Ioanna Apostolidou

Alterations in temporal patterns of heart rate variability after coronary artery bypass graft surgery

Background:Preliminary studies have Indicated that autonomic nervous system dysfunction may be present in patients after cardiac surgery. The purpose of this study was to evaluate cardiac autonomic nervous system function, as assessed by analysis of heart rate variability (HRV), in adult patients undergoing uncomplicated coronary artery bypass graft surgery. Methods:Longitudinal changes in HRV were determined perioperatlvely by continuous electrocardiographs monitoring in 40 adult patients undergoing elective coronary artery bypass graft surgery and were compared with HRV in two groups of control subjects: 15 patients undergoing nonthoracic major vascular surgery and 19 healthy volunteers. Exclusion criteria were diabetes, renal failure, recent or perioperatlve myocardial infarction, or use of inotropic drugs. HRV data during electrocardiographically documented episodes of myocardial ischemia were omitted. Results:There were no differences in any measurement of preoperative HRV between groups during the day, but HRV was greater at night (12:00 AM to 5:00 AM) in volunteers than in patients in either surgical group. In the hour after induction of anesthesia (before cardiopulmonary bypass), the components of HRV were decreased compared with those in the preoperative daytime but were similar in the two surgical groups. After surgery, HRV in the group undergoing nonthoracic vascular surgery remained at about the same level as that observed after induction of anesthesia, whereas in the group undergoing coronary artery bypass graft surgery, HRV was further reduced and was approximately 40-50% less than that in the vascular surgery group (P < 0.05). in the coronary artery bypass group, the reduction in HRV compared with the preoperative daytime measurements persisted on postoperative day 5. Conclusions:HRV is reduced after uncomplicated coronary artery bypass graft surgery. Although we cannot exclude the effects of uncontrolled variables in this reduction of postoperative HRV, the observed changes in HRV did not appear to result from general anesthesia, perioperative stress responses, and other factors associated with the early postoperative period. These data are consistent with the supposition that cardiac autonomic nervous system function is impaired after cardiac surgery.

Genetic variants of surfactant proteins A, B, C, and D in bronchopulmonary dysplasia

BPD_28D (O2 dependency at 28 days of life) and BPD_36W (O2 dependency at 36 wks post-menstrual age) are diseases of prematurely born infants exposed to mechanical ventilation and/or oxygen supplementation. In order to determine whether genetic variants of surfactant proteins (SPs-A, B, C, and D) and SP-B-linked microsatellite markers are risk factors in BPD, we performed a family based association study using a Greek study group of 71 neonates (<30 wks gestational age) from 60 families with, 52 BPD_28D and 19 BPD_36W, affected infants. Genotyping was performed using newly designed pyrosequencing assays and previously published methods. Associations between genetic variants of SPs and BPD subgroups were determined using Transmission Disequilibrium Test (TDT) and Family Based Association Test (FBAT). Significant associations (p ≤ 0.01) were observed for alleles of SP-B and SP-B-linked microsatellite markers, and haplotypes of SP-A, SP-D, and SP-B. Specifically, allele B-18_C associated with susceptibility in BPD_36W. Microsatellite marker AAGG_6 associated with susceptibility in BPD_28D/36W group. Haplotype analysis revealed ten susceptibility and one protective haplotypes for SP-B and SP-B-linked microsatellite markers and two SP-A-SP-D protective haplotypes. The data indicate that SP loci are linked to BPD. Studies in different study groups and/or of larger sample size are warranted to confirm these observations and delineate genetic background of BPD subgroups.

The relationship between hirudin and activated clotting time: Implications for patients with heparin-induced thrombocytopenia undergoing cardiac surgery

Anticoagulation with recombinant hirudin (r-hirudin) (Refludan™) has been suggested as an alternative to heparin for patients with heparin-induced thrombocytopenia requiring cardiac surgery. We sought to develop a modified activated coagulation time (ACT) that would allow quantification of the levels of r-hirudin required during cardiopulmonary bypass (CPB). Twenty-one patients scheduled for elective cardiac surgical procedures requiring CPB were enrolled in this IRB-approved study. R-hirudin was added to blood specimens obtained before heparin administration (before CPB) and 30 min after heparin neutralization with protamine (after CPB) to result in concentrations of 0, 2, 4, 6, 7, or 8 &mgr;g/mL. Kaolin/ACT and complete blood count measurements were assayed in native specimens (first 10 patients, Phase I) or in specimens mixed with equal volumes of commercial normal plasma (second 11 patients, Phase II). In Phase I, good (r2 = 0.83) linear relationships between ACT values and r-hirudin concentrations (≤4 &mgr;g/mL) were observed in specimens obtained before CPB. However, ACT values were markedly prolonged (P < 0.0001) by r-hirudin in specimens obtained after CPB, with ACT values generally exceeding the ACT’s detection limit (>999 s) at hirudin concentrations >2 &mgr;g/mL. In patient specimens mixed with normal plasma (Phase II), ACT/hirudin relationships (i.e., hirudin/ACT slope values obtained with hirudin concentration ≤4 &mgr;g/mL) in the post-CPB period (0.022 ± 0.004 &mgr;g · mL−1 · s−1) were similar (P = 0.47) to those (0.019 ± 0.004 &mgr;g · mL−1 · s−1) obtained in the pre-CPB period. Accordingly, a significant relationship between normal plasma-supplemented ACT values and predilution hirudin concentration was obtained in the post-CPB (hirudin = 0.039ACT − 4.34, r2 = 0.91) period. Although our data demonstrate that the ACT test cannot be used to monitor hirudin during CPB, the addition of 50% normal plasma to post-CPB hemodiluted blood specimens yields a consistent linear relationship between hirudin concentration and ACT values up to a predilution concentration of 8 &mgr;g/mL. Plasma-modified ACT may be useful in monitoring hirudin anticoagulation during CPB.

