-intensive care patients. Pressure injury incidence increased in intensive care patients and decreased in non-intensive care patients over the study period. There were statistically significant differences in the anatomical location of severe hospital acquired pressure injuries between these groups (p=0.008). CONCLUSION: Intensive care patients have greater than 10-fold higher hospital acquired pressure injury incidence rates compared to other hospitalised patients. The predisposition of critically ill patients leaves them susceptible to pressure injury development despite implementation of pressure injury prevention strategies. Skin failure appears to be a significant phenomenon in critically ill patients and is associated with the use of vasoactive agents and support systems such as extra corporeal membrane oxygenation and mechanical ventilation.

Identification and assessment of potentially high-mortality intensive care units using the ANZICS Centre for Outcome and Resource Evaluation clinical registry.

PURPOSE: A hospital's highest-risk patients are managed in the intensive care unit. Outcomes are determined by patients' severity of illness, existing comorbidities and by processes of care delivered. The Australian and New Zealand Intensive Care Society (ANZICS) Centre for Outcome and Resource Evaluation (CORE) manages a binational clinical registry to benchmark performance, and report and assess ICUs which appear to have worse outcomes than others. METHODS: A descriptive retrospective cohort study was undertaken to detail processes, outcomes, limitations and practical lessons learnt from monitoring ICU performance throughout Australia and New Zealand. All ICUs contributing to the ANZICS Adult Patient Database between 2009 and 2014 were included. A potential outlier ICU was defined as one with a statistically significantly higher standardised mortality ratio (SMR) than its peer group. RESULTS: There were 757 188 admissions to 168 ICUs. Of these, 27 ICUs (16%) were identified as potential outlier ICUs at least once. Data quality problems led to inaccurate or artificially elevated SMRs at 16/27 ICUs. Variation in diagnostic casemix partly or completely explained the elevated SMR at 15/27 ICUs. At nine ICUs where data quality and casemix differences did not explain the elevated SMR, process-of-care problems were identified. CONCLUSIONS: A combination of routine monitoring techniques, statistical analysis and contextual interpretation of findings is required to ensure potential outlier ICUs are appropriately identified. This ensures engagement and understanding from clinicians and jurisdictional health departments, while contributing to the improvement of ICU practices throughout Australia and New Zealand.

Measuring the quality of perioperative care in cardiac surgery.

Quality of care is of increasing importance in health and surgical care. In order to maintain and improve quality, we must be able to measure it and identify variation. In this narrative review, we aim to identify measures used in the assessment of quality of care in cardiac surgery and to evaluate their utility. The electronic databases Pubmed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews, and CINAHL were searched for original published studies using the terms 'cardiac surgery' and 'quality or outcome or process or structure' as either keywords in the title or text or MeSH terms. Secondary searches and identification of references from original articles were carried out. We found a total of 54 original articles evaluating measurements of quality. While structure, process, and outcome indicators remain the mainstay of quality measurement, new and innovative methods of risk assessment have improved reliability and discrimination. Continuous assessment provides a promising method of both maintaining and improving quality of care. Future studies should focus on long-term and patient-centred outcomes, such as quality-of-life measures.

Quantification of perflutren microsphere contrast destruction during transit through an ex vivo extracorporeal membrane oxygenation circuit.

BACKGROUND: Echocardiography is a key investigation in the management of patients on extracorporeal membrane oxygenation (ECMO). However, echocardiographic images are often non-diagnostic in this patient population. Contrast-enhanced echocardiography may overcome many of these limitations but contrast microspheres are hydrodynamically labile structures prone to destruction from shear forces and turbulent flow, which may exist within an ECMO circuit. This study sought to evaluate microsphere destruction (utilising signal intensity as a marker of contrast concentration) during transit through an ECMO circuit. METHODS: Activated Definity® contrast was diluted to 50 ml with normal saline and infused into a crystalloid primed ex vivo ECMO with a Quadrox oxygenator at 150 ml/h. Imaging was performed on pre- and post-pump head/oxygenator sections of the circuit using a Philips iE33 scanner and S5-1 transducer. Five-millimetre regions of interest were placed in the centre of the ultrasound field. Average signal intensity (decibels) was calculated at speeds of 1000, 2000, 3000 and 4000 rpm and then repeated with an infusion rate of 300 ml/h. The oxygenator was then spliced out of the circuit and the measures repeated. RESULTS: There was a significant reduction in contrast concentration during passage through the ECMO circuit at all speeds (with higher pump head speeds resulting in greater microsphere destruction). In a circuit with an oxygenator, relative decrease in signal intensity was 21.4 versus 5.2 % without an oxygenator. There was significant destruction of contrast microspheres during passage through the ECMO circuit at all pump head speeds. An oxygenator contributed to microsphere destruction at a significantly greater level than the pump head alone. There was no significant difference in mean signal intensity reduction in the circuit between an infusion of 150 or 300 ml/h (3.5 ± 3.2 versus 3.6 ± 2.5 dB, respectively, p = 0.79). CONCLUSIONS: Flow of contrast through an ECMO circuit results in significant destruction of microspheres. Circuits with an oxygenator result in significantly greater levels of contrast destruction than by the pump head alone. Clinicians should be cognisant of the relationship between ECMO circuit configurations, pump head speed and contrast destruction when performing a contrast-enhanced echocardiogram in patients supported with ECMO.

