Thromboembolic complications during weaning from right ventricular assist device support.

We report on two patients who experienced life-threatening thromboembolic complications during prolonged weaning from Levitronix CentriMag right ventricular assist device support. Right ventricular assist device flow in both patients was reduced below 2 L/min for a period of 72 or 36 h to closely monitor patients' hemodynamics and echocardiography because the extent of right ventricular recovery was difficult to assess. Thrombus formation occurred despite adjusting the heparin dosage to achieve partial prothrombin time values between 60 and 70 s. Periods of reduced flow during Levitronix CentriMag support must be kept short, and an additional bolus dose of heparin should be considered.

Detection of protamine and heparin after termination of cardiopulmonary bypass by thrombelastometry (ROTEM): results of a pilot study.

BACKGROUND: Our goal of this study was to determine whether protamine's effects on coagulation can be detected and differentiated from those of heparin when using thrombelastometry (ROTEM). METHODS: To reverse the effects of heparin after cardiopulmonary bypass (CPB), 22 consecutive patients undergoing aortocoronary bypass graft surgery were included. According to clinical routine, all patients received a first dose of protamine calculated from the total amount of heparin given; additional protamine (70 U/kg) was administered to patients with activated clotting time (ACT) above baseline and clinical signs of diffuse bleeding. Simultaneously, routine ACT measurements, ROTEM assays (heparin-sensitive INTEM, and heparinase-containing HEPTEM test) and standard coagulation tests were performed, and the activity of coagulation factors as well as antifactor Xa activity measured. RESULTS: Administration of additional protamine (n = 16) resulted in a statistically significant increase in coagulation times on the intrinsically activated test (INTEM-CT), namely from (mean [+/-SD]) 219.8 (+/-19.1) s to 241.1 (+/-21.7) s (P < 0.001), and on the heparinase-containing test (HEPTEM-CT), namely from 210.2 (+/-19.9) s to 226.8 (+/-21.8) s (P < 0.001). These changes were not observed in patients receiving a single protamine dose (n = 6). The INTEM-CT:HEPTEM-CT ratio correctly identified 56 of the 58 samples as not containing residual heparin and correctly detected residual heparin in 3 of the only 6 samples showing elevated antifactor Xa values after CPB. CONCLUSION: Our preliminary data show that at termination of CPB administration of additional protamine results in a brief prolongation of coagulation times on the INTEM and HEPTEM test and that ROTEM might be useful in excluding residual heparin in cases showing prolonged ACT.

Mechanism of neopterin-induced myocardial dysfunction in the isolated perfused rat heart.

Neopterin is a sensitive marker for diseases involving increased activity of the cellular immune system in humans. Many studies, however, provide evidence for neopterin not only as a marker, but also for its characteristic effects. Recently, we were able to demonstrate a considerable influence of exogenous neopterin at a concentration of 100 mumol/l on cardiac performance in the Langendorff model of isolated perfused rat hearts. The present study was designed to investigate its possible mechanism. During co-infusion of neopterin at a concentration of 100 mumol/l with the unspecific nitric oxide synthase inhibitor N(G)-monomethyl-l-arginine monoacetate, the nitric oxide donor PAPA NONOate, the free radical scavenger N-acetylcysteine, or the pro-inflammatory cytokine tumor necrosis factor-alpha the effects on cardiac contractility parameters and coronary vascular resistance were studied in 67 male Sprague-Dawley rats. The temperature-controlled and pressure-constant Langendorff apparatus was used with retrograde perfusion of the aorta and a Krebs-Henseleit buffer. Neither the unspecific nitric oxide synthase inhibitor nor the nitric oxide donor excludes nitric oxide from playing a mechanistic role in our perfusion studies. Tumor necrosis factor-alpha was without any synergistic or antagonistic effects when co-treated with neopterin. N-acetylcysteine was most effective in abolishing neopterin-dependent effects on cardiac function. The negative effects of neopterin on cardiac performance might be due to an enhancement of oxidative stress by neopterin that can be attenuated by the antioxidant N-acetylcysteine. Neopterin has to be considered a pathogenic factor in the development of cardiac dysfunction in chronic disease states with high neopterin levels secondary to activation of the immune system.

Slightly elevated serum creatinine predicts renal failure requiring hemofiltration after cardiac surgery.