Catheter ablation of hemodynamically unstable ventricular tachycardia with mechanical circulatory support

BACKGROUND Catheter ablation of hemodynamically unstable ventricular tachycardia (VT) is possible with mechanical circulatory support (MCS), little is known regarding the relative safety and efficacy of different supporting devices for such procedures. METHODS AND RESULTS Sixteen consecutive patients (aged 63 ± 11 years with left ventricular ejection fraction of 20 ± 9%) who underwent ablation of hemodynamically unstable VT were included in this study. Hemodynamic support included percutaneous (Impella® 2.5, n = 5) and implantable left ventricular assist devices (LVADs, n = 6) and peripheral cardiopulmonary bypass (CPB, n = 5). Except for 2 Impella cases, hemodynamic support was adequate (with consistent mean arterial pressure of > 60 mmHg) to permit sufficient activation mapping for ablation. In the Impella and CPB groups, mean time under hemodynamic support was 185 ± 86 min, and time in VT was 78 ± 36 min. Clinical VT could be terminated at least once by ablation in all patients except 1 case with Impella due to hemodynamic instability. Peri-procedural complications included hemolysis in 1 patient with Impella and surgical intervention for percutaneous Impella placement problems in another 2. The median number of appropriately delivered defibrillator therapies was significantly decreased from 6 in the month before VT ablation to 0 in the month following ablation (p = 0.001). CONCLUSIONS Our data suggest that peripheral CPB and implantable LVAD provide adequate hemodynamic support for successful ablation of unstable VT. Impella® 2.5, on the other hand, was associated with increased risk of complications, and may not provide sufficient hemodynamic support in some cases.

Acute left atrial thrombus after recombinant factor VIIa administration during left ventricular assist device implantation in a patient with heparin-induced thrombocytopenia.

We present a patient with end-stage heart failure and heparin-induced thrombocytopenia Type II, who required cardiopulmonary bypass (CPB) during a repeat implantation of a left ventricular assist device for long-term circulatory support. Bivalirudin was selected for anticoagulation during CPB, with concomitant infusion of aprotinin, in an effort to ameliorate blood loss. Nonetheless, profuse bleeding after CPB required massive transfusion of packed red blood cells, multiple coagulation factors, and platelets. Because of persistent bleeding, a single dose of recombinant factor VIIa (rFVIIa, 7.2 mg) was administered as rescue therapy. Within minutes, a large left atrial thrombus was detected by transesophageal echocardiography. We believe this is the first documentation of acute left atrial thrombus formation immediately after a single dose of recombinant factor VIIa administration during a left ventricular assist device implantation.

Antiischemic effects of nicardipine and nitroglycerin after coronary artery bypass grafting

BACKGROUND We assessed the efficacy of a continuous infusion of nicardipine and nitroglycerin in reducing the incidence and severity of perioperative myocardial ischemia during elective coronary artery bypass grafting procedures in a prospective, randomized, controlled study. METHODS Patients received either nicardipine infusion (0.7 to 1.4 microg x kg(-1) x min(-1); n = 30) or nitroglycerin (0.5 to 1 microg x kg(-1) x min(-1); n = 30) or neither medication (n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes (MIE) were considered to have occurred with ST-segment depressions or elevations of at least 1 mm and at least 2 mm (for both depressions or elevations), each at J + 60 ms and lasting at least 1 minute, using a two-channel Holter monitor. RESULTS Only nicardipine significantly decreased the duration (p = 0.02) of the 1-mm or greater minutes per hour (3.2 +/- 1.2 minutes per hour) and eliminated the number (p = 0.02) of the 2-mm or greater minutes per hour (zero minutes per hour) when compared with control patients (17.2 +/- 5.6 minutes per hour and 0.17 minutes per hour, respectively) during the intraoperative postbypass period. CONCLUSIONS Our results suggest that nicardipine lessened the severity of myocardial ischemia shortly after coronary revascularization and could be considered as an alternative to standard antiischemic therapy.