Successful use of pre and post-operative ECMO for pulmonary endarterectomy, mitral valve replacement and myomectomy in a patient with chronic thromboembolic pulmonary hypertension and hypertrophic cardiomyopathy.

As a salvage strategy, extracorporeal membrane oxygenation (ECMO) permits the recovery of end-organ perfusion, whilst allowing the surgeon time for patient reassessment and surgical planning. We report upon the first known case in which VA ECMO was instituted as peri-operative supportive therapy for a young patient, in-extremis, with surgically correctable Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Hypertrophic Cardiomyopathy (HOCM).

Protein-bound drugs are prone to sequestration in the extracorporeal membrane oxygenation circuit: results from an ex vivo study.

INTRODUCTION: Vital drugs may be degraded or sequestered in extracorporeal membrane oxygenation (ECMO) circuits, with lipophilic drugs considered to be particularly vulnerable. However, the circuit effects on protein-bound drugs have not been fully elucidated. The aim of this experimental study was to investigate the influence of plasma protein binding on drug disposition in ex vivo ECMO circuits. METHODS: Four identical ECMO circuits comprising centrifugal pumps and polymethylpentene oxygenators and were used. The circuits were primed with crystalloid, albumin and fresh human whole blood and maintained at a physiological pH and temperature for 24 hours. After baseline sampling, known quantities of study drugs (ceftriaxone, ciprofloxacin, linezolid, fluconazole, caspofungin and thiopentone) were injected into the circuit to achieve therapeutic concentrations. Equivalent doses of these drugs were also injected into four polypropylene jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the controls and the ECMO circuits over 24 hours, and the concentrations of the study drugs were quantified using validated chromatographic assays. A regression model was constructed to examine the relationship between circuit drug recovery as the dependent variable and protein binding and partition coefficient (a measure of lipophilicity) as explanatory variables. RESULTS: Four hundred eighty samples were analysed. There was no significant loss of any study drugs in the controls over 24 hours. The average drug recoveries from the ECMO circuits at 24 hours were as follows: ciprofloxacin 96%, linezolid 91%, fluconazole 91%, ceftriaxone 80%, caspofungin 56% and thiopentone 12%. There was a significant reduction of ceftriaxone (P = 0.01), caspofungin (P = 0.01) and thiopentone (P = 0.008) concentrations in the ECMO circuit at 24 hours. Both protein binding and partition coefficient were highly significant, with the model possessing a high coefficient of determination (R (2) = 0.88, P <0.001). CONCLUSIONS: Recovery of the highly protein-bound drugs ceftriaxone, caspofungin and thiopentone was significantly lower in the ECMO circuits at 24 hours. For drugs with similar lipophilicity, the extent of protein binding may determine circuit drug loss. Future clinical population pharmacokinetic studies should initially be focused on drugs with greater lipophilicity and protein binding, and therapeutic drug monitoring should be strongly considered with the use of such drugs.

The use of tracheostomy speaking valves in mechanically ventilated patients results in improved communication and does not prolong ventilation time in cardiothoracic intensive care unit patients.

