Journal of Cardiothoracic and Vascular Anesthesia

Published by WB Saunders
Print ISSN: 1053-0770
Publications
The pharmacokinetics of ropivacaine 0.2% were evaluated during a 48-hour continuous extrapleural infusion with 2 different infusion rates in patients undergoing cardiovascular surgery. The hypotheses that no toxic plasma concentrations of ropivacaine would be reached and that proportionality exists among plasma concentrations and dosage used were tested. A prospective, randomized, nonblinded study. The investigation was performed as a single-center study in the Division of Cardiovascular Anesthesia, University Hospital of Zurich, in Switzerland. Seventeen consenting adults scheduled for elective cardiovascular surgery, with or without extracorporeal bypass, via the lateral thoracotomy approach were enrolled. For postoperative pain relief, patients were randomly assigned to receive continuous extrapleural infusion of ropivacaine 0.2% at a rate of either 6 or 9 mL/h over 48 hours. Plasma concentrations of ropivacaine reached toxic levels (>2.2 mg/L) in 25% of cases. No proportionality of plasma concentrations of ropivacaine existed when the 2 dosing regimens were compared. Plasma concentrations of ropivacaine, administered at the given dose and rates during continuous extrapleural infusion, are unpredictable and may reach toxic levels in patients undergoing major cardiothoracic surgery.
 
This study was designed to determine whether ropivacaine plus fentanyl was as effective as bupivacaine plus fentanyl in a continuous thoracic paravertebral block after posterolateral thoracotomy. Patients were randomly assigned in a blinded fashion to receive 1 of 2 solutions for paravertebral analgesia. Multi-institutional university hospital. Sixty patients undergoing elective thoracotomy. Interventions: A continuous paravertebral infusion of 0.1 mL/kg/h of either 0.3% ropivacaine/fentanyl, 3 microg/mL, or 0.25% bupivacaine/fentanyl, 3 microg/mL, was started on admission to the intensive care unit. Pain scores (rest, deep breathing, and coughing), spirometry, subcutaneous opioids, or nonsteroidal anti-inflammatory drug consumption and adverse events were assessed for 48 hours. Both techniques provided adequate pain relief for the first 2 days after posterolateral thoracotomy. There were no differences between groups in pain scores at rest, coughing, or movement. There was an improvement of spirometry values between the first and second day in both groups. There were no differences in the requirements for rescue analgesia and side effects between groups. It is concluded that both bupivacaine, 0.25%, and ropivacaine, 0.3%, with fentanyl are equally effective for post-thoracotomy pain control when used via continuous paravertebral blockade.
 
To compare transfusion requirements in adult cardiac surgery patients when balanced hydroxyethyl starches (HES) (130/0.4) or balanced crystalloids is used for pump prime and intraoperative fluid therapy. Data were obtained retrospectively from medical records and perfusion charts. Matching based on propensity scores was used to adjust for potential confounders. A university hospital. Adult patients undergoing cardiac surgery with the use of cardiopulmonary bypass. Allocation to one of the study groups according to whether balanced HES or balanced crystalloids was used for pump prime and intraoperative fluid therapy. 240 propensity-matched patients were retained for final analyses. Forty-eight patients (40%) of the colloid group and 28 patients (23.3%) of the crystalloid group received blood products, with an odd ratio (95% CI) of 2.1(1.2-3.8 (P = 0.009). After bypass HES patients had lower haemoglobin levels (8.4 [1.3] gr/dL vs 9.6 [2] gr/dL; P<0.001) and a higher cumulate chest drain output after 3 hours (180 [210] mL vs 140 [100] mL, P<0.001]. Heparinase thromboelastogram (TEG(®)) showed longer K times (2.5[1.1] vs 1.6[0.8], P<0.001) and lower maximal amplitudes (55.1[12.5] vs 63.4[9.8], P = 0.008). HES patients required more transfusions, owing to greater hemodilution, HES-induced clotting disturbances, and bleeding. Copyright © 2014 Elsevier Inc. All rights reserved.
 
