Association between body composition and mortality in patients requiring extracorporeal membrane oxygenation support.

AIM: To ascertain the association between body composition, including muscle mass and adiposity, and patient mortality in those requiring extracorporeal membrane oxygenation (ECMO) for acute respiratory failure. MATERIALS AND METHODS: A retrospective study was undertaken of all patients with acute respiratory failure requiring veno-venous (VV) ECMO between January 2015 and December 2019. Automated image segmentation software was used to quantify the cross-sectional area and average radiodensity (in Hounsfield units) of different muscle and fat compartments at the L3 level of whole-body computed tomography (CT) images taken within 48 h of initiation of ECMO support. The primary endpoint was 30-day post-ECMO initiation all-cause mortality. Logistic regression was used to analyse the correlation between CT measurements, co-morbidities, and 30-day survival. RESULTS: The study included 189 patients (age = 43.8 ± 14.6, sex = 42.3% female). There was no significant association between 30-day survival status and cross-sectional area of muscle or fat. Muscle attenuation (psoas, long spine, and abdominal muscles respectively) at the L3 level were significantly lower in those who died within 30 days of ECMO cannulation (p<0.05). On multivariable analysis including age, sex, and pre-existing respiratory comorbidities, psoas muscle attenuation was an independent predictor of survival at 30 days (OR 0.97; 95% CI 0.94 to 1.00; p=0.047). CONCLUSIONS: Reduced psoas muscle attenuation is associated with poorer survival outcomes at 30 days post-ECMO cannulation in patients who received VV ECMO support for respiratory failure. Cross-sectional areas of muscle and fat compartments did not correlate with survival outcomes at 30 days even when corrected for height and sex.

Routine whole-body CT identifies clinically significant findings in patients supported with veno-venous extracorporeal membrane oxygenation.

AIM: To determine the yield of routine whole-body computed tomography (CT) following extracorporeal membrane oxygenation (ECMO) initiation and to assess the association of these findings with prognosis. MATERIALS AND METHODS: One hundred and ninety-eight consecutive patients with acute respiratory failure admitted for ECMO support between January 2015 and December 2019 who underwent whole-body CT performed within 48 h of ECMO initiation were examined in this single-institution retrospective study. CT findings were divided into three categories: clinically significant findings that may affect immediate management strategy or short-term outcomes; findings not related to hospital stay or outcome but require further workup; and benign findings that do not require further investigation. Logistic regression analysis was used to assess the association of CT findings with 7- and 30-day survival. RESULTS: Clinically significant findings were present in 147 (74%) patients, findings requiring further workup were found in 82 (41%) patients, and benign findings were identified in 180 (90%) of the patients. Patients with clinically significant neurological findings had an elevated risk of death at 7 days (odds ratio [OR] 3.58; 95% confidence interval [CI] 1.29; 9.93; p=0.01), but not 30 days. Increasing numbers of clinically significant findings were associated with greater odds of mortality at 7 days (OR 1.70; 95% CI 1.08; 2.67; p=0.02) and 30 days (OR 1.41; 95% CI 1.02; 1.96; p=0.04). CONCLUSIONS: Imaging patients at the point of admission for VV-ECMO with CT frequently identified clinically significant abnormalities with prognostic implications of these. These findings provide support for the use of more routine CT at the point of treatment escalation with prospective studies now required.

Extracorporeal membrane oxygenation in acute massive pulmonary embolism: a systematic review.

Massive pulmonary embolism (PE) can present with extreme physiological dysfunction, characterised by acute right ventricular failure, hypoxaemia unresponsive to conventional therapy and cardiac arrest. Consensus regarding the management of patients with persistent shock following thrombolysis is lacking. Our primary objective was to describe the application of extracorporeal membrane oxygenation (ECMO) in the treatment of acute massive PE. We were unable to identify any randomised controlled trials (RCTs) comparing ECMO with other support systems in the setting of massive PE. We reviewed case reports and case series published in the past 20 years to evaluate the mortality rate and any poor prognostic factors. Overall survival was 70.1% and none of the definitive treatment modalities was associated with a higher mortality (thrombolysis - OR - 0.99, P - 0.9, catheter embolectomy - OR - 1.01, P - 0.99, surgical embolectomy - OR - 0.44, P - 0.20). Patients who had ECMO instituted whilst in cardiorespiratory arrest had a higher risk of death. (OR - 16.71, P - 0.0004). When compared with other causes of cardiac arrest, patients who survived a massive PE presented a good neurological outcome (cerebral performance category 1 or 2).

