Characteristics of ventricular tachycardia ablation in patients with continuous flow left ventricular assist devices.

BACKGROUND: Left ventricular assist devices (LVADs) are increasingly used as a bridge to cardiac transplantation or as destination therapy. Patients with LVADs are at high risk for ventricular arrhythmias. This study describes ventricular arrhythmia characteristics and ablation in patients implanted with a Heart Mate II device. METHODS AND RESULTS: All patients with a Heart Mate II device who underwent ventricular arrhythmia catheter ablation at 9 tertiary centers were included. Thirty-four patients (30 male, age 58±10 years) underwent 39 ablation procedures. The underlying cardiomyopathy pathogenesis was ischemic in 21 and nonischemic in 13 patients with a mean left ventricular ejection fraction of 17%±5% before LVAD implantation. One hundred and ten ventricular tachycardias (VTs; cycle lengths, 230-740 ms, arrhythmic storm n=28) and 2 ventricular fibrillation triggers were targeted (25 transseptal, 14 retrograde aortic approaches). Nine patients required VT ablation <1 month after LVAD implantation because of intractable VT. Only 10/110 (9%) of the targeted VTs were related to the Heart Mate II cannula. During follow-up, 7 patients were transplanted and 10 died. Of the remaining 17 patients, 13 were arrhythmia-free at 25±15 months. In 1 patient with VT recurrence, change of turbine speed from 9400 to 9000 rpm extinguished VT. CONCLUSIONS: Catheter ablation of VT among LVAD recipients is feasible and reasonably safe even soon after LVAD implantation. Intrinsic myocardial scar, rather than the apical cannula, seems to be the dominant substrate.

The use of Impella 2.5 in severe refractory cardiogenic shock complicating an acute myocardial infarction.

OBJECTIVES: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. BACKGROUND: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. METHODS: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. RESULTS: In this analysis, patients were relatively young with a mean age of 57.9 ± 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 ± 5.3 mmol/L to 2.41 ± 2.1 mmo/L, (P = 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 ± 10% vs. 27 ± 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. CONCLUSION: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome.

Assessment of platelet function with light transmission aggregometry in 24 patients supported with a continuous-flow left ventricular assist device: a single-center experience.

OBJECTIVES: This study evaluated platelet function for an extended period of time in patients with a HeartMate II continuous-flow left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) with light transmission aggregometry and investigated the potential role of this test in clinical management. METHODS: Twenty-four patients were studied prospectively after implantation. Mean duration of support was 8.5 months. Platelet functions were assessed with light transmission aggregometry induced by thrombin receptor agonist peptide, ristocetin, or arachidonic acid. All patients received an aspirin regimen that was progressively increased until arachidonic acid-triggered platelet aggregation dropped lower than 20%. Plasma levels of von Willebrand factor were also determined when ristocetin-induced platelet agglutination was impaired. RESULTS: Intensity of platelet aggregation with thrombin receptor agonist peptide was little changed in patients with a HeartMate II relative to control subjects. Aspirin dose greater than 160 mg/d was progressively required in 46% of patients. Ristocetin-induced platelet agglutination was impaired in 4 patients in association with a lack of high molecular weight von Willebrand factor multimers. Three patients had thromboembolic events (12.5%) and 8 (33%) suffered from major bleeding complications. CONCLUSIONS: High platelet reactivity during treatment with aspirin is common in patients with a HeartMate II. Moreover, light transmission aggregometry may detect impaired ristocetin-induced platelet agglutination, enabling dosage of aspirin to be adjusted. Our strategy showed no major improvements in terms of thrombosis rate when compared with published data, although bleeding frequency was somewhat reduced. Benefits of light transmission aggregometry testing need to be assessed in a larger randomized study with a longer follow-up.

Fresh-frozen plasma transfusion did not reduce 30-day mortality in patients undergoing cardiopulmonary bypass cardiac surgery with excessive bleeding: the PLASMACARD multicenter cohort study.

