Donation after circulatory death: a national survey of current practice in England in 2012.

OBJECTIVE: In recent years, England has seen renewed interest in donation after circulatory death. Many national and local initiatives have been implemented to encourage and support donation after circulatory death. To assess whether practice is in line with published guidance, we conducted a national survey with regard to current donation after circulatory death practices, local guidelines, and views on the need to further develop a national standardized protocol for donation after circulatory death. DESIGN: Online survey. SUBJECTS: Lead physicians for intensive care or organ donation for every acute National Health Service trust in England delivering adult care between April and June 2012. INTERVENTIONS: Physicians were e-mailed a link to a structured online questionnaire regarding their experience and practice of donation after circulatory death, including local protocols, use of organ optimization, and the need for a national protocol. MEASUREMENTS AND MAIN RESULTS: We received replies from 119 of 156 eligible trusts (76.3%) in England. Of these, 112 trusts (94%) have performed donation after circulatory death. Ninety-three trusts (78.1%) have a local donation after circulatory death protocol, and 89 trusts (74.7%) felt there should be a national donation after circulatory death protocol. All responding transplant centers had performed donation after circulatory death, 14 of 17 (82.3%) had a donation after circulatory death protocol with 14 of 17 respondents (82.3%) supporting a national protocol. Regarding organ optimization, 92 institutions (77.3%) used vasoactive drugs to achieve a target mean arterial blood pressure with 82 centers (68.9%) employing positive end-expiratory pressure and FIO2 to optimize oxygenation. Eight centers (6.7%) used heparin premortem compared with two of 17 transplant centers (11.8%). Two centers have used phentolamine to facilitate organ retrieval, with another five centers (4.2%) cannulating vessels premortem. CONCLUSIONS: Our survey revealed varying approaches and views toward donation after circulatory death across England. A greater than expected percentage use premortem cannulation, heparinization, and phentolamine despite current guidance in England to the contrary. The majority of institutions practicing donation after circulatory death with protocols in place favor the development of national guidelines, particularly with respect to organ optimization. We believe that such a protocol would help to address potential barriers to donation after circulatory death, which may lead to increased donation rates and improved outcomes.

Echocardiographic predictors of outcome in eisenmenger syndrome.

BACKGROUND: Eisenmenger syndrome differs significantly from other types of pulmonary arterial hypertension in its physiology and prognosis. We sought to assess the relationship between the echocardiographic characteristics of patients with Eisenmenger syndrome and mortality. METHODS AND RESULTS: Clinical and echocardiographic variables were assessed in 181 consecutive patients with Eisenmenger syndrome, excluding those with complex congenital heart disease. Patients' mean age was 39.1 ± 12.8 years, 59 (32.6%) were male, 122 (67.4%) were in functional class III or higher, and 74 (40.9%) were on advanced therapies. Mean oxygen saturation at rest was 85.1 ± 7.8%, and median B-type natriuretic peptide was 55.4 ng/L. Over a median follow-up of 16.4 months, 19 patients died; the strongest predictors of mortality were tricuspid annular plane systolic excursion and peak systolic velocity, myocardial performance (expressed as total isovolumic time and ratio of systolic to diastolic duration), and elevated central venous pressure (expressed as right atrial [RA] area, RA pressure, and ratio of RA to left atrial area), even after we accounted for advanced therapies. A composite score based on the strongest echocardiographic predictors of outcome, including 1 point for each of the following: tricuspid annular plane systolic excursion <15 mm, ratio of right ventricular effective systolic to diastolic duration ≥ 1.5, RA area ≥ 25 cm², ratio of RA to left atrial area ≥ 1.5, was highly predictive of clinical outcome (area under the curve 0.90 ± 0.01), with no improvement when B-type natriuretic peptide and resting saturations were added into the model. CONCLUSIONS: Echocardiographic parameters of right ventricular function and RA area predict mortality in Eisenmenger patients. A new composite echocardiographic score, described herewith, may be incorporated into the noninvasive, periodic assessment of these patients.