Pulmonary artery catheter for coronary artery bypass graft: does it harm our patients? Primum non nocere.

Bedside balloon flotation pulmonary artery catheters (PAC) were introduced in 1970 by Drs. Swan and Ganz. Shortly thereafter, PACs became a core component of managing critically ill patients and patients undergoing cardiac surgery. PACs are used for diagnostic and monitoring purposes, and generate detailed information about cardiac filling pressures, cardiac output, and mixed venous oxygen saturation. The availability of these data has generally been believed to allow for hemodynamic optimization of patients that ultimately improve patient outcome. In the mid 1980s, studies questioned the benefit and even raised concern about the danger of PACs, leading some to recommend their abandonment. This concern was brought to a zenith by the landmark observational study by Connors et al. that found an increased mortality associated with use of PACs in patients admitted to intensive care units (ICU). This led to the conduct of several fairly large randomized controlled trials that did not confirm an increased mortality associated with use of PACs, but also did not find benefit with their usage. However, the latter studies did not address PAC use in patients undergoing cardiac surgery. Other studies, though, have challenged the universal need for and safety of PACs in patients undergoing coronary artery bypass graft (CABG) surgery. Nonetheless, PACs continue to be widely used, often routinely, in a large number of surgeries despite lack of strong evidence of their benefit. The risk–benefit calculation of PAC use in cardiac surgery patients has become particularly pressing in recent years, with the availability of new, less invasive technologies including transesophageal echocardiography (TEE) and less invasive methods for cardiac output monitoring. Thus, clinicians caring for patients undergoing cardiac surgery are left with conflicting and incomplete data on which to base their decision on PAC use in individual patients. In this issue of Anesthesia & Analgesia, Schwann and colleagues present the findings of a prospective, observational study on the effect of PAC use on fatal and nonfatal outcomes in 5065 patients who underwent CABG surgery at 70 international centers between November 1996 and June 2000. The authors report that PAC use was associated with a 68% greater risk of the composite outcome of death (any cause), or cardiac, cerebral, or pulmonary dysfunction in comparison with non-PAC use. Patients monitored with a PAC suffered twice the risk for all-cause mortality (3.5% vs 1.7%) and a similarly increased rate of adverse cardiac, cerebral, and renal outcomes. Patients who had PACs received inotropic drugs more frequently, received larger volumes of IV fluids after surgery, and experienced longer time to tracheal extubation and longer hospitalization in the ICU than did those who did not have PACs placed during surgery. How should this study impact the current approach to perioperative care for patients undergoing CABG surgery? First, let us review the strengths of this paper. It included a large patient sample size undergoing surgery under “realworld” clinical practices, and it included patients from a diverse cross-section of centers around the world. This aspect of the study would support the external validity of the study. At the same time, the study has numerous weaknesses that are mostly acknowledged by the authors. For example, the data presented are 10 years old, which begs the question of their relevance to current clinical practice given advances in knowledge, technology, and alternative monitoring approaches. An important limitation of this study is the fact that the study was observational, relying on propensity analysis to provide matched groups. Propensity scoring, like logistic regression analysis, is a way to adjust a comparison between groups that differ at baseline in some characteristic. Propensity scoring has the advantage of being able to adjust simultaneously for many characteristics in an attempt to generate a control group at equal risk for receiving a PAC (even when they did not). The authors chose 36 covariates to estimate the propensity scores but left out important covariates, including preoperative drug therapy ( -blockers, statins, antihypertensive agents, aspirin, diabetic agents) and participating institution. The latter is particularly troublesome given that the rate of PAC insertion varied from 1% to 99% among centers, suggesting differences among institutions not accounted for in the From the *Department of Anesthesiology, University of Kentucky College of Medicine, Lexington; and †Department of Anesthesiology, University of Minnesota, Minneapolis. Accepted for publication July 11, 2011. Funding: None. The authors declare no conflict of interest. Reprints will not be available from the authors. Address correspondence to Eugene A. Hessel, MD, University of Kentucky College of Medicine, 800 Rose St., Lexington KY 40536. Address e-mail to ehessel@uky.edu. Copyright

Paravertebral Catheter Use for Postoperative Pain Control in Patients After Lung Transplant Surgery: A Prospective Observational Study