To compare volume therapy with HES 130/0.4, a new hydroxyethylstarch (HES) solution with a gelatin-based fluid replacement strategy. Prospective, randomized, safety study. Urban, university-affiliated hospital (single institution). Forty-two patients undergoing elective cardiac surgery. Patients were prospectively randomized into 2 groups: In group 1 (n = 21), gelatin was given perioperatively for volume support until the 1st postoperative day to keep the central venous pressure (CVP) between 10 and 14 mmHg; in group 2 (n = 21) HES 130/0.4 was administered using the same protocol as in group 1. Standard coagulation variables and modified thromboelastography (TEG) were used. Using different activators for extrinsic and intrinsic activation and heparin inactivation by heparinase, the onset of coagulation (coagulation time), kinetics of clot formation (clot formation time), and maximum clot firmness were measured. Measurements were performed after induction of anesthesia (T0), at the end of surgery (T1), 4 hours after surgery (T2), and on the morning of the 1st postoperative day (T3). A total of 3310 +/- 810 mL of gelatin and 3070 +/- 570 mL of HES 130/0.4 were used in the 2 groups during the study period. The 2 groups did not differ with regard to postoperative bleeding or in use of packed red blood cells or fresh frozen plasma. Standard coagulation variables were similar between the 2 groups. All TEG variables were within the normal range at baseline. Coagulation time and clot formation time data were significantly elevated after surgery and in the intensive care unit, without showing specific differences between the 2 volume replacement groups. Intrinsic TEG and heparinase TEG clot formation times remained significantly higher until the end of the study period. No differences were seen between HES-treated and gelatin-treated patients. Volume replacement with the new HES preparation was as safe as gelatin-based volume replacement with regard to coagulation in cardiac surgical patients. HES 130/0.4 is an alternative plasma substitute to treat volume deficits.
 
The time course of base excess; squares, HES balanced; triangles, HES saline; data are means standard deviation; **p < 0.01 and ***p < 0.001 for differences between groups; baseline, after anesthesia induction; T1, during extracorporeal circulation (p < 0.0001); T2, after extracorporeal circulation (p 0.0037); T3, end of surgery (p 0.0032); T4, 1 hour after arrival at ICU (p 0.0005); T6, first postoperative morning (p 0.0039); p values are results of analysis of covariance-based testing for the superiority of HES 130 balanced with the factors centre, treatment, and baseline (see Methods section for further details).
Patient Characteristics
The infusion of large amounts of saline-based solutions may contribute to the development of hyperchloremic metabolic acidosis and the use of a balanced carrier for colloid solutions might improve postoperative acid-base status. The equivalence of 2 hydroxyethyl starch (HES) solutions and the influence on chloride levels and acid-base status by selectively changing the carrier of rapidly degradable modern 6% HES 130/0.4 were studied in cardiac surgery patients. A prospective, randomized, double-blinded study. A clinical study in 2 cardiac surgery institutions. Eighty-one patients. Patients received either 6% HES130/0.4 balanced (Volulyte; Fresenius Kabi, Bad Homburg, Germany) or 6% HES130/0.4 saline (Voluven; Fresenius Kabi, Bad Homburg, Germany) for intra- and postoperative hemodynamic stabilization. The therapeutic equivalence of both HES formulations regarding volume effect and superiority of the balanced electrolyte solution regarding serum chloride levels and acid-base status were measured. Similar volumes of both HES 130/0.4 balanced and HES 130/0.4 saline were administered until 6 hours after surgery, 2,391 ± 518 mL in the HES 130/0.4 balanced group versus 2,241 ± 512 mL in the HES 130/0.4 saline group. The 95% confidence interval for the difference between treatments (-77; 377 mL; mean, 150 mL) was contained entirely in the predefined interval (-500, 500 mL), thereby proving equivalence. The serum chloride level (mmol/L) was lower (p < 0.05 at the end of surgery), and arterial pH was higher in the balanced group at all time points except baseline, and base excess was less negative at all time points after baseline (p < 0.01). Volumes of HES needed for hemodynamic stabilization were equivalent between treatment groups. Significantly lower serum chloride levels in the HES balanced group reflected the lower chloride load of similar infusion volumes. The HES balanced group had significantly less acidosis.
 