BACKGROUND: During on-pump cardiac surgery, hemorrhagic complications occur frequently. Fresh-frozen plasma (FFP) is widely transfused to provide coagulation factors. Yet, no randomized clinical trial has demonstrated its benefits on mortality. We assessed the relationship between therapeutic transfusion of FFP and 30-day mortality in cardiac surgery patients suffering from excessive bleeding in a prospective cohort study. STUDY DESIGN AND METHODS: Adult patients who underwent on-pump cardiac surgery and experienced excessive bleeding during the 48-hour perioperative period were recruited from 15 French centers between February 2004 and January 2006. Patients who received a preventive FFP transfusion were excluded. The association between FFP transfusion and all cause 30-day mortality was estimated using a Cox proportional hazards model, adjusted for confounding. A propensity score (PS) sensitivity analysis was also performed. RESULTS: Among 967 patients included in this study, 58.1% received FFP. The median dose was 11.3 mL/kg (interquartile range, 7.6-19.5). The cumulative 30-day mortality rate was 11.3% (95% confidence interval [CI], 9.5-13.5). FFP transfusion was associated with a higher 30-day mortality (hazard ratio [HR], 3.2; 95% CI, 1.7-6.1) in univariate analysis; however, after adjusting for prognostic factors, there was no longer any association (HR, 1.5; 95% CI, 0.8-3.0, p = 0.20). The results of the PS analysis were consistent with the adjusted analysis. CONCLUSION: Among on-pump cardiac surgery patients experiencing excessive perioperative bleeding, there is no evidence of a beneficial impact of FFP transfusion on mortality.

Predicting fluid responsiveness during infrarenal aortic cross-clamping in pigs.

OBJECTIVE: Infrarenal aortic cross-clamping (ACC) induces hemodynamic disturbances that may affect respiratory-induced variations in stroke volume and, therefore, affect the ability of dynamic parameters such as pulse-pressure variation (PPV) to predict fluid responsiveness. Since this issue has not been investigated yet to authors' knowledge, the hypothesis was tested that ACC may change PPV and impair its ability to predict fluid responsiveness. DESIGN: Prospective laboratory experiment. SETTING: A university research laboratory. PARTICIPANTS: Nineteen anesthetized and mechanically ventilated pigs. INTERVENTIONS: Two courses of volume expansion were performed using 500 mL of saline before and during ACC. Animals were monitored using a systemic arterial catheter, and a pulmonary arterial catheter (stroke volume, central venous pressure, pulmonary arterial occlusion pressure). Animals were defined as responders to volume expansion if stroke volume increased ≥ 15%. RESULTS: Before ACC, 13 animals were responders. Fluid responsiveness was predicted by a PPV ≥ 14% with a sensitivity of 77% (95% CI = 46%-95%) and a specificity of 83% (95% CI = 36%-97%). The area under the receiver operating characteristic curve was 0.90(95% CI = 0.67-0.99) and was higher than those generated for central venous pressure and pulmonary arterial occlusion pressure. ACC induced an increase in PPV (p<0.0005). During ACC, 8 animals were responders. An 18% PPV threshold discriminated between responders and non-responders to volume expansion, with a sensitivity of 87% (95% CI = 47%-98%) and a specificity of 54% (95% CI = 23%-83%). The area under the receiver operating characteristic curve was 0.72 (95% CI = 0.47-0.90) and was not different from those generated for central venous pressure and pulmonary arterial occlusion pressure. CONCLUSIONS: ACC induced a significant increase in PPV and reduced its ability to predict fluid responsiveness.

High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial.

PURPOSE: Septic shock is a leading cause of death among critically ill patients, in particular when complicated by acute kidney injury (AKI). Small experimental and human clinical studies have suggested that high-volume haemofiltration (HVHF) may improve haemodynamic profile and mortality. We sought to determine the impact of HVHF on 28-day mortality in critically ill patients with septic shock and AKI. METHODS: This was a prospective, randomized, open, multicentre clinical trial conducted at 18 intensive care units in France, Belgium and the Netherlands. A total of 140 critically ill patients with septic shock and AKI for less than 24 h were enrolled from October 2005 through March 2010. Patients were randomized to either HVHF at 70 mL/kg/h or standard-volume haemofiltration (SVHF) at 35 mL/kg/h, for a 96-h period. RESULTS: Primary endpoint was 28-day mortality. The trial was stopped prematurely after enrolment of 140 patients because of slow patient accrual and resources no longer being available. A total of 137 patients were analysed (two withdrew consent, one was excluded); 66 patients in the HVHF group and 71 in the SVHF group. Mortality at 28 days was lower than expected but not different between groups (HVHF 37.9 % vs. SVHF 40.8 %, log-rank test p = 0.94). There were no statistically significant differences in any of the secondary endpoints between treatment groups. CONCLUSIONS: In the IVOIRE trial, there was no evidence that HVHF at 70 mL/kg/h, when compared with contemporary SVHF at 35 mL/kg/h, leads to a reduction of 28-day mortality or contributes to early improvements in haemodynamic profile or organ function. HVHF, as applied in this trial, cannot be recommended for treatment of septic shock complicated by AKI.