Pathophysiology of pulmonary hypertension in acute lung injury.

Acute lung injury (ALI) and acute respiratory distress syndrome are characterized by protein rich alveolar edema, reduced lung compliance, and acute severe hypoxemia. A degree of pulmonary hypertension (PH) is also characteristic, higher levels of which are associated with increased morbidity and mortality. The increase in right ventricular (RV) afterload causes RV dysfunction and failure in some patients, with associated adverse effects on oxygen delivery. Although the introduction of lung protective ventilation strategies has probably reduced the severity of PH in ALI, a recent invasive hemodynamic analysis suggests that even in the modern era, its presence remains clinically important. We therefore sought to summarize current knowledge of the pathophysiology of PH in ALI.

Pulmonary vascular and right ventricular dysfunction in adult critical care: current and emerging options for management: a systematic literature review.

INTRODUCTION: Pulmonary vascular dysfunction, pulmonary hypertension (PH), and resulting right ventricular (RV) failure occur in many critical illnesses and may be associated with a worse prognosis. PH and RV failure may be difficult to manage: principles include maintenance of appropriate RV preload, augmentation of RV function, and reduction of RV afterload by lowering pulmonary vascular resistance (PVR). We therefore provide a detailed update on the management of PH and RV failure in adult critical care. METHODS: A systematic review was performed, based on a search of the literature from 1980 to 2010, by using prespecified search terms. Relevant studies were subjected to analysis based on the GRADE method. RESULTS: Clinical studies of intensive care management of pulmonary vascular dysfunction were identified, describing volume therapy, vasopressors, sympathetic inotropes, inodilators, levosimendan, pulmonary vasodilators, and mechanical devices. The following GRADE recommendations (evidence level) are made in patients with pulmonary vascular dysfunction: 1) A weak recommendation (very-low-quality evidence) is made that close monitoring of the RV is advised as volume loading may worsen RV performance; 2) A weak recommendation (low-quality evidence) is made that low-dose norepinephrine is an effective pressor in these patients; and that 3) low-dose vasopressin may be useful to manage patients with resistant vasodilatory shock. 4) A weak recommendation (low-moderate quality evidence) is made that low-dose dobutamine improves RV function in pulmonary vascular dysfunction. 5) A strong recommendation (moderate-quality evidence) is made that phosphodiesterase type III inhibitors reduce PVR and improve RV function, although hypotension is frequent. 6) A weak recommendation (low-quality evidence) is made that levosimendan may be useful for short-term improvements in RV performance. 7) A strong recommendation (moderate-quality evidence) is made that pulmonary vasodilators reduce PVR and improve RV function, notably in pulmonary vascular dysfunction after cardiac surgery, and that the side-effect profile is reduced by using inhaled rather than systemic agents. 8) A weak recommendation (very-low-quality evidence) is made that mechanical therapies may be useful rescue therapies in some settings of pulmonary vascular dysfunction awaiting definitive therapy. CONCLUSIONS: This systematic review highlights that although some recommendations can be made to guide the critical care management of pulmonary vascular and right ventricular dysfunction, within the limitations of this review and the GRADE methodology, the quality of the evidence base is generally low, and further high-quality research is needed.

Physiological differences between various types of Eisenmenger syndrome and relation to outcome.

BACKGROUND: Eisenmenger syndrome (ES) is the most advanced form of pulmonary arterial hypertension (PAH) related to congenital heart disease. Several studies have suggested that the presence and location of the shunt defines the natural history of these patients by influencing right ventricular adaptation to PAH. We aimed to echocardiographically assess differences in cardiac physiology and outcome between various types of ES. METHODS AND RESULTS: In this longitudinal cohort study, 191 patients with ES and non-complex congenital heart disease were recruited, 36 with pre-tricuspid and 155 with post-tricuspid shunts. Patients with pre-tricuspid shunts were older, had higher BNP concentrations and lower exercise tolerance compared to patients with post-tricuspid shunts. Right ventricular (RV) function was impaired in patients with atrial septal defects, with larger right ventricles, impaired systolic function and adaptation. The left ventricular eccentricity index was significantly higher in pre-tricuspid defects. Within post-tricuspid shunts, patients with atrio-ventricular septal defects had better right ventricular function compared to ventricular septal defects, while in those with a patent ductus arteriosus this was worse. There was a trend towards lower mortality in patients with post versus pre-tricuspid shunts, which was significant for patients above the age of 48 years. CONCLUSION: The presence of a post-tricuspid shunt appears to carry physiological and possibly prognostic benefits in ES compared to patients with pre-tricuspid shunts. This should be borne in mind when management decisions and advanced therapies are considered.

