Martin Dworschak

Platelet Dysfunction in Outpatients With Left Ventricular Assist Devices

BACKGROUND Thromboembolic and bleeding complications in outpatients with a left ventricular assist device are common and can be detrimental. A meticulous balance between anticoagulant and procoagulant factors is therefore crucial. However, in contrast to routinely performed plasmatic coagulation tests, platelet function is hardly ever monitored although recent reports indicated platelet dysfunction. We therefore differentially evaluated platelet function with four commonly used point-of-care devices. METHODS In a cross-sectional design platelet function was assessed in 12 outpatients and 12 healthy matched volunteers using thrombelastography platelet mapping, thromboelastometry, platelet function analyzer, and a new whole blood aggregometer (Multiplate). RESULTS Phenprocoumon produced an international normalized ratio of 3.5. It was associated with a twofold prolongation in the thromboelastometry clotting time (p < 0.001). Platelet function under high shear was severely compromised: collagen adenosine diphosphate closure times were 2.5-fold longer in patients than in volunteers (p < 0.001), and 50% of patients had maximal collagen adenosine diphosphate closure time values. Although antigen levels of von Willebrand factor were 80% higher in patients (p < 0.001), von Willebrand factor-ristocetin was subnormal in 5 of 12 patients. Ristocetin-induced aggregation was also threefold higher in volunteers (p < 0.001), indicating an additional functional defect of platelets affecting the glycoprotein Ib-von Willebrand factor axis. The von Willebrand factor multimer pattern in patients also appeared abnormal. CONCLUSIONS Multimodal antiplatelet monitoring showed markedly impaired platelet function in patients with a left ventricular assist device. Platelet dysfunction under high shear rates and abnormal ristocetin-induced aggregation is only partly attributable to low von Willebrand factor activity. These findings resemble the acquired von Willebrand syndrome that is associated with microaggregate formation and enhanced bleeding.

Risk factors of mortality and permanent neurologic injury in patients undergoing ascending aortic and arch repair

OBJECTIVES To analyze outcome in elderly patients after surgical repair of the ascending aorta and the aortic arch as compared with their younger counterparts and to determine risk factors of mortality and permanent neurologic injury. Patients and methods Between January 1995 and February 2003, a total of 369 patients underwent ascending aortic and arch repair. Indications for surgical intervention were acute type A dissections in 174 (47%) patients (<75 years, n = 147; > or =75 years, n = 27) and chronic atherosclerotic aneurysms in 195 (53%) patients (<75 years, n = 168; > or =75 years, n = 27). Emergency surgery was performed in 167 (45%) patients; 202 patients (54.7%) underwent surgery requiring deep hypothermic circulatory arrest. Pre- and intraoperative factors were evaluated by means of stepwise logistic regression analysis to determine risk factors of mortality and permanent neurologic injury. RESULTS Overall in-hospital mortality was 11.6%. In-hospital mortality with regard to indication for surgical intervention was comparable in both age groups (type A dissection: <75 years, 15.6%; > or =75 years, 18.5%; P =.731; chronic atherosclerotic aneurysm: <75 years, 7.7%; > or =75 years, 7.4%; P =.933). Permanent neurologic injury was observed in 5.0%. Permanent neurologic injury with regard to surgical intervention was comparable in both age groups (type A dissection: <75 years, 8.8%; > or =75 years, 3.7%; P =.359; chronic atherosclerotic aneurysm: <75 years, 3.0%; > or =75 years, 3.7%; P =.843). Stepwise logistic regression analysis revealed preoperative hemodynamic instability (odds ratio 4.3; P =.000), duration of cardiopulmonary bypass (odds ratio 2.1; P =.001), and permanent neurologic injury (odds ratio 1.7; P =.033) but not age as independent predictors affecting mortality. Utilization of but not duration of deep hypothermic circulatory arrest was the only independent predictor of permanent neurologic injury (odds ratio 2.8; P =.019). CONCLUSIONS Age shows a trend toward a higher risk of mortality but does not predict a higher incidence of permanent neurologic injury after ascending aortic and arch repair. As utilization of deep hypothermic circulatory arrest remains the only independent predictor of permanent neurologic injury, alternative approaches to maintain cerebral perfusion during ascending aortic and arch repair are warranted.