Hypoxia-preconditioned mesenchymal stromal cells improve cardiac function in a swine model of chronic myocardial ischaemia.

OBJECTIVES: Cell loss during cardiac injection and hostility of the host-tissue microenvironment have the potential to diminish the overall effect of stem cell therapy. The purposes of this study were to evaluate the effect of a hypoxic preconditioning of mesenchymal stromal cells (MSC), to determine its safety and effectiveness, and to improve the efficacy of cell therapy using MSC in the setting of chronic myocardial ischaemia in swine. METHODS: Myocardial ischaemia was induced by an ameroid constrictor. Human MSC were cultured under normoxic (20% O2) or hypoxic conditions (1.5% O2) before transplantation. One month after ischaemia, pigs were randomly assigned to saline injection (sham), and 1 × 10(6)/kg normoxic or hypoxic MSC transplantation into the ischaemic inferior-lateral zone. RESULTS: Twenty-seven pigs were operated on and the mortality rate was 33.3%. The remaining 18 animals were randomly assigned to sham (n = 4), normoxic (n = 8) or hypoxic MSC (n = 6) treatment. Global systolic (left ventricle ejection fraction, P = 0.04) and diastolic (E/Ea, P = 0.008) functions were increased in the hypoxic group compared with other groups. The peak of 2-dimensional longitudinal strain was less altered in the hypoxic group compared with other groups (P < 0.001). Haemodynamic data showed that dP/dT max was improved in the hypoxic group compared with the other group (P < 0.01). Capillary density was increased in the hypoxic group (P = 0.001). MSC density was significantly higher in the ischaemic zone in the hypoxic group (P < 0.01). CONCLUSION: MSC engraftment with hypoxic preconditioning significantly improves capillary density and cell survival, resulting in improvement in global, regional and diastolic left ventricular functions. This highlights the therapeutic potential of transplanting hypoxic-preconditioned MSC in the setting of chronic ischaemic heart failure.

Optimization of Impella 5.0 implantation using mini-sternotomy approach in postmyocardial infarction cardiogenic shock.

The Impella Recover LP 5.0® (Abiomed, Inc. Danvers, MA, USA) is an aortic transvalvular microaxial pump designed to unload the left ventricle and to ensure a systemic flow in severe left ventricular dysfunction. Surgical implantation using femoral or right subclavian approach may be difficult in certain circumstances, such as encountered in peripheral vascular disease, patients with small vessels or during substantial use of vasoactive drugs responsible for vasospasm. We propose a simple and effective technique for implantation of the Impella 5.0 LVAD by means of a mini-sternotomy in patients with postinfarction refractory cardiogenic shock.

Target-controlled dosing of remifentanil during cardiac surgery reduces postoperative hyperalgesia.

OBJECTIVE: One of the strategies to attenuate opioid-induced hyperalgesia (OIH) may be to decrease intraoperative doses of opioids by using target-controlled infusion (TCI). DESIGN: Double-blind and randomized study. SETTING: A single university hospital. PARTICIPANTS: Forty American Society of Anesthesiologists II to III patients scheduled for elective cardiac surgery. INTERVENTIONS: patients were randomized to 1 of the 2 groups: 1 group received an infusion of intraoperative remifentanil using TCI (target: 7 ng/mL), and the 2nd one was given an intraoperative continuous infusion (CI) (0.3 µg/kg/min). The anesthestic protocol and postoperative pain management were the same in both groups. The extent of mechanical dynamic hyperalgesia on the middle line perpendicular to the wound was considered the primary endpoint. The secondary endpoints were other results of dynamic and punctuate hyperalgesia until postoperative day 7, visual analog scale (VAS) and verbal rating scale (VRS) scores, and total morphine consumption until postoperative day 2. MEASUREMENTS AND MAIN RESULTS: Morphometric and demographic characteristics and duration of surgery were comparable in both groups. Intraoperative remifentanil consumption was greater in CI than in TCI group (5,329 [1,833] v 3,662 [1,160] µg, p = 0.003). During the first 44 hours, there were no differences in morphine consumption, VAS, and VRS. The extent of hyperalgesia was significantly lower on postoperative days 1, 2, and 4 in the TCI group than in the CI group on the 3 evaluated lines (p < 0.05). Punctuate hyperalgesia evaluating 3 different points was lower in the TCI than in the CI group from postoperative day 1 until postoperative day 7 (p < 0.05). CONCLUSIONS: The intraoperative decrease of opioid consumption when comparing the CI versus TCI mode of administration of remifentanil led to less OIH after cardiac surgery.