ECMO cannula review.

This paper reviews the basic fluid dynamics underlying extracorporeal membrane oxygenation (ECMO) cannula design. General cannula features and their effect on flow are discussed and the specific requirements of different ECMO circuits are explained. The current commercially available cannula options for veno-arterial and veno-venous circuits are reviewed and the main characteristics presented.

The impact of computerised physician order entry on prescribing practices in a cardiothoracic intensive care unit.

This prospective, time series, cross-sectional study was designed to compare the quality of handwritten vs computerised prescriptions in a tertiary 25-bedded cardiothoracic intensive care unit. A total of 14,721 prescriptions for 613 patients were analysed over three periods of investigation: 7 months before; and 5 and 12 months after implementation of a clinical information system with computerised physician order entry capability. Errors in prescribing were common. Only (53%) of handwritten charts analysed had all immediate administration drugs prescribed correctly. Errors included omission of route 81 (8.0%), date of prescription 78 (7.7%), and time to be given 255 (25.2%), and 119 (11.7%) had no dose or an incorrect dose prescribed. All errors of completeness were abolished following implementation. The computerised system led to a significant improvement in prescribing safety, in a clinical area previously highlighted as having a high rate of adverse drug errors. Legibility, completeness and traceability are no longer possible sources of medication errors.

Survival and length of stay following blood transfusion in octogenarians following cardiac surgery.

Our aim was to assess if peri-operative blood transfusion is an independent risk factor for mortality and morbidity in the elderly. We report the results of a cohort study of all patients aged 80 or more on the day of their emergency or elective cardiac surgery (n = 874), using routinely collected data from January 2003 to November 2007. The primary outcome was all-cause mortality in hospital. The secondary outcomes were duration of stay in the intensive care unit (ICU) and overall hospital stay. Confounding variables were used to build up a risk model using a multivariable logistic regression analysis, and blood transfusion was added to assess whether it had additional predictive value for hospital mortality. Patients were divided into three groups: (i) transfusion of 0-2 units of red blood cells; (ii) transfusion of > 2 units of red blood cells and (iii) transfusion of red blood cells plus other clotting products. The strongest independent predictors of hospital death were logistic EuroSCORE and body mass index. After inclusion of these two variables, the odds ratio for transfusion remained significant. Relative to 0-2 units, the odds ratio for > 2 units was 6.80 (95% CI 2.46-18.8), and for other additional blood products was 14.4 (95% CI 5.34-37.3), with a p value of < 0.001. Duration of stay in the ICU was significantly associated with the amount of blood products administered (median (IQR [range]) ICU stay 1 (1-2 [0-15]) day if transfused 0-2 units of red blood cells, 2 (1-6 [0-128]) days if transfused > 2 units of red blood cells and 3 (1-76 [0-114]) days if other clotting products were used; p value < 0.001). Hospital stay was also associated with the amount of red cells used (p < 0.001).

Diagnosis of death using neurological criteria in adult patients on extracorporeal membrane oxygenation: Development of UK guidance.

The diagnosis of death using neurological criteria is an important legal method of establishing death in the UK. The safety of the diagnosis lies in the exclusion of conditions which may mask the diagnosis and the testing of the fundamental reflexes of the brainstem including the apnoea reflex. Extracorporeal membrane oxygenation for cardiac or respiratory support can impact upon these tests, both through drug sequestration in the circuit and also through the ability to undertake the apnoea test. Until recently, there has been no nationally accepted guidance regarding the conduct of the tests to undertake the diagnosis of death using neurological criteria for a patient on extracorporeal membrane oxygenation. This article considers both the background to and the process of guideline development.

Management of an acute catecholamine-induced cardiomyopathy and circulatory collapse: a multidisciplinary approach.