BACKGROUND: Acute renal failure (ARF) after cardiac surgery is a serious adverse event that is associated with high perioperative mortality and prolonged hospitalization. The aim of our study was to evaluate pre- and intraoperative risk factors for the development of ARF requiring hemofiltration after cardiac surgery. METHODS: From February 2002 through February 2003, 913 patients underwent cardiac surgery at our institution. Seventy-three patients developed ARF (8.1%), 16 patients were excluded from the study because of chronic end-stage renal insufficiency. Patient characteristics and operative variables were analyzed. A multivariate logistic regression analysis was performed to determine risk factors for ARF. RESULTS: Patients who developed ARF were older (P < .001; odds ratio [OR], 1.084; 95% confidence interval [CI], 1.0371.133) than patients who did not develop ARF. Furthermore, cardiopulmonary bypass duration (P = .007; OR, 1.013; 95% CI, 1.004-1.032) and emergent surgery (P = .011; OR, 6.667; CI, 1.538-28.571) were predictive for development of ARF. The strongest predictor for ARF was a preoperative creatinine level >or=2 mg/dL (P < .001; OR, 97.519; 95% CI, 22.363425.252). Most interestingly, even moderately elevated preoperative creatinine levels (1.3-1.99 mg/dL) independently predict ARF after cardiac surgery (P = .001; OR, 3.838; 95% CI, 1.793-8.217). CONCLUSION: Our data indicate that emergent surgery as well as advanced age and long duration of cardiopulmonary bypass independently predict ARF after cardiac surgery. Most importantly, even slightly impaired preoperative creatinine levels predict the development of ARF requiring hemofiltration after cardiac surgery.

Successful transfer of a cardiac allograft from a heterotopic to an orthotopic position 16 years after transplantation.

The ever-increasing donor shortage sometimes demands unusual solutions. This article reports the first successful reuse of a heterotopically implanted heart, which was transferred to an orthotopic position 16 years after transplantation following definitive failure and removal of the native heart. The surgically demanding procedure succeeded without complications, and, 16 weeks later, the patient is classified as New York Heart Association I.

Coagulation monitoring and management of anticoagulation during cardiac assist device support.

BACKGROUND: The incidence of clinically significant thromboembolic events due to the use of cardiac assist device systems remains high. Despite the considerable advances in cardiac assist device technology, the monitoring and management of the hypercoagulable coagulation status, resulting from foreign surfaces of the assist device system, altered rheologic conditions, and blood stasis in the recipient heart remain a challenge. Moreover septic complications and insufficient anticoagulation are responsible for thromboembolic events. METHODS: In addition to standard coagulation analysis, functional coagulation tests were performed including the use of a thrombelastographic monitoring system (ROTEG) and a platelet function analyzer (PFA-100). RESULTS: Severe biventricular ischemic heart failure developed in a 58-year-old man with acute myocardial infarction and he needed a biventricular assist device for a bridge to cardiac transplantation. Although the patient received acenocoumarol (Sintrom; Novartis Pharma, Vienna, Austria) and acetylsalicylic acid (Aspisol; Bayer AG, Leverkusen, Germany) as usual, ROTEG and the PFA-100 detected hypercoagulability while routine coagulation screening tests showed hypocoagulability. Moreover thrombus formation surrounding the canula of the left ventricular assist device was detected. Antithrombotic therapy with clopidogrel (Plavix) was initiated. Coagulation was closely monitored with modified thrombelastography and the PFA-100 to achieve sufficient but not overwhelming anticoagulation therapy. Three months after biventricular assist device implantation the patient underwent successful transplantation with no major blood loss. CONCLUSIONS: Thrombelastography should be the standard form of monitoring in such patients to decrease the risk of thromboembolic events and prevent bleeding complications.

Influence of antithrombin on ischemia/reperfusion injury in the isolated blood-free perfused rat heart.