Beating-heart coronary artery bypass surgery with the help of mini extracorporeal circulation for very high-risk patients.

BACKGROUND: Left ventricle dysfunction and co-morbidities are responsible for a large number of complications after coronary artery bypass graft (CABG) surgery. The best strategy for these patients, including the use or not and type of extracorporeal circulation (ECC), the use of minimized ECC (MECC), or conventional ECC (CECC), remains unclear. The aim of the present study was to investigate the potential effect of on-pump beating-heart (OPBH) surgery with the help of MECC for CABG in patients with a high-risk EuroSCORE and to compare this strategy to three other different procedures, including OPCAB and MECC or CECC with cardiac arrest. METHODS: Patients were included if their EuroSCORE was strictly >" xbd="1427" xhg="1404" ybd="1477" yhg="1440"/>9. Four groups were retrospectively compared: an OPCAB, an OPBH, a MECC and a CECC group under cardiac arrest. RESULTS: 214 patients, mean age 74.26 ± 8.5 years, 68.7% male, were operated. Mean EuroSCORE was 12.1 ± 2.9, left ventricular (LV) function 37.4 ± 12.3%, recent myocardial infarction (MI) 49.5%, renal failure 48.1%, chronic obstructive pulmonary disease (COPD) 42.2%, and peripheral vascular disease (PVD) 55.6%. Mean number of grafts per patient was 2.4 ± 0.7. Our study showed that it was possible, in very high-risk patients, to carry out revascularisation with OPBH similar to that using MECC or CECC under cardiac arrest (p=NS). This technique reduces troponin release (3.23 vs 6.56, p<0.01), postoperative myocardial complications (2% vs 8%, p<0.01), cardiotonic drug prescription (15.7% vs 31.3%, p<0.01), ventilation time (4.57H vs 6.48H, p<0.01) and length of stay (LOS) in ICU (2.16 vs 2.53, p=0.02). CONCLUSION: The OPBH method seems to be safe, secure and effective in this population of very high-risk patients, reducing early complications and multi-organ failure. OPBH surgery, combining MECC without aortic cross-clamping, makes it possible to perform complete revascularization and is an interesting alternative for CABG in high-risk patients.

Adjustment and characterization of an original model of chronic ischemic heart failure in pig.

We present and characterize an original experimental model to create a chronic ischemic heart failure in pig. Two ameroid constrictors were placed around the LAD and the circumflex artery. Two months after surgery, pigs presented a poor LV function associated with a severe mitral valve insufficiency. Echocardiography analysis showed substantial anomalies in radial and circumferential deformations, both on the anterior and lateral surface of the heart. These anomalies in function were coupled with anomalies of perfusion observed in echocardiography after injection of contrast medium. No demonstration of myocardial infarction was observed with histological analysis. Our findings suggest that we were able to create and to stabilize a chronic ischemic heart failure model in the pig. This model represents a useful tool for the development of new medical or surgical treatment in this field.

Echocardiographic analysis with a two-dimensional strain of chronic myocardial ischemia induced with ameroid constrictor in the pig.

Despite much progress in the medical management of myocardial ischemia, several problems remain and experimental models help to improve our understanding of the pathophysiology involved in this domain. The ameroid constrictor model is the most widely used to create ischemia but evaluation of patent ischemia is still under debate. In the present study, we describe the potential of a two-dimensional (2D) strain for experimentally evaluating myocardial ischemia in the pig. An ameroid constrictor was placed around the circumflex artery in 30 pigs. Angiography showed 90% stenosis at one and two months. Left ventricular function was moderately altered and associated with mitral valve insufficiency in 30% of cases. Longitudinal and circumference strains were dramatically modified in the ischemic inferior-lateral zone compared to the healthy anterior zone (P<0.01) at one and two months. We correlated these results to myocardial ischemia by using contrast echocardiography, which showed a significant reduction in myocardial perfusion in the ischemic zone compared to the uninjured area, and by using histological analysis. We showed that evaluation of the 2D strain could be an interesting approach for assessing myocardial ischemia after ameroid constrictor implantation. The 2D strain represents a useful tool for the evaluation of experimental models of myocardial ischemia.

Evaluation of continuous veno-venous hemofiltration for the treatment of cardiogenic shock in conjunction with acute renal failure after cardiac surgery.