OBJECTIVE Effective postoperative pain management has been shown to be a positive predictive factor for postoperative recovery following a thoracotomy. The primary objective of this study was to examine the efficacy and safety of continuous paravertebral blockade in managing acute postsurgical pain following unilateral and bilateral single-lung transplantation. DESIGN The authors conducted a prospective observational trial of patients. SETTING The study was conducted in an academic university hospital. PARTICIPANTS Patients (≥18 years of age) who underwent either unilateral or bilateral single-lung transplantation and received a postoperative paravertebral catheter. INTERVENTIONS Paravertebral catheters were placed via an ultrasound-guided technique on either postoperative day 1 or 2. After placement, a continuous infusion of 0.2% ropivacaine was run at 0.2 to 0.25 mL/kg/h with maximum dose of 7 mL/h per side in bilateral lung transplant patients, and 14 mL/h in unilateral lung transplant patients. MEASUREMENTS AND MAIN RESULTS Patients were followed up to 120 hours after placement of catheters, and pain scores, opioid use, and adverse events were recorded. There were 35 patients who completed the study from October 2013 to December 2014 (21 bilateral transplants and 14 unilateral transplants). The mean time to paravertebral catheter placement was 1.14 days in the overall group, with median time to extubation occurring 543 minutes after placement (range, 23-2,985 minutes). Catheters remained in place for a mean of 7.18 days. The mean maximal pain scores for both groups was 5.94 (day 1), 6.26 (day 2), 6.20 (day 3), 5.12 (day 4), and 5.60 (day 5). There were no adverse events related to the paravertebral catheters in either group. CONCLUSIONS Paravertebral catheters provide a feasible option for postoperative pain control following unilateral or bilateral single-lung transplant in adult patients. Future research should focus on randomized trials of thoracic epidurals compared to paravertebral catheters.

Effects of nicardipine and nitroglycerin on perioperative myocardial ischemia in patients undergoing coronary artery bypass surgery.

Perioperative myocardial ischemic episodes are predictive of adverse cardiac outcomes after coronary artery bypass surgery. We compared the efficacy of continuous infusions of nicardipine (group NIC) and nitroglycerin (group NTG) in reducing the frequency and severity of myocardial ischemic episodes. Patients received either a nicardipine infusion, 0.7 to 1.4 microg/kg/min (n = 30), nitroglycerin infusion, 0.5 to 1 microg/kg/min (n = 30), or neither medication (group C; n = 17) after aortic occlusion clamp release and for 24 hours postoperatively. Myocardial ischemic episodes were considered as ST segment depressions or elevations of 1 mm or greater from baseline, each at J + 60 milliseconds and lasting 1 minute or greater, using a two-channel Holter monitor. Only nicardipine significantly decreased the duration (3.2 +/- 1.2 min/h) and the area under the ST time curve (AUC; 5.7 +/- 15.7 AUC/h) of 1-mm or greater myocardial ischemic episodes compared with group C (17.2 +/- 5.6 min/h and 30.1 +/- 49 AUC/h, respectively) during the intraoperative postbypass period. A trend toward lower frequency, duration, and area under the ST time curve of myocardial ischemic episodes was observed in group NIC compared with group NTG. Cardiac indices and mixed venous oxygen saturations were significantly greater, whereas systemic pressures were less in group NIC compared with group NTG for the same period. These results suggest that nicardipine, but not nitroglycerin, decreased the duration and area under the ST time curve of myocardial ischemic episodes shortly after coronary revascularization. Larger studies are required to verify the efficacy of nicardipine in reducing the severity of myocardial ischemia during cardiac surgery.

Echocardiographic Characterization of Left Ventricular Diastolic Properties in Patients Presenting for the Maze Procedure

The aim of this study is to characterize and compare the left ventricular (LV) diastolic filling patterns in patients with paroxysmal (PAF) versus chronic atrial fibrillation (CAF) undergoing the maze procedure and to examine their relation with the hemodynamic status. Fifty patients with PAF and 22 with CAF were studied. Hemodynamic measurements and transesophageal echocardiography (TEE) were performed after the induction of anesthesia but before surgical incision, at stable conditions. Transmitral (TMF) and pulmonary venous flow (PVF) velocities were recorded with the pulsed Doppler method. Statistical analysis between the two groups (PAF and CAF) was performed using Students t-test and chi-squared test, with P less than .05 statistically significant. Compared with patients in the PAF group, those in the CAF group had: (1) higher pulmonary capillary wedge pressure (14 +/- 5 v 12 +/- 4 mm Hg; P < .05), (2) lower left ventricular fraction of area change (43% +/- 6% v 52% +/- 9%; P < .01), (3) slower PVF systolic wave velocity (23 +/- 10 v 35 +/- 15 cm/s; P < .05), and (4) lower ratio of PVF systolic to diastolic wave velocity (0.75 +/- 0.3 v 1.2 +/- 0.4; P < .05). In the present study, LV filling patterns of abnormal relaxation were found in all our patients who underwent the maze procedure for CAF or PAF. Although the cause of LV filling abnormalities is not apparent, the data suggest LV diastolic dysfunction is prevalent in these patients.