PURPOSE: The aim of this study was to assess the effect of the introduction of in-line tracheostomy speaking valves (SVs) on duration of mechanical ventilation and time to verbal communication in patients requiring tracheostomy for prolonged mechanical ventilation in a predominantly cardiothoracic intensive care unit (ICU). MATERIALS AND METHODS: We performed a retrospective preobservational-postobservational study using data from the ICU clinical information system and medical record. Extracted data included demographics, diagnoses and disease severity, mechanical ventilation requirements, and details on verbal communication and oral intake. RESULTS: Data were collected on 129 patients. Mean age was 59 ± 16 years, with 75% male. Demographics, case mix, and median time from intubation to tracheostomy (6 days preimplementation-postimplementation) were unchanged between timepoints. A significant decrease in time from tracheostomy to establishing verbal communication was observed (18 days preimplementation and 9 days postimplementation, P <.05). There was no difference in length of mechanical ventilation (20 days preimplementation-post) or time to decannulation (14 days preimplementation-postimplementation). No adverse events were documented in relation to the introduction of in-line SVs. CONCLUSIONS: In-line SVs were successfully implemented in mechanically ventilated tracheostomized patient population. This resulted in earlier verbal communication, no detrimental effect on ventilator weaning times, and no change in decannulation times. PURPOSE: The purpose of the study was to compare tracheostomy outcomes in mechanically ventilated patients in a cardiothoracic ICU preintroduction and postintroduction of in-line SVs. It was hypothesized that in-line SVs would improve communication and swallowing specific outcomes with no increase in average time to decannulation or the number of adverse events.

Acute Risk Change for Cardiothoracic Admissions to Intensive Care (ARCTIC index): a new measure of quality in cardiac surgery.

BACKGROUND: Quality of cardiac surgical care may vary between institutions. Mortality is low and large numbers are required to discriminate between hospitals. Measures other than mortality may provide better comparisons. OBJECTIVES: To develop and assess the Acute Risk Change for Cardiothoracic Admissions to Intensive Care (ARCTIC) index, a new performance measure for cardiothoracic admissions to intensive care units (ICUs). METHODS: The Australian and New Zealand Society of Cardiac and Thoracic Surgeons database and Australian and New Zealand Intensive Care Society Adult Patient Database were linked. Logistic regression was used to generate a predicted risk of death first from preoperative data using the previously validated Allprocscore and second on admission to an ICU using Acute Physiology and Chronic Health Evaluation III score. Change in risk as a percentage (ARCTIC) was calculated for each patient. The validity of ARCTIC as a marker of quality was assessed by comparison with intraoperative variables and postoperative morbidity markers. RESULTS: Sixteen thousand six hundred eighty-seven patients at 21 hospitals from 2008 to 2011 were matched. An increase in ARCTIC score was associated with prolonged cardiopulmonary bypass time (P = .001), intraoperative blood product transfusion (P < .001), reoperation (P < .0001), postoperative renal failure (P < .0001), prolonged ventilation (P < .0001), and stroke (P = .001). CONCLUSIONS: The ARCTIC index is associated with known markers of perioperative performance and postoperative morbidity. It may be used as an overall marker of quality for cardiac surgery. Further work is required to assess ARCTIC as a method to discriminate between cardiac surgical units.

Extracorporeal life support devices and strategies for management of acute cardiorespiratory failure in adult patients: a comprehensive review.

Evolution of extracorporeal life support (ECLS) technology has added a new dimension to the intensive care management of acute cardiac and/or respiratory failure in adult patients who fail conventional treatment. ECLS also complements cardiac surgical and cardiology procedures, implantation of long-term mechanical cardiac assist devices, heart and lung transplantation and cardiopulmonary resuscitation. Available ECLS therapies provide a range of options to the multidisciplinary teams who are involved in the time-critical care of these complex patients. While venovenous extracorporeal membrane oxygenation (ECMO) can provide complete respiratory support, extracorporeal carbon dioxide removal facilitates protective lung ventilation and provides only partial respiratory support. Mechanical circulatory support with venoarterial (VA) ECMO employed in a traditional central/peripheral fashion or in a temporary ventricular assist device configuration may stabilise patients with decompensated cardiac failure who have evidence of end-organ dysfunction, allowing time for recovery, decision-making, and bridging to implantation of a long-term mechanical circulatory support device and occasionally heart transplantation. In highly selected patients with combined severe cardiac and respiratory failure, advanced ECLS can be provided with central VA ECMO, peripheral VA ECMO with timely transition to venovenous ECMO or VA-venous ECMO upon myocardial recovery to avoid upper body hypoxia or by addition of an oxygenator to the temporary ventricular assist device circuit. This article summarises the available ECLS options and provides insights into the principles and practice of these techniques. One should emphasise that, as is common with many emerging therapies, their optimal use is currently not backed by quality evidence. This deficiency needs to be addressed to ensure that the full potential of ECLS can be achieved.