Treatment of sarcoidosis-associated pulmonary hypertension: A single centre retrospective experience using targeted therapies.

BACKGROUND: Pulmonary hypertension (PH), an increasingly recognised complication of pulmonary sarcoidosis, is associated with increased morbidity and mortality Evidence of benefit with targeted therapies in sarcoidosis associated pulmonary hypertension (SAPH) is limited. METHODS: We conducted a retrospective review of patients with sarcoidosis and right heart catheter proven PH who received treatment with targeted therapies (phosphodiesterase-5 inhibitors, endothelin receptor antagonists, or combination) at our hospital. Six minute walk test (6MWT), World Health Organisation (WHO) functional class, echocardiography, pulmonary function test (PFT) and serum brain natriuretic peptide (BNP) data were collected at baseline and during follow-up. RESULTS: Thirty-three patients (16 men) with a mean age of 55.5 ± 10.7 years and mean pulmonary artery pressure of 44.0 ± 8.6 mm Hg received treatment with targeted PH therapies (sildenafil=29, bosentan=4). At six months, median six minute walk distance improved from 227 (88-526) meters to 240 (140-380) metres (p=0.04), median serum BNP levels improved from 35 (2-424) pmol/L to 26 (4-255) pmol/L (p<0.01), and at echocardiography, median tricuspid annular plane systolic excursion (TAPSE) improved from 17.5 (8.0-27.0) mm to 20.0 (15.0-27.0) mm (p=0.03). WHO functional class improved in 14 patients. Two patients developed side-effects attributed to sildenafil (n=1) or bosentan (n=1), requiring conversion to alternative PH therapies. Ten patients died, and one patient underwent lung transplantation, a median of 13.5 (3-37) months after commencing targeted therapies. CONCLUSIONS: Our results suggest that targeted therapies are safe in patients with SAPH. Controlled trials are warranted before therapeutic recommendations can be made.

Disease targeting therapies in patients with Eisenmenger syndrome: response to treatment and long-term efficiency.

OBJECTIVES: To examine long-term efficacy of disease targeting therapies (DTT) in patients with Eisenmenger syndrome. METHODS: All adult patients with Eisenmenger syndrome treated with DTT at our institution were included. Functional class (FC), oxygen saturation and 6-minute walk test distance (6 MWTd) were analysed retrospectively. RESULTS: Between 2002 and 2010, 79 Eisenmenger patients (21 males, 16 with Down syndrome) aged 34 ± 10 years (range 17-68 years) were included. Median follow-up was 3.3 years (range 0.2 to 8.9 years). 6 MWTd increased early after initiation of DTT, with a plateau after approximately 3 years and no obvious trend towards a deterioration on average during longer-term follow-up. Two patients died during follow-up and escalation of treatment was required in 18 patients after a median period of 2.5 years. Escalation of therapy was also associated with an increase in 6 MWTd. In addition, FC improved on DTT and oxygen saturation, increased, both at rest and peak exercise. This effect was more pronounced in the patients with the lowest baseline oxygen saturation at rest. CONCLUSIONS: Long-term DTT is safe and improves objective exercise capacity and subjective symptoms. Response to DTT was typically observed early after initiation of DTT and was, on average, maintained longer-term. However, 1 in 5 patients required escalation of DTT, with time, due to symptomatic deterioration and this was associated with an afresh improvement in 6 MWTd.