Comparison of the effects of albumin 5%, hydroxyethyl starch 130/0.4 6%, and Ringer's lactate on blood loss and coagulation after cardiac surgery

BACKGROUND Infusion of 5% human albumin (HA) and 6% hydroxyethyl starch 130/0.4 (HES) during cardiac surgery expand circulating volume to a greater extent than crystalloids and would be suitable for a restrictive fluid therapy regimen. However, HA and HES may affect blood coagulation and could contribute to increased transfusion requirements. METHODS We randomly assigned 240 patients undergoing elective cardiac surgery to receive up to 50 ml kg(-1) day(-1) of either HA, HES, or Ringers lactate (RL) as the main infusion fluid perioperatively. Study solutions were supplied in identical bottles dressed in opaque covers. The primary outcome was chest tube drainage over 24 h. Blood transfusions, thromboelastometry variables, perioperative fluid balance, renal function, mortality, intensive care unit, and hospital stay were also assessed. RESULTS The median cumulative blood loss was not different between the groups (HA: 835, HES: 700, and RL: 670 ml). However, 35% of RL patients required blood products, compared with 62% (HA) and 64% (HES group; P=0.0003). Significantly, more study solution had to be administered in the RL group compared with the colloid groups. Total perioperative fluid balance was least positive in the HA group [6.2 (2.5) litre] compared with the HES [7.4 (3.0) litre] and RL [8.3 (2.8) litre] groups (P<0.0001). Both colloids affected clot formation and clot strength and caused slight increases in serum creatinine. CONCLUSIONS Despite equal blood loss from chest drains, both colloids interfered with blood coagulation and produced greater haemodilution, which was associated with more transfusion of blood products compared with crystalloid use only.

Lessons learned from the first clinical implants of the DeBakey ventricular assist device axial pump: a single center report

BACKGROUND The bridge to transplantation with pulsatile mechanical assist devices became a standard procedure for patients deteriorating on the waiting list. Recently, continuous flow axial impeller pumps were introduced to clinical application offering new advantages. METHODS From November 1998 till September 2000, 6 male patients (mean age 53 plus or minus 11 years) with end-stage left heart failure were implanted with a DeBakey ventricular assist device (VAD) axial-flow pump for bridge to transplantation. RESULTS Three patients were successfully transplanted after 74, 115, and 117 days, respectively. Two other patients died after 25 and 133 days. One patient is still on the device after 108 days. Because of modification of the implantation technique after the first 2 patients, mean pump-flow within the first 3 weeks was increased from 4.3 +/- 0.6 L/min to 6.7 +/- 0.3 L/min. Patients were put on regular bicycle-ergometer training and improved their exercise capacities up to a mean maximum oxygen consumption of 20.2 mL/kg/min. CONCLUSIONS Initial implants of the DeBakey VAD demonstrated support properties comparable to pulsatile pumps but without significant restrictions for extended use.

Release of neuron-specific enolase and S100 after implantation of cardioverters/defibrillators.