Routine angiography in survivors of out of hospital cardiac arrest with return of spontaneous circulation: a single site registry.

BACKGROUND: Coronary revascularization in resuscitated out of hospital cardiac arrest (OOHCA) patients has been associated with improved survival. METHODS: This was a retrospective review of patients with OOHCA between 01/07/2007 and 31/03/2009 surviving to hospital admission. Cardiac risk factors, demographics, treatment times, electrocardiogram (ECG), angiographic findings and in-hospital outcomes were recorded. RESULTS: Of the 78 patients, 63 underwent coronary angiography. Traditional cardiac risk factors were common in this group. Chest pain occurred in 33.3% pre-arrest, 59.0% were initially treated at a peripheral hospital, 83.3% had documented ventricular tachycardia or ventricular fibrillation, 55.1% had specific ECG changes, 65.4% had acute myocardial infarction (AMI) as the cause of OOHCA and the majority had multi-vessel disease. ST elevation strongly predicted AMI. The in-hospital survival was 67.9% with neurological deficit in 13.2% of survivors. The group of patients who had an angiogram were more likely to have AMI as a cause of cardiac arrest (71.4% vs 40.0%, p = 0.01) and more likely to have survived to discharge (74.6% vs 40.0%, p < 0.01). Poor outcome was associated with older age, cardiogenic shock, longer transfer times, diabetes, renal impairment and a long duration to return of spontaneous circulation. CONCLUSIONS: Acute myocardial infarction was the commonest cause of OOHCA and a high rate of survival to discharge was seen with a strategy of routine angiography and revascularization.

The combined effects of extracorporeal membrane oxygenation and renal replacement therapy on meropenem pharmacokinetics: a matched cohort study.

INTRODUCTION: The scope of extracorporeal membrane oxygenation (ECMO) is expanding; however, optimal drug prescription during ECMO remains a developing science. Currently, there are no clear guidelines for antibiotic dosing during ECMO. This open-label, descriptive, matched-cohort pharmacokinetics (PK) study aimed to compare the PK of meropenem in ECMO patients to critically ill patients with sepsis not receiving ECMO (controls). METHODS: Eleven adult patients on ECMO (venovenous (VV) ECMO, n = 6; venoarterial (VA) ECMO, n = 5) receiving intravenous (IV) meropenem were included. Meropenem plasma concentrations were determined using validated chromatography. Population PK analysis was performed using non-linear mixed effects modelling. This data was compared with previously published meropenem PK data from 10 critically ill adult patients not on ECMO (preserved renal function (n = 5) or receiving renal replacement therapy (RRT) (n = 5). Using these data, we then performed Monte Carlo simulations (n = 1,000) to describe the effect of creatinine clearance on meropenem plasma concentrations. RESULTS: In total, five (two VV, three VA) out of eleven ECMO patients received RRT. The other six patients (four VV, two VA) had no significant impairment in renal function. A two-compartment model adequately described the data. ECMO patients had numerically higher volume of distribution (0.45 ± 0.17 versus 0.41 ± 0.13 L/kg, P = 0.21) and lower clearance compared to controls (7.9 ± 5.9 versus 11.7 ± 6.5 L/h, P = 0.18). Variability in meropenem clearance was correlated with creatinine clearance or the presence of RRT. The observed median trough concentrations in the controls were 4.2 (0.0 to 5.7) mg/L. In ECMO patients, while trough meropenem concentrations >2 mg/L were achieved in all patients, a more aggressive target of >8 mg/L for less susceptible microorganisms was observed in only eight out of eleven patients, with five of them being on RRT. CONCLUSIONS: ECMO patients exhibit high PK variability. Decreased meropenem CL on ECMO appears to compensate for ECMO and critical illness-related increases in volume of distribution. Routine target concentrations >2 mg/L are maintained with standard dosing (1 g IV 8-hourly). However, an increase in dose may be necessary when targeting higher concentrations or in patients with elevated creatinine clearance.

To ventilate, oscillate, or cannulate?