A phaeochromocytoma (PC) is a rare, catecholamine-secreting neuroendocrine tumour arising from the adrenal medulla. Presenting symptoms of this rare tumour are highly variable but life-threatening multiorgan dysfunction can occur secondary to catecholamine-induced hypertension or hypotension and subsequent cardiovascular collapse. High levels of circulating catecholamines can induce an acute stress cardiomyopathy, also known as Takotsubo cardiomyopathy. Recent studies have focused on early diagnosis and estimation of the prevalence of acute stress cardiomyopathy in patients with PC, but very little is reported about management of these complex cases. Here, we report the case of a 38-year-old lady who presented with an acute Takotsubo or stress cardiomyopathy and catecholamine crisis, caused by an occult left-sided 5 cm PC. The initial presenting crisis manifested with symptoms of severe headache and abdominal pain, triggered by a respiratory tract infection. On admission to hospital, the patient rapidly deteriorated, developing respiratory failure, cardiogenic shock and subsequent cardiovascular collapse due to further exacerbation of the catecholamine crisis caused by a combination of opiates and intravenous corticosteroid. An echocardiogram revealed left ventricular apical hypokinesia and ballooning, with an estimated left ventricular ejection fraction of 10-15%. Herein, we outline the early stabilisation period, preoperative optimisation and intraoperative management, providing anecdotal guidance for the management of this rare life-threatening complication of PC. LEARNING POINTS: A diagnosis of phaeochromocytoma should be considered in patients presenting with acute cardiomyopathy or cardiogenic shock without a clear ischaemic or valvular aetiology.Catecholamine crisis is a life-threatening medical emergency that requires cross-disciplinary expertise and management to ensure the best clinical outcome.After initial resuscitation, treatment of acute catecholamine-induced stress cardiomyopathy requires careful introduction of alpha-blockade followed by beta-blockade if necessary to manage ß-receptor-mediated tachycardia.Prolonged α-adrenergic receptor stimulation by high levels of circulating catecholamines precipitates arterial vasoconstriction and intravascular volume contraction, which can further exacerbate hypotension. Invasive pressure monitoring can aid management of intravascular volume in these complex patients.

pRotective vEntilation with veno-venouS lung assisT in respiratory failure: A protocol for a multicentre randomised controlled trial of extracorporeal carbon dioxide removal in patients with acute hypoxaemic respiratory failure.

One of the few interventions to demonstrate improved outcomes for acute hypoxaemic respiratory failure is reducing tidal volumes when using mechanical ventilation, often termed lung protective ventilation. Veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R) can facilitate reducing tidal volumes. pRotective vEntilation with veno-venouS lung assisT (REST) is a randomised, allocation concealed, controlled, open, multicentre pragmatic trial to determine the clinical and cost-effectiveness of lower tidal volume mechanical ventilation facilitated by vv-ECCO2R in patients with acute hypoxaemic respiratory failure. Patients requiring intubation and mechanical ventilation for acute hypoxaemic respiratory failure will be randomly allocated to receive either vv-ECCO2R and lower tidal volume mechanical ventilation or standard care with stratification by recruitment centre. There is a need for a large randomised controlled trial to establish whether vv-ECCO2R in acute hypoxaemic respiratory failure can allow the use of a more protective lung ventilation strategy and is associated with improved patient outcomes.

A phase II dose-response study of hemoglobin raffimer (Hemolink) in elective coronary artery bypass surgery.

BACKGROUND: We performed this study to determine the dose-response of hemoglobin raffimer administered in conjunction with intraoperative autologous donation in patients undergoing coronary artery bypass grafting surgery. A secondary objective was to evaluate hemoglobin raffimer for reducing the incidence of allogeneic red blood cell transfusions. METHODS: This was a phase II, single-blind, multicenter, placebo-controlled, open-label study. Patients undergoing coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation were randomized to receive a single dose of hemoglobin raffimer or control (10% pentastarch). Patients were sequentially enrolled in a dose block of 250, 500, 750, and 1000 mL. RESULTS: Sixty patients received hemoglobin raffimer (n = 30) or control (n = 30). Hemoglobin raffimer was well tolerated. Most (98%) adverse events were mild or moderate in severity. There was an expected dose-dependent increase in the incidence of blood pressure increases and jaundice in hemoglobin raffimer-treated patients. In a dose-pooled analysis of hemoglobin raffimer versus control, increased blood pressure (43% vs 17%), nausea (37% vs 33%), and atrial fibrillation (37% vs 17%) were the most frequently reported adverse events. All serious adverse events were considered unrelated or unlikely to be related to study drug. No hemoglobin raffimer-treated patient required an intraoperative allogeneic red blood cell transfusion, compared with 5 (17%) pentastarch-treated patients (P =.052). This advantage of hemoglobin raffimer was maintained at 24 hours after surgery (7% vs 37%; P =.010) and up to 5 days after surgery (10% vs 47%; P =.0034). CONCLUSIONS: Hemoglobin raffimer was not associated with any serious adverse events in patients undergoing primary coronary artery bypass grafting with cardiopulmonary bypass and intraoperative autologous donation in a dose-response study up to 1000 mL. Hemoglobin raffimer was effective in facilitating decreased exposure or avoidance of allogeneic red blood cell transfusions when used in conjunction with intraoperative autologous donation.