ObjectiveRepeated induction of ventricular fibrillation with ensuing alterations in electroencephalogram and jugular venous oxygen saturation is common practice during insertion of transvenous implantable cardioverters/defibrillators. We investigated whether these functional changes are also associated with cerebral injury. DesignProspective study. SettingUniversity hospital. PatientsWe studied 45 patients undergoing implantable cardioverter/defibrillator insertion. Eleven patients with cardiac pacemaker implantation, which was performed in the same manner yet without the necessity to induce ventricular fibrillation, served as controls. Measurements and Main ResultsSerum neuron-specific enolase and S100 were determined before, immediately postoperatively, and 2 hrs postoperatively. In a randomly composed subgroup, neuron-specific enolase was also determined 6 and 24 hrs after surgery. Implantable cardioverter/defibrillator patients only showed an increase of both markers postoperatively. Median neuron-specific enolase values climbed from a preoperative 9.9 to 12.3 and 14.4 &mgr;g/L at 2 and 24 hrs after surgery, respectively. This increase was associated with the number of shocks and the cumulative time in circulatory arrest. The highest median S100 level (0.075 &mgr;g/L) was reached 2 hrs after the procedure. Neuron-specific enolase and S100 were extremely elevated (13.7 and 0.970 &mgr;g/L, respectively) in one patient after an extended episode of ventricular fibrillation. Plasma hemoglobin levels were in the normal range in implantable cardioverter/defibrillator patients throughout the observation period. ConclusionsApparently, even brief successive periods of global cerebral ischemia cause neuronal damage without obvious severe neurologic deficits. However, they may be related to subtle postoperative neurologic or cognitive dysfunctions that a number of implantable cardioverter/defibrillator patients exhibit after implantation.

Alpha-Gal specific IgG immune response after implantation of bioprostheses.

BACKGROUND We have previously shown that the alpha-Gal (Galalpha1.3-Galbeta1-4GlcNAc-R) epitope is a relevant xenoantigen present on bioprostheses utilized in cardiac surgery and elicits an alpha-Gal specific IgM immune response. We sought to investigate whether that immune response continues after valve implantation. MATERIALS AND METHODS We collected plasma samples from patients who underwent bioprosthesis implantation (n = 19) or mechanical valve replacement (n = 8), respectively, prior to, at 10 days and at 3 months after cardiac surgery. ELISA was utilized to quantify alpha-Gal specific IgG and IgG subclasses. 3 bioprosthetic tissue samples were obtained from patients who had to undergo re-operation within 1 week (n = 1) or at 12-15 months (n = 2) after the initial operation. We utilized confocal laser scanning microscopy (CLSM) to detect the presence of alpha-Gal epitopes (IB4) and cell nuclei (DAPI). RESULTS alpha-Gal specific IgG was significantly increased 3 months after implantation of bioprostheses compared to preoperative values (p < 0.001) and was significantly higher than alpha-Gal specific IgG levels of the control group (p < 0.05). IgG3 was the major subclass directed against alpha-Gal (p < 0.05, pre- vs. postoperative values). In CLSM analysis we demonstrated that bioprostheses explanted 1 week after implantation contained IB4/DAPI positive cells within the collagen matrix. In contrast, in patients who underwent reoperation after 12 months, porcine tissue showed a complete lack of IB4/DAPI. CONCLUSION Our results indicate that the implantation of bioprostheses elicits a specific humoral immune response against alpha-Gal bearing cells compared to controls within 3 months after cardiac surgery. The complete absence of IB4/DAPI positive structures 12 months after implantation indicates a specific degradation of alpha-Gal bearing cells through previous exposure to the human blood circuit.

Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD.

Introduction: Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major cause of death. The disease is accompanied by chronic inflammation and increased cellular turnover that is partly due to an overwhelming induction of apoptosis. In this study, we hypothesized that systemic markers of apoptosis are altered in patients with mild‐to‐severe COPD.

Cerebral desaturation during cardiac arrest: its relation to arrest duration and left ventricular pump function.