Cardioprotective properties have been shown with halogenated volatile agents. It was hypothesized that low-dose isoflurane administered before aortic cross-clamping may reduce the amount of dobutamine required to improve impaired postoperative cardiac function after various types of cardiac surgery. A prospective, randomized trial. An anesthesia and intensive care unit, university hospital. Two hundred eighty cardiac surgery patients. All patients allocated to either isoflurane treatment (T) or no treatment (control group [C]) received total intravenous anesthesia. In the treatment group, isoflurane was administered at a 0.5 minimum alveolar concentration (MAC) from tracheal intubation to initiation of cardiopulmonary bypass (CPB). During weaning from CPB, dobutamine was introduced by using a hemodynamically driven decision tree. The number of patients receiving dobutamine was comparable (66 v 78, p = 0.07, in T and C groups, respectively). The total amount of postoperative dobutamine indexed to patient weight, considered as the primary endpoint, was reduced in the isoflurane-treated group (4.2 +/- 8 v 7.2 +/- 15, p < 0.02, in T and C, respectively). Isoflurane was identified as an independent variable significantly (odds ratio [confidence interval]) influencing the total amount of postoperative dobutamine (0.53 [0.31-0.92], p < 0.02). Postoperative troponin I release at 20 hours was not affected by isoflurane treatment. This study revealed that exposure to 0.5 MAC isoflurane before CPB reduced the total amount of dobutamine required to normalize postoperative cardiac dysfunction in various types of cardiac surgical patients.
 
To compare the effects of hypertonic (7.5%) saline (HS), normal (0.9%) saline (NS), and 6% hydroxyethyl starch (HES) on extracellular fluid volumes in the early postoperative period after cardiopulmonary bypass. A prospective, randomized, double-blind study. University teaching hospital. Forty-eight patients scheduled for elective coronary artery bypass graft surgery. Patients were randomly allocated to receive 4 mL/kg of HS, NS, or HES during 30 minutes when volume loading was needed during the postoperative rewarming period in the intensive care unit. Plasma volume was measured using a dilution of iodine-125-labeled human serum albumin. Extracellular water and cardiac output were measured by whole-body impedance cardiography. Plasma volume had increased by 19 +/- 7% in the HS group and by 10 +/- 3% in the NS group (p = 0.001) at the end of the study fluid infusion. After 1-hour follow-up time, the plasma volume increase was greatest (23 +/- 8%) in the group receiving HES (p < 0.001). The increase of extracellular water was greater than the infused volume in the HS and HES groups at the end of the infusion. One-hour diuresis after the study infusion was greater in the HS group (536 +/- 280 mL) than in the NS (267 +/- 154 mL, p = 0.006) and HES groups (311 +/- 238 mL, p = 0.025). The effect of HS on plasma volume was short-lasting, but it stimulated excretion of excess body fluid accumulated during cardiopulmonary bypass and cardiac surgery. HS may be used in situations in which excess free water administration is to be avoided but the intravascular volume needs correction.
 
The purpose of this study was to evaluate the feasibility and safety of immediate extubation (ultrafast-track anesthesia [UFTA]) in the operating room, and the predictors of when not to attempt it in patients undergoing off-pump coronary artery bypass graft surgery (OPCAB). Case series. A private hospital. One thousand one hundred ninety-six patients undergoing OPCAB surgery, representing 4 years of a single anesthesia service's practice (3 anesthesiologists), were evaluated for immediate extubation. All patients were considered amenable to immediate extubation if specific criteria were met. Patients received general anesthesia (UFTA protocol) and underwent off-pump coronary artery bypass graft surgery. One thousand sixty-five patients (89%) met extubation criteria and were extubated successfully in the operating room. By multivariate analysis, the following independent predictors of avoiding immediate extubation were identified: reoperation (odds ratio [OR] = 3.9, p < 0.001), pre-existing renal disease (OR = 3.1, p < 0.0001), diabetes (OR = 1.7, p < 0.007), preoperative intra-aortic balloon pump placement (OR = 7.4, p < 0.0001), and total surgical time (OR = 3.7, p < 0.0001). Patients who met extubation criteria had lower in-hospital reintubation (2.5% v 16%, p < 0.001), myocardial infarction (1.03% v 4.58%, p = 0.001), renal insufficiency (2.2% v 7.63%, p < 0.001), stroke (0.4% v 2.29%, p = 0.032), and mortality rates (1.2% v 10.7%, p < 0.001) than patients who did not. UFTA is feasible and safe in most patients undergoing OPCAB surgery. Baseline and intraoperative data predicted when immediate extubation should not be attempted.
 