Ventilatory management of acute respiratory distress syndrome has evolved significantly in the last few decades. The aims have shifted from optimal gas transfer without concern for iatrogenic risks to adequate gas transfer while minimizing lung injury. This change in focus, along with improved ventilator and multiorgan system management, has resulted in a significant improvement in patient outcomes. Despite this, a number of patients develop hypoxemic respiratory failure refractory to lung-protective ventilation (LPV). The intensivist then faces the dilemma of either persisting with LPV using adjuncts (neuromuscular blocking agents, prone positioning, recruitment maneuvers, inhaled nitric oxide, inhaled prostacyclin, steroids, and surfactant) or making a transition to rescue therapies such as high-frequency oscillatory ventilation (HFOV) and/or extracorporeal membrane oxygenation (ECMO) when both these modalities are at their disposal. The lack of quality evidence and potential harm reported in recent studies question the use of HFOV as a routine rescue option. Based on current literature, the role for venovenous (VV) ECMO is probably sequential as a salvage therapy to ensure ultraprotective ventilation in selected young patients with potentially reversible respiratory failure who fail LPV despite neuromuscular paralysis and prone ventilation. Given the risk profile and the economic impact, future research should identify the patients who benefit most from VV ECMO. These choices may be further influenced by the emerging novel extracorporeal carbon dioxide removal devices that can compliment LPV. Given the heterogeneity of acute respiratory distress syndrome, each of these modalities may play a role in an individual patient. Future studies comparing LPV, HFOV, and VV ECMO should not only focus on defining the patients who benefit most from each of these therapies but also consider long-term functional outcomes.

Effect of preoperative renal function on long-term survival after cardiac surgery.

OBJECTIVES: The study objective was to investigate the effect of renal failure on intermediate-term survival in cardiac surgery patients. METHODS: All patients aged 18 years or older undergoing coronary artery bypass grafting, valvular surgery, thoracic aortic surgery, or a combination of these from January 1, 2002 to December 1, 2005 were included. Data were obtained from the cardiac surgery and intensive care databases. Using a matching algorithm, the date of death was obtained from the National Death Index. The simplified Medical Diet for Renal Disease formula was used to calculate the estimated glomerular filtration rate, and the patients were stratified accordingly. An estimation of the effect of the preoperative renal function on the interval to death was determined using Cox regression analysis with and without cubic splines and polynomial regression. The long-term survival was described using the Kaplan-Meier product limit method. RESULTS: A total of 5297 patients were included in the present study. The vital status of all patients was obtained at a mean of 2.9 years (range, 1-5) postoperatively. The actuarial 1-year survival rate was 96% ± 1%, and the 3-year survival rate was 92% ± 1%. The greatest early mortality occurred in the severe renal dysfunction group; however, the dialysis-dependent renal failure group showed increased mortality over time compared with the other groups. The lowest risk of death (longest interval to death) occurred with an estimated glomerular filtration rate of approximately 90 mL/min/1.73 m(2). CONCLUSIONS: The results of our study have shown that preoperative renal dysfunction is an independent predictor of long-term mortality in cardiac surgery patients.

An Australian tertiary referral center experience of the management of chronic thromboembolic pulmonary hypertension.

The objective of this study was to report the outcome of pulmonary endarterectomy (PEA) surgery performed for chronic thromboembolic pulmonary hypertension (CTEPH) at a single tertiary center. The prospective study consisted of 35 patients with surgically amenable CTEPH undergoing PEA between September 2004 and September 2010. The main outcome measures were Functional (New York Heart Association [NYHA] class, 6-Minute Walk Distance), hemodynamic (echocardiography, right heart catheterization, and cardiac MRI), and outcome data (morbidity and mortality). Following PEA, there were significant improvements in NYHA class (pre 2.9±0.7 vs. post 1.3±0.5, P < 0.0001), right ventricular systolic pressure (pre 77.4±24.8 mmHg vs. post 45.1±24.9 mmHg, P = 0.0005), 6-Minute Walk Distance (pre 419.6±109.4 m vs. post 521.6±83.5 m, P = 0.0017), mean pulmonary artery pressure (pre 41.8±15.3 mmHg vs. post 24.7±8.8 mmHg, P = 0.0006), and cardiac MRI indices (end diastolic volume pre 213.8±49.2 mL vs. post 148.1±34.5 mL, P < 0.0001; ejection fraction pre 40.7±9.8 mL vs. post 48.1±8.9 mL, P = 0.0069). The mean cardiopulmonary bypass time was 258.77±26.16 min, with a mean circulatory arrest time of 43.83±28.78 min, a mean ventilation time of 4.7±7.93 days (range 0.2-32.7), and a mean intensive care unit stay of 7.22±8.71 days (range 1.1-33.8). Complications included reperfusion lung injury (20%), persistent pulmonary hypertension (17.1%), slow respiratory wean (25.7%), pericardial effusion (11.4%), and cardiac tamponade (5.7%). 1-year mortality post-procedure was 11.4%. Pulmonary endarterectomy can be performed safely with relatively low mortality.