INTRODUCTION: Antithrombin (AT) is well known as an important inhibitor of the coagulation system. An interesting new hypothesis is that antithrombin exerts specific anti-inflammatory effects by stimulating the production of prostacyclin in endothelial cells. Recent studies report beneficial influence on ischemia/reperfusion injury in several organs. These effects are independent of the coagulation system. We investigated the influence of antithrombin on ischemia/reperfusion injury and prostacyclin release in the isolated rat heart. Since the perfusion of the hearts was without blood, the used model essentially describes effects of antithrombin on endothelial cells. MATERIAL AND METHODS: Experiments were performed using the temperature-controlled and pressure-constant Langendorff apparatus. The hearts of 32 male Sprague-Dawley rats were subjected to 20 min of global ischemia followed by 30 min of reperfusion. Antithrombin was administered in three different concentrations (1, 4 and 8 U/ml) 15 min prior to global ischemia. Cardiac contractility parameters and biochemical parameters were measured. RESULTS: Treatment with antithrombin did not increase the release of prostacyclin significantly after ischemia. Antithrombin at a concentration of 8 U/ml led to a significant increase in creatine kinase (CK; p<0.05) and troponin I (p<0.05), whereas measurements of lactate dehydrogenase (LDH) revealed no significant differences between treated and untreated hearts. CONCLUSION: Our study shows that antithrombin did not reduce ischemia/reperfusion injury in the isolated heart, and prostacyclin is not significantly released following antithrombin treatment. High concentrations of antithrombin, however, might have a negative influence on the reperfused heart. The underlying mechanism remains unclear.

The effects of perioperatively administered crystalloids and colloids on concentrations of molecular markers of activated coagulation and fibrinolysis.

To explore whether intravenous administration of routinely used crystalloid or colloid solutions differently affects the coagulation system, we investigated orthopaedic patients. Since crystalloid solutions might cause hypercoagulability, we here present our results on molecular markers of coagulation and fibrinolysis. Patients undergoing knee replacement surgery randomly received isovolemic amounts of lactated Ringer's solution, 6% hydroxyethyl starch 200/0.5 or 4% modified gelatine. Arterial blood samples for determination of specific molecular markers of activated coagulation (thrombin/antithrombin complex, D-dimer, prothrombin fragment F1 + 2), fibrinolysis (plasmin/alpha 2-antiplasmin complex, tissue plasminogen activator, plasminogen activator inhibitor-1), and concentrations of coagulation factor XIII were obtained at baseline, before tourniquet release, at the end of surgery and 2 h after operation. During the observation period, thrombin/antithrombin complex increased from 4.8 to 54.7 microg/l, D-dimer increased from 0.3 to 6.0 mg/ml, prothrombin fragment F1 + 2 increased from 1.7 to 5.9 nmol/l, tissue plasminogen activator decreased from 7.3 to 6.7 ng/ml, plasminogen activator inhibitor-1 increased from 68.4 to 71.0 ng/ml, plasmin/alpha 2-antiplasmin complex increased from 281.5 to 884 microg/l and factor XIII decreased from 89.0 to 58.5%. All parameters changed significantly but without any detectable difference in the response profile between the groups receiving different intravenous fluids. During knee replacement surgery a pronounced activation of the coagulation/fibrinolytic system was observed, regardless of whether patients received crystalloid or colloid fluids. Thus, these results cannot confirm the hypothesis that crystalloid fluids per se cause hypercoagulability in vivo.

[Is it possible to reduce CMV-infections after heart transplantation with a three-month antiviral prophylaxis? 7 years experience with ganciclovir]. / Können CMV-Infekte nach Herztransplantation durch dreimonatige antivirale Prophylaxe reduziert werden? 7 Jahre Erfahrung mit Ganciclovir.

BACKGROUND: In the early phase after heart transplantation (HTX) patients are at high risk for infection because of intensified immunosuppression. This retrospective study evaluates the efficacy of a three-month antiviral cytomegalovirus (CMV) prophylaxis. PATIENTS AND METHODS: 133 patients received a three-month combined intravenous and oral CMV prophylaxis with Ganciclovir (Cymevene after HTX between 1997 and April 2003 (group II). They were compared to a historical group consisting of 40 patients, who had undergone HTX between 1995 and 1996 (group I; CMV-prophylaxis: hyperimmune globuline (Cytotect) for the first post-operative month in combination with orally administered aciclovir (Zovirax) for 6 months). Demographic data of organ recipients and donors in both groups were comparable, except for underlying cardiac diseases (p = 0.016). All patients had identical postoperative immunosuppressive regimes. RESULTS: Group II had a significantly lower mortality rate (GI: 37.5%, GII: 9.8%; p < 0.001); one year survival (p = 0.001) and overall survival (p = 0.001) were significantly better than in group I. Patients of group II had fewer rejection episodes > or = grade II ISHLT requiring treatment (p < 0.001). Group II presented significantly fewer positive CMV blood samples (p = 0.005) and CMV infections (26% versus 47,5% in GI; p = 0.008), and a later onset of infections after HTX than group I (group I with a mean interval of 5.8 weeks after HTX, group II: 24.8 weeks after HTX; p < 0.001). CONCLUSION: Incidence of CMV infection was significantly lowered under ganciclovir prophylaxis, infections occurred at a later time point after HTX, when patients were immunologically more competent. The proportion of higher grade rejection episodes was markedly reduced and survival was improved.