Objective:To determine the impact of brief periods of cardiac arrest (CA) on regional cerebral oxygen saturation (rSo2) in patients with low left ventricular ejection fraction (LVEF <30%). Design:Prospective observational study. Setting:Cardiac surgery room at a university hospital. Patients:Seventy-seven consecutive patients undergoing elective implantation of a cardioverter/defibrillator in monitored anesthesia care. According to preoperative assessments, left ventricular function was classified as normal (LVEF >50%), moderately impaired (LVEF 30%–50%), or severely reduced (LVEF <30%). Interventions:None. Measurements and Main Results:rSo2 was determined during threshold testing with concomitant induction of CA. In patients with LVEF <30%, mean baseline rSo2 (59%) was already below the lower range of normal despite normal arterial blood pressure, heart rate, and arterial oxygen saturation. rSo2 increased by 6% after 6 L/min oxygen insufflation (p < 0.05) and dropped again in each group after CA, reaching a nadir after successful defibrillation. Patients with LVEF <30% and baseline rSo2 ≤63% exhibited the lowest values. They also showed the highest incidence (11%) of critical cerebral desaturations (i.e., >20% drop from baseline or rSo2 value <50%). rSo2 in patients with LVEF <30% was always below that determined in patients with LVEF >30% (p < 0.05). There was a strong correlation between rSo2 values before CA and rSo2 nadir (p < 0.05). The drop in rSo2 was only moderately related to the brief CAs (p < 0.05). Conclusion:These findings demonstrate that severely compromised left ventricular pump function is associated with diminished rSo2. As these patients seem to be more susceptible to critical desaturations, they may be prone to severe tissue hypoxemia unless adequate oxygen delivery is reestablished rapidly. This may contribute to the poor neurologic outcome after successful resuscitation in patients with LVEF <30%.

Secretion of soluble ST2 - possible explanation for systemic immunosuppression after heart surgery.

BACKGROUND Cardiopulmonary bypass is known to affect cytokine release leading to a generalized endogenous immune reaction similar to that described in sepsis, without having been explored in great detail. Therefore we evaluated the anti- and pro-inflammatory cytokine responses after heart surgery. METHODS 16 patients who underwent coronary artery bypass graft (CABG) surgery with extracorporeal circulation were included. ST2, IL-4 and IL-10 served as markers for TH2 cytokine response; IL-6, IL-8 and IFN-gamma as TH1 markers. Furthermore, total immunoglobulin subtype analysis (IgM, IgG, IgE) was performed. RESULTS Serum levels of soluble ST2 started to climb at 60 minutes (from 38 +/- 14 preoperatively to 1 480 +/- 890 pg/ml) and peaked 24 hours after surgery (13 360 +/- 2 840 pg/ml, P < 0.001). IL-10 reached a maximum at 60 minutes and returned to baseline levels 24 hours later. IL-6 and IL-8 levels peaked 60 minutes after surgery. IL-4 and IFN-gamma did not change. Only IgM showed a significant peak on day eight ( P < 0.001). CONCLUSION Our results demonstrate that CABG surgery induces a massive long-lasting secretion of ST2, a protein related to immune suppression.

Neuronal injury after repeated brief cardiac arrests during internal cardioverter defibrillator implantation is associated with deterioration of cognitive function.

To determine the degree of neurocognitive dysfunction after placement of internal cardioverter defibrillators (ICD) and its relationship to the extent of neuronal injury, we studied 42 patients undergoing ICD (n = 21) or pacemaker (PM) insertion (control patients, n = 21). The Mini Mental State Examination, the Trailmaking A test and the forward and backward Digit Span tests were used and P300 latencies were determined preoperatively and postoperatively. Serum neuron-specific enolase (NSE) was determined before and at the end of, as well as 2, 6, and 24 h after surgery. Preoperatively, PM patients scored worse in the Digit Span backward and the Trailmaking tests and showed prolonged P300 latencies. Postoperatively, the Digit Span backward scores declined and NSE levels increased only in the ICD group (P ≤ 0.05). The difference between preoperative and postoperative Digit Span backward scores correlated with the increase in serum NSE levels (r2 = 0.3, P ≤ 0.05). Moreover, P300 latencies increased in 13 of 17 ICD patients, but decreased in 7 of 10 PM patients (P ≤ 0.05). PM patients even improved in the Trailmaking test (P ≤ 0.05). Neuronal injury from even brief periods of global brain ischemia seems to be associated with deteriorating neurocognitive function.