Steady-state measurement of NO and CO lung diffusing capacity on moderate exercise in men.

Using a rapidly responding nitric oxide (NO) analyzer, we measured the steady-state NO diffusing capacity (DL(NO)) from end-tidal NO. The diffusing capacity of the alveolar capillary membrane and pulmonary capillary blood volume were calculated from the steady-state diffusing capacity for CO (measured simultaneously) and the specific transfer conductance of blood per milliliter for NO and for CO. Nine men were studied bicycling at an average O(2) consumption of 1.3 +/- 0.2 l/min (mean +/- SD). DL(NO) was 202.7 +/- 71.2 ml. min(-1). Torr(-1) and steady-state diffusing capacity for CO, calculated from end-tidal (assumed alveolar) CO(2), mixed expired CO(2), and mixed expired CO, was 46.9 +/- 12.8 ml. min(-1). Torr(-1). NO dead space = (VT x FE(NO) - VT x FA(NO))/(FI(NO) - FA(NO)) = 209 +/- 88 ml, where VT is tidal volume and FE(NO), FI(NO), and FA(NO) are mixed exhaled, inhaled, and alveolar NO concentrations, respectively. We used the Bohr equation to estimate CO(2) dead space from mixed exhaled and end-tidal (assumed alveolar) CO(2) = 430 +/- 136 ml. Predicted anatomic dead space = 199 +/- 22 ml. Membrane diffusing capacity was 333 and 166 ml. min(-1). Torr(-1) for NO and CO, respectively, and pulmonary capillary blood volume was 140 ml. Inhalation of repeated breaths of NO over 80 s did not alter DL(NO) at the concentrations used.

The action of diaspirin cross-linked haemoglobin blood substitute on human arterial bypass conduits.

BACKGROUND: Immediately available blood substitutes could transform medicine. In coronary artery surgery, vasoconstriction induced by some of these agents could have serious implications. We have examined some of the vasoactive effects of one of these blood substitute, diaspirin cross-linked haemoglobin (DCLHb), on isolated rings of human arterial conduits. METHODS: Sections of human left internal mammary artery (LIMA) and radial artery (RA) were cut into 3-mm rings, mounted in individual organ baths containing aerated (95% O(2)/5% CO(2)) Krebs-Heinseleit solution at 37 degrees C and attached to isometric strain gauge for measurements of tension. All rings were tested for the presence of endothelium by addition of carbachol to rings pre-contracted with phenylephrine. The relative importance of nitric oxide (NO) in contraction mediated by the addition of DCLHb was studied. RESULTS: Carbachol relaxed phenylephrine precontracted LIMA by 72.3+/-1.7% and RA by 97+/-0.7% confirming the presence of a functional endothelium. Sodium nitroprusside (SNP) caused complete relaxation of LIMA with an EC(50) value of 2.0+/-0.1x10(-8) M and RA with an EC(50) value of 1. 9+/-0.1x10(8) M. In the presence of DCLHb (10(-7) M), carbachol-induced relaxation was significantly reduced to 46.3+/-0. 7% (P<0.01) and the BC(50) value for SNP relaxation increased to 1. 2+/-0.1x10(-7) M (P<0.01). DCLHb caused rings to contract in the absence of phenylephrine with EC(50) values of 1.6+/-0.1x10(-7) M (LIMA) and 1.8+/-0.1x10(-7) M (RA). Presence of L-NAME (300 microM) caused no alteration in DCLHb-induced contraction. CONCLUSION: In this study of isolated rings of human vessels, DCLHb causes a significant reduction in relaxation mediated by carbachol and SNP, which is likely to be due to its ability to bind NO. However, it is possible that other mechanisms might contribute to the vasoconstrictor effects of DCLHb and these might be amenable to anti-vasospastic strategies.

Inhibitory effects of glibenclamide on the contraction of human arterial conduits used in coronary artery bypass surgery.