Special problems of pacing in children.

The number of children suffering from congenital or acquired rhythm disorders, and therefore being pacemaker dependent, is very small. This is one of the reasons why a special hardware has never been developed for this cohort. Pacemaker implantation into children does not differ substantially from operations in adults. But there are several important points which have to be fulfilled in these small patients in order to guarantee a complication free function. As most of these children remain pacemaker dependent a lifetime, it is of tremendous importance to minimize all revisions regarding the implanted systems and to enable our small patients a high and therefore nearly normal quality of life. Pros and cons of different surgical approaches, implantation sites and the problem of growth after pacemaker implantation in children are considered.

The pediatric mechanical circulatory support program in Innsbruck, Austria, and the impact of such programs on lack of donor hearts in Europe.

Strategy and results of the Innsbruck Mechanical Circulatory Support Program are presented, and the impact of such programs on pediatric heart transplantation (HTX) in Europe is discussed. Venoarterial extracorporeal membrane oxygenation (vaECMO) and ventricular assist devices (VADs) were used in 21 pediatric patients (median age 3.3 years, 2 days to 17 years) for acute heart failure (AHF) following a bridge or bridge-to-bridge strategy. Twelve patients were treated with vaECMO: eight were weaned after 2-10 days, two died, and two were switched to a VAD. Of the last, one was weaned 47 days later and the other underwent HTX 168 days later. In nine patients, VAD was implanted without preceding vaECMO. One such patient died (cerebral hemorrhage) after 236 days; of the remaining eight patients three were weaned and five underwent HTX. Waiting time for HTX (high-urgency status) varied from 4 to 372 days. Fifteen patients were discharged (follow up: 2-74 months); 14 are doing very well (New York Heart Association (NYHA) Functional Classification Class I, neurologically normal), whereas one suffers from severe neurologic damage, presumably from resuscitation before vaECMO. Data from Eurotransplant on pediatric HTX in 2004, 2005, and 2006 (33, 49, and 34 transplanted hearts, respectively; recipients <16 years of age) are discussed. Mechanical circulatory support (MCS) substantially improves survival with AHF in pediatric patients. Medium-term support (up to 400 days in our patients) is possible and outcome of survivors is excellent. Wide spread use of MCS might slightly aggravate the lack of donor organs, which could result in longer support times.

Robotic totally endoscopic coronary artery bypass and catheter based coronary intervention in one operative session.

A 56-year-old male patient underwent robotically assisted totally endoscopic left internal mammary artery (LIMA) to left anterior descending artery (LAD) grafting. After protamine administration complete heart block developed in the patient. On intraoperative angiography the LIMA to LAD graft was perfectly patent but an acute occlusion of the right coronary artery (RCA) was noted. We performed an immediate on table percutaneous coronary angioplasty and stent placement to the RCA. The heart regained sinus rhythm and the wall motion abnormalities on the back wall of the heart resolved. No clinical symptoms indicating ongoing myocardial ischemia were noted postoperatively. This case demonstrates that a hybrid procedure of robotic totally endoscopic coronary artery bypass grafting and catheter based coronary intervention is feasible in one simultaneous session.

Systolic anterior motion of the mitral valve with left ventricular outflow tract obstruction: three cases of acute perioperative hypotension in noncardiac surgery.

In this report we describe three cases of severe perioperative hypotension in noncardiac surgery patients. As systolic anterior motion of the mitral valve in combination with subaortic left ventricular outflow tract obstruction is an unrecognized cause for hypotension in noncardiac surgery patients, delayed diagnosis can result in erroneous treatment regimen. The aim of the present report is to provide an informative and brief synopsis of the pathophysiological consequences and diagnostic/therapeutic strategies for the perioperative management of systolic anterior motion.

Life-threatening mediastinal hematoma caused by extravascular infusion through a triple-lumen central venous catheter.

We report a case of life-threatening mediastinal hematoma in a 6-mo-old girl during surgical correction of scaphocephaly. The hematoma was caused by extravascular infusion via the proximal lumen of a dislocated triple-lumen central venous catheter (CVC). Worsening symptoms of hypovolemia and ventilation problems prompted performance of transesophageal echocardiography, which reliably and quickly allowed us to exclude pericardial tamponade and detect a mediastinal hematoma. The anesthesiologist should be alert when a patient with a CVC develops acute cardiopulmonary or respiratory symptoms. Repeated aspirations of blood, especially after major positional changes and before giving large quantities of fluid or blood, should be performed to detect secondary malposition of the CVC.