BACKGROUND: Cardiogenic dysfunction with acute renal failure (ARF) and diuretic drug resistance increases mortality after cardiac surgery with cardiopulmonary bypass (CPB) in adults. Until few years ago, intermittent renal replacement therapy (IRRT) was the only therapeutical strategy proposed to such patients. Few data are available in the literature regarding the use of continuous veno-venous haemofiltration (CVVH) in this clinical context. The aim of our observational study was to evaluate the impact of CVVH strategy on ARF in conjunction with cardiogenic shock after cardiac surgery and on its well-known associated poor outcome. METHODS: During the period 2005-2006, we prospectively collected data from our database as we controlled the renal replacement therapy using CVVH (n=73). We also retrospectively collected data from our computerised database on patients who were treated with IRRT (n=68, period 2002-2003). Among CVVH-treated patients, a multivariate analysis of the data aimed to identify risk factors associated with 30-day mortality. RESULTS: In patients who presented with ARF in conjunction with cardiogenic shock after cardiac surgery, 30-day mortality rate was 59% for the IRRT group and 42% for the CVVH group. Within the CVVH group, the logistic regression and multivariate analyses reported that some variables were associated with higher mortality risk: a score F concerning the urinary output criteria of the RIFLE (risk, injury, failure, loss, end-stage kidney disease) classification (for scores R or I: odds ratio (OR): 0.01, 95% confidence interval (95% CI): 0.02-0.59; p=0.01), plasma bilirubin (OR: 1.44, 95% CI: 1.12-1.84; p=0.04), total CVVH duration <50h over 72 h (>50h; OR: 0.009, 95% CI: 0.04-0.93; p=0.01), the need of catecholamine support (OR: 12.88, 95% CI: 1.95-84.96; p=0.01), tachycardia in the intensive care unit (ICU; OR: 1.64, 95% CI: 1.02-2.65; p=0.04), surgery duration (<300 min; OR: 0.11, 95% CI: 0.02-0.71; p=0.02) and combined cardiac surgery (OR: 7.00, 95% CI: 1.29-37.88; p=0.02). CONCLUSION: In patients with ARF in conjunction with cardiogenic shock after cardiac surgery, renal replacement therapeutic strategy based on long-lasting CVVH could improve patients' outcome. The identification of risk factors associated with a poor outcome would help to better manage such patients in the ICU. Low total duration of CVVH within the first 72 h was one criteria related to poor outcome. This suggests that CVVH must be initiated as soon as possible when ARF with diuretic resistance occurs in patients after cardiac surgery and continued as long as possible for the first 3 days.

Prospective randomized study of early pulmonary evaluation of patients scheduled for aortic valve surgery performed by ministernotomy or total median sternotomy.

OBJECTIVE: The purpose of this study was to compare the respiratory function of patients operated either with a ministernotomy or with a conventional sternotomy for an aortic valve replacement. DESIGN: A prospective randomized study. SETTING: A single-institution university hospital. PARTICIPANTS: Seventy-eight patients scheduled for aortic valve replacement. INTERVENTIONS: Patients were assigned to have minimal sternotomy access (ministernotomy) or conventional median total sternotomy. Pulmonary function was measured using a mobile respiratory spirometric device preoperatively and after 1 (POD1), 2 (POD2), and 7 days (POD7) postoperatively. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in any respiratory parameter measured between the 2 groups of patients. Almost all respiratory volumes decreased significantly with the same intensity in the 2 groups on POD1 (p <0.05), by about 50% from baseline. Only functional residual capacity was unchanged from baseline in the postoperative period, except for a small but significant reduction of this parameter to 60.3% +/- 27.4% in the standard sternotomy group on POD1 and 60.9% +/- 27.1% and 58.8% +/- 30.4%, respectively, in the ministernotomy and the standard group at POD7. The only significant difference concerned the intraoperative blood loss measured at 450 +/- 280 mL and 720 +/- 450 mL, respectively, in the ministernotomy and the standard group (p < 0.05), but this was not significantly associated with a reduction of total blood use. CONCLUSION: This study failed to show any improvement of respiratory function by a smaller chest incision. However, it showed a significant reduction in intraoperative bleeding but without a reduction in transfusion. Further investigations are required to assess whether this procedure could improve the outcome of cardiac surgery patients with a greater predicted risk score or pulmonary diseases.

Off-pump coronary artery bypass surgery in very high-risk patients: adjustment and preliminary results.