To assess the characteristics and prognosis of patients in whom heparin-induced thrombocytopenia (HIT) was confirmed (HIT+) among suspected HIT patients after having cardiac surgery and to assess the accuracy of two HIT scoring systems. An observational prospective study. A cardiac surgery unit of a tertiary center from November 2005 to September 2007. Of the 1,722 patients who underwent cardiac surgery, 63 were suspected of HIT based on a platelet count <100 × 10(9)/L, a decrease in platelet count of >30%, or the occurrence of a thrombotic event. The HIT criteria were as follows: (1) the absence of another cause of thrombocytopenia, (2) positive antiplatelet factor 4 (PF4) antibodies (>0.5 optical density [OD]/mn) on enzyme-linked immunoabsorbent assay, and (3) recovery in platelet count after the discontinuation of heparin and substitution by danaparoid sodium. HIT was confirmed in 24 patients (1.4% [0.8%-1.9%]); 23 belonged to the 984 treated by intravenous unfractionated heparin (IVUH) (2.3% IQ [1.4%-3.3%]) and 1 to the 738 treated by low-molecularweight heparin (0.14% [0.13%-0.4%]) (OD = 17.6; 95% confidence interval, 2.4-131; p < 0.0001). In the HIT+ patients compared with the unconfirmed HIT patients, thrombocytopenia occurred 7 (range, 6-9) days after surgery versus 3 (range, 3-5) days (p < 0.0001), and kinetics of platelet count showed a biphasic pattern. Six HIT+ patients (25% [7.7-42.3]) presented with an arterial thromboembolic event. Diagnosis performances of HIT scoring systems were low. Confirmed HIT occurred predominantly in patients treated with IVUH. The timing of thrombocytopenia and the variation pattern of the postoperative platelet count are key factors in diagnosing HIT. The overall incidence of intracardiac thrombotic events was noted to be high.
 
The purpose of the present investigation was to examine factors influencing resource utilization in patients undergoing on-pump coronary artery bypass graft and off-pump coronary artery bypass (OPCAB) graft surgery at a major university hospital. The resources examined were time to extubation, packed red blood cell (PRBC) transfusion, intensive care length of stay (ICULOS), preoperative and postoperative length of stay (PLOS), and total length of stay (LOS). Observational study of consecutive patients undergoing on- and off-pump coronary artery bypass surgery. Tertiary care cardiac referral center. One thousand seven hundred forty-six consecutive male and female patients undergoing primary coronary artery bypass graft (CABG) surgery over a period of 3 years (1999-2001). Eight hundred eighty-one patients underwent CABG with pump, and 865 patients underwent off-pump coronary artery bypass (OPCAB) surgery. None. The mean time to extubation after surgery was 7.4 hours for on-pump patients and 5.8 hours for the OPCAB group (p<or=0.001); 73.7% of patients on pump received PRBC transfusion as compared with 48.6% of the OPCAB group (p<or=0.001). The mean ICULOS for the on-pump group was 1.6 days and 1.4 days for the OPCAB group (p=0.006). PLOS was 6.5 days for the on-pump group and 5.6 days for the OPCAB group (p<or=0.001). Mean total LOS was 9.7 days for the on-pump group and 8.8 days for the OPCAB group (p<or=0.001). PLOS is correlated with several clinical and demographic ariables. Linear and logistic regression models were used to assess the effects of on/off pump on PLOS. Use of pump is significantly correlated with increased PLOS (p<or=0.001, Kendalls correlation), and pump use is strongly associated with transfusion (odds ratio=2.95, p<or=0.001), which in turn is a determinant of PLOS. There were no significant differences between the on- and off-pump groups in the incidence of postoperative complications except for bleeding requiring reexploration and ventilatory support for more than 72 hours. Incidence of bleeding was 3.3% in the on-pump group and 1.7% in the OPCAB group (p=0.038). In the on-pump group, 3% of patients required >72 hours to postoperative tracheal extubation compared with 1.5% in the OPCAB group (p=0.041). Hospital mortality was 2.7% for the on-pump group and 1.0% for the OPCAB group (p=0.010). The authors found that patients undergoing on-pump CABG have significantly longer time to tracheal extubation, increased blood use, longer ICULOS, PLOS, and total LOS and higher in-hospital mortality, which would translate into significant differences in the expenses associated with these 2 surgical approaches to coronary surgery.
 