Glibenclamide has been shown to inhibit prostanoid-induced contraction in a number of blood vessel types. In this study, the effects of glibenclamide on the contraction of human peripheral arteries in response to both prostanoid and non-prostanoid agonists were compared and possible mechanisms of action were investigated. Segments of left internal mammary artery (LIMA) and radial artery, taken from patients undergoing coronary artery bypass graft (CABG) surgery, were mounted in organ baths containing physiological saline solution aerated with 95% O2/5% CO2 at 37 degrees C. Contractions were obtained by either the use of a thromboxane analogue (U46619), L-phenylephrine, KCl or CaCl2. The effects of glibenclamide on these contractions were observed and pEC50 values were determined after manipulation of a logistic curve-fitting equation. Concentration-dependent relaxation of U46619-contracted LIMA and radial artery was observed in the presence of glibenclamide, with calculated pEC50 values of 4.2+/-0.17 (n = 7) for LIMA and 3.26+/-0.48 (n = 5) for radial artery. Incubation of both LIMA and radial artery with glibenclamide (50 microM) caused the concentration-response curves for U46619 and L-phenylephrine to shift significantly to the right. Similarly the KCl tension relationship was caused to shift to the right. Finally, glibenclamide (100 microM) also had an inhibitory effect on Ca2+-induced tension in radial artery. These results show that the inhibitory effects of glibenclamide on human peripheral blood vessels are not restricted to prostanoid-induced contractions. Furthermore, evidence has been provided to suggest that these effects might be mediated through an interaction with voltage-sensitive Ca2+ channels.

[Hydrofluoric acid: an unrecognised toxic agent]. / L'acide fluorhydrique: un toxique méconnu.

Hydrofluoric acid has widespread uses in industry and at home. Its mechanism of toxicity is the basis of a specific treatment. Cutaneous burns are the most common form of toxicity and the consequences can be catastrophic. Its insidious presentation can delay any therapeutic action, except if the physician is aware about it. A case report underlines the beneficial action of the intra-arterial infusion of calcium gluconate.

Postoperative fibrinogen level is associated with postoperative bleeding following cardiothoracic surgery and the effect of fibrinogen replacement therapy remains uncertain.

BACKGROUND: Traditionally, a fibrinogen level > 1 g L(-1) has been viewed as the critical plasma concentration required for hemostasis. No definitive trial has investigated the plasma fibrinogen hemostatic threshold and fibrinogen replacement in complex surgical patients with acquired bleeding. OBJECTIVES: To explore the plasma fibrinogen level required for hemostasis in cardiothoracic surgery patients and assess the association of fibrinogen replacement therapy (using cryoprecipitate or fibrinogen concentrate) with reducing postoperative bleeding rate. PATIENTS/METHODS: Data from a prospectively collated database were used to examine the relationship between postoperative plasma fibrinogen level and the postoperative rate of bleeding within the hour of plasma fibrinogen measurement (n = 430) and to explore the effect of cryoprecipitate infusion (n = 76) or fibrinogen concentrate administration (n = 8) on postoperative bleeding rate. RESULTS: A low plasma fibrinogen level was significantly associated with bleeding, with an odds ratio of 3.06 for every 1 g L(-1) decrease in fibrinogen (95% confidence interval 1.05-8.90) with adjustment for confounders. A fibrinogen threshold associated with excess bleeding was not identified, but this relationship was a continuum. There was no reduction in bleeding following administration of cryoprecipitate or fibrinogen concentrate to raise the post-infusion fibrinogen level to a median of 2.00 and 1.70 g L(-1) , respectively. CONCLUSIONS: There is a continuum of bleeding severity with reducing fibrinogen concentration. Fibrinogen concentrate or cryoprecipitate infusion did not significantly reduce bleeding rate; however, confirmation by a randomized controlled trial is required. It remains uncertain whether low postoperative fibrinogen levels are causally associated with postoperative bleeding.

Modelling lung and tissue diffusion using a membrane oxygenator circuit.

A simple model lung has been designed using a membrane oxygenator circuit comprising two membrane oxygenators primed with one to two litres of equine blood, giving reproducible results over several hours. Normoxia and normocapnia were achieved consistently over the duration of the test with a blood flow of 2.5 l/min, oxygenator ventilation gas flow of 5 l/min air with 0.3 l/min O2 and deoxygenator ventilation gas flow of 5 l/min 5% CO2 in N2 with 0.2 l/min CO2. The measured PaO2 was 81.3 (SD 3.35 mmHg), PvO2 38.3 (SD 1.38 mmHg), PvCO2 60.6 (SD 1.13 mmHg) and PaCO2 36.1 (SD 0.69mmHg). MO2 and MCO2 were 116 ml/min and 169 ml/min, respectively. An increasing linear relationship was observed for FiO2 and the corresponding PaO2 and, similarly, with FiCO2 and PvCO2, providing reference ranges for this model.