Left ventricle dysfunction and comorbidities are responsible for a large number of complications after CABG. OPCAB could be an interesting alternative for very high-risk patients. Patients were included if EuroSCORE >9, or with at least two of the following criteria, severe LV dysfunction, recent myocardial infarction (MI), terminal renal failure, lung dysfunction, PVD, BMI>30. Patients were operated using the Octopus (Medtronic) system. One hundred and twenty patients, mean age 68+/-10 years, 72% male, were operated. Mean EuroSCORE was 10.2+/-5.3, LV function 36.79+/-11.3%, recent MI 57%, renal failure 52%, COPD 44%, PVD 52%, obesity 34%. Mean graft per patient was 2.1+/-0.8. Three patients underwent secondary PTCA treatment for incomplete revascularization. Combined surgery was required for 20%. Early mortality was 3%. Intensive care unit stay was 2.7 days. Early complications were: low output syndrome 3%, MI 0.8%, stroke 0.8%, kidney support 7%. Graft patency was systematically analyzed with MCTA or angiocardiography. OPCAB strategy seems to be safe and secure in this population of very high-risk patients reducing multi-organ failure. However, long-term results are needed to confirm this strategy.

Validation of a continuous, arterial pressure-based cardiac output measurement: a multicenter, prospective clinical trial.

INTRODUCTION: The present study compared measurements of cardiac output by an arterial pressure-based cardiac output (APCO) analysis method with measurement by intermittent thermodilution cardiac output (ICO) via pulmonary artery catheter in a clinical setting. METHODS: The multicenter, prospective clinical investigation enrolled patients with a clinical indication for cardiac output monitoring requiring pulmonary artery and radial artery catheters at two hospitals in the United States, one hospital in France, and one hospital in Belgium. In 84 patients (69 surgical patients), the cardiac output was measured by analysis of the arterial pulse using APCO and was measured via pulmonary artery catheter by ICO; to establish a reference comparison, the cardiac output was measured by continuous cardiac output (CCO). Data were collected continuously by the APCO and CCO technologies, and at least every 4 hours by ICO. No clinical interventions were made as part of the study. RESULTS: For APCO compared with ICO, the bias was 0.20 l/min, the precision was +/- 1.28 l/min, and the limits of agreement were -2.36 l/m to 2.75 l/m. For CCO compared with ICO, the bias was 0.66 l/min, the precision was +/- 1.05 l/min, and the limits of agreement were -1.43 l/m to 2.76 l/m. The ability of APCO and CCO to assess changes in cardiac output was compared with that of ICO. In 96% of comparisons, APCO tracked the change in cardiac output in the same direction as ICO. The magnitude of change was comparable 59% of the time. For CCO, 95% of comparisons were in the same direction, with 58% of those changes being of similar magnitude. CONCLUSION: In critically ill patients in the intensive care unit, continuous measurement of cardiac output using either APCO or CCO is comparable with ICO. Further study in more homogeneous populations may refine specific situations where APCO reliability is strongest.

Dextran sulfate included in factor Xa assay reagent overestimates heparin activity in patients after heparin reversal by protamine.

A lack of correlation between activated partial thromboplastin time (aPTT), thrombin time (TT) and anti-factor Xa (AXa) activity was observed in patients after cardiac surgery with cardiopulmonary bypass (CBP). Indeed, AXa activity measured by the chromogenic assay, Coamatic Heparin, was higher than expected with regard to results obtained in coagulation assays. To account for this discrepancy, another AXa chromogenic assay was tested. First, AXa activity was measured with two chromogenic assays (Coamatic Heparin and Rotachrom Heparin) in plasma samples of 25 patients undergoing cardiac surgery at two time points after heparin reversal by protamine. AXa activity was significantly higher when measured with Coamatic Heparin than with Rotachrom Heparin in samples collected just after protamine infusion (p<0.01). Next, since Coamatic( Heparin contains dextran sulfate (DXS) to reduce the influence of heparin antagonists such as platelet factor 4 (PF4), whereas Rotachrom Heparin does not, we hypothesized that the dextran sulfate contained in the reagent might explain this discrepancy. We therefore performed in vitro studies consisting in neutralizing unfractionated heparin (UFH) with protamine and measuring AXa activity with the two chromogenic assays. An AXa activity was still measurable with Coamatic Heparin after neutralization, thus strongly suggesting that dextran sulfate dissociates protamine/heparin complexes. We conclude that Coamatic Heparin assays should be avoided when measuring AXa activity in plasma samples immediately after protamine infusion, as inaccurate results may lead to inadequate management of heparin reversal.