The effect of the proteinase-inhibitor aprotinin on blood loss and homologous blood requirement in cardiac surgery was investigated. In a prospective study, 902 adult patients were treated with high-dose aprotinin (total greater than 5 x 10(6) kallikrein inactivator units [KIU]; group A), while 882 patients without aprotinin administration served as the controls (group C). Both groups were operated on between January 1987 and October 1989, and included patients with primary coronary artery bypass grafting (n = 525 group C, n = 560 group A), valve replacement (n = 292 group C, n = 264 group A), or combined procedures (n = 65 group C, n = 78 group A), as well as cardiac reoperations (n = 91 group C, n = 110 group A). The average blood loss 36 hours postoperatively in the aprotinin group was 679 +/- 419 mL, compared with 1,038 +/- 671 mL in the control group (P less than 0.05). Total homologous blood requirement was also significantly less in group A (942 +/- 1,630 mL) compared with group C (1,999 +/- 2,283 mL) (P less than 0.05), a reduction of 53%. Serum creatinine concentrations did not show intergroup differences on the first postoperative day (group A, 1.2 +/- 0.7; group C, 1.3 +/- 0.5 mg/dL) or on discharge from the intensive care unit (ICU). Thus, impairment of renal function as a consequence of aprotinin treatment was not observed. Three patients developed signs of mild circulatory depression after injection of aprotinin, which responded promptly to vasopressor therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 
The purpose of this study was to evaluate the possible cardioprotective effect of sevoflurane versus propofol anesthesia in patients undergoing cardiac surgery. Ten thousand five hundred thirty-five consecutive single cardiac surgical procedures from 3 cardiac centers were reported to a common registry from 1999 to 2005. The registry was established by the National Board of Health, and reporting was obligatory for all public heart centers in Denmark. The patients were stratified according to preoperative risk factors (EuroSCORE parameters). The outcome parameters were 30-day mortality, the incidence of postoperative myocardial infarction, and the incidence of postoperative arrhythmias. Overall, the 30-day mortality was lower after sevoflurane (2.84%) versus propofol (3.30%), although not significantly so (p = 0.18). No difference was found in the incidence of postoperative myocardial infarction (sevoflurane, 7.76%/propofol, 7.47%). Patients with preoperative unstable angina and/or recent myocardial infarction, and thus already "preconditioned," did not show any difference in mortality between anesthetic groups, whereas patients without these predictors showed a lower postoperative mortality after sevoflurane (2.28% v 3.14%, p = 0.015), which can at least partly be explained by a preconditioning-like effect. The data suggest that patients suffering relatively severe preoperative ischemic stress benefited from propofol anesthesia, which can be related to the antioxidant effects of propofol. Patients in the sevoflurane group had a higher incidence of postoperative atrial fibrillation (28.75% v 24.87%, p < 0.001), whereas patients in the propofol group showed a higher incidence of all other arrhythmias. Sevoflurane and propofol both possess some, although different, cardioprotective properties. Sevoflurane appears to be superior to propofol in patients with little or no ischemic heart disease, such as noncoronary artery bypass graft (CABG) surgery and CABG surgery without severe preoperative ischemia, whereas propofol seems