ASAP ECMO: Antibiotic, Sedative and Analgesic Pharmacokinetics during Extracorporeal Membrane Oxygenation: a multi-centre study to optimise drug therapy during ECMO.

BACKGROUND: Given the expanding scope of extracorporeal membrane oxygenation (ECMO) and its variable impact on drug pharmacokinetics as observed in neonatal studies, it is imperative that the effects of the device on the drugs commonly prescribed in the intensive care unit (ICU) are further investigated. Currently, there are no data to confirm the appropriateness of standard drug dosing in adult patients on ECMO. Ineffective drug regimens in these critically ill patients can seriously worsen patient outcomes. This study was designed to describe the pharmacokinetics of the commonly used antibiotic, analgesic and sedative drugs in adult patients receiving ECMO. METHODS/DESIGN: This is a multi-centre, open-label, descriptive pharmacokinetic (PK) study. Eligible patients will be adults treated with ECMO for severe cardiac and/or respiratory failure at five Intensive Care Units in Australia and New Zealand. Patients will receive the study drugs as part of their routine management. Blood samples will be taken from indwelling catheters to investigate plasma concentrations of several antibiotics (ceftriaxone, meropenem, vancomycin, ciprofloxacin, gentamicin, piperacillin-tazobactum, ticarcillin-clavulunate, linezolid, fluconazole, voriconazole, caspofungin, oseltamivir), sedatives and analgesics (midazolam, morphine, fentanyl, propofol, dexmedetomidine, thiopentone). The PK of each drug will be characterised to determine the variability of PK in these patients and to develop dosing guidelines for prescription during ECMO. DISCUSSION: The evidence-based dosing algorithms generated from this analysis can be evaluated in later clinical studies. This knowledge is vitally important for optimising pharmacotherapy in these most severely ill patients to maximise the opportunity for therapeutic success and minimise the risk of therapeutic failure. TRIAL REGISTRATION: ACTRN12612000559819.

Sequestration of drugs in the circuit may lead to therapeutic failure during extracorporeal membrane oxygenation.

INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) is a supportive therapy, with its success dependent on effective drug therapy that reverses the pathology and/or normalizes physiology. However, the circuit that sustains life can also sequester life-saving drugs, thereby compromising the role of ECMO as a temporary support device. This ex vivo study was designed to determine the degree of sequestration of commonly used antibiotics, sedatives and analgesics in ECMO circuits. METHODS: Four identical ECMO circuits were set up as per the standard protocol for adult patients on ECMO. The circuits were primed with crystalloid and albumin, followed by fresh human whole blood, and were maintained at a physiological pH and temperature for 24 hours. After baseline sampling, fentanyl, morphine, midazolam, meropenem and vancomycin were injected into the circuit at therapeutic concentrations. Equivalent doses of these drugs were also injected into four polyvinylchloride jars containing fresh human whole blood for drug stability testing. Serial blood samples were collected from the ECMO circuits and the controls over 24 hours and the concentrations of the study drugs were quantified using validated assays. RESULTS: Four hundred samples were analyzed. All study drugs, except meropenem, were chemically stable. The average drug recoveries from the ECMO circuits and the controls at 24 hours relative to baseline, respectively, were fentanyl 3% and 82%, morphine 103% and 97%, midazolam 13% and 100%, meropenem 20% and 42%, vancomycin 90% and 99%. There was a significant loss of fentanyl (p = 0.0005), midazolam (p = 0.01) and meropenem (p = 0.006) in the ECMO circuit at 24 hours. There was no significant circuit loss of vancomycin at 24 hours (p = 0.26). CONCLUSIONS: Sequestration of drugs in the circuit has implications on both the choice and dosing of some drugs prescribed during ECMO. Sequestration of lipophilic drugs such as fentanyl and midazolam appears significant and may in part explain the increased dosing requirements of these drugs during ECMO. Meropenem sequestration is also problematic and these data support a more frequent administration during ECMO.