Experience with percutaneous venoarterial cardiopulmonary bypass for emergency circulatory support.

OBJECTIVE: Mechanical circulatory support can maintain vital organ perfusion in patients with cardiac failure unresponsive to standard pharmacologic treatment. The purpose of the current study was to report complication and survival rates in patients supported with emergency percutaneous venoarterial cardiopulmonary bypass because of prolonged cardiogenic shock or cardiopulmonary arrest. DESIGN: Retrospective clinical study. SUBJECTS: A total of 46 patients supported with venoarterial cardiopulmonary bypass, 25 because of cardiogenic shock unresponsive to pharmacologic therapy and 21 because of cardiopulmonary arrest unresponsive to standard advanced cardiac life support. RESULTS: In 41 of the 46 patients (89%), stable extracorporeal circulation was established; in five patients (11%), femoral cannulation was accomplished only after a surgical cutdown. A total of 28 patients were weaned from cardiopulmonary bypass (19 of 25 patients with cardiogenic shock vs. 9 of 21 patients with cardiopulmonary arrest, p =.03), and 13 patients had long-term survival (10 of 25 patients with cardiogenic shock vs. 3 of 21 patients with cardiopulmonary arrest, p =.1). Complications directly related to the use of cardiopulmonary bypass were found in 18 patients (39%), major complications related to femoral cannulation being the most common single cause for bypass-associated morbidity (eight patients, 17%). CONCLUSIONS: Long-term survival rates after emergency percutaneous cardiopulmonary bypass are encouraging in patients with an underlying cardiocirculatory disease amenable to immediate corrective intervention (angioplasty, surgery, transplantation).

The effects of perioperatively administered colloids and crystalloids on primary platelet-mediated hemostasis and clot formation.

UNLABELLED: To explore whether routinely administered colloids and crystalloids influence the hemostatic system, we studied 60 patients undergoing knee replacement surgery during randomized intravascular fluid administration using 6% hydroxyethyl starch 200/0.5 (HES) or 4% modified gelatin (GEL) in addition to a basal infusion of lactated Ringer's solution (RL), or exclusively RL. In addition to routine coagulation tests, measurements of coagulation factors were performed. Also, functional measurements of the in vitro bleeding time by use of the platelet function analyzer (PFA-100 and ROTEG analysis (ROTEG(R); extrinsically and intrinsically [Ex; In] activated measurements of clotting time, CT [s]; clot formation time, CFT [s]; clot strength, A20 [mm]; fibrinogen component of the clot, FibA20 [mm]; and maximal clot elasticity) were used. Time dependency of variables was analyzed with a repeated-measures analysis of variance (all groups pooled); differences between groups were detected by comparing the calculated area under the curve (AUC(A-D)). For all variables, except ExCT, ExCFT, and InCFT, a significant time dependency was demonstrated, indicating that impaired platelet-mediated hemostasis and clot formation occurred with IV administration of fluids. Total clot strength, fibrinogen part, and clot elasticity decreased significantly more in the colloid groups than in the RL group (InA20: HES, -13.0 mm; GEL, -11.5 mm; RL, -1.3 mm; P = 0.042; FibA20: HES, -10.5 mm; GEL, -6.0 mm; RL, -1.3 mm: P < 0.0001; MCE: HES, -48; GEL, -35; RL, -15.8; P < 0.0001). The decrease in fibronectin concentrations was significantly smaller with GEL as compared with HES, whereas a weak trend toward a larger decrease in fibrinogen concentrations was observed with both colloids. Results show that colloid administration reduces final clot strength more than does RL alone, which also exhibited effects, albeit minor, on the coagulation system. The reduction in total clot strength was due to impaired fibrinogen polymerization, resulting in a decreased fibrinogen part of the clot and reduced clot elasticity. IMPLICATIONS: Our data suggest that during deliberate colloid administration, critically impaired fibrinogen polymerization and reduced fibrinogen concentrations might be reached earlier than expected. Therefore, maintaining fibrinogen concentrations seems essential when continuing blood loss is bridged by colloid infusion until transfusion triggers are reached, especially in patients already exhibiting borderline fibrinogen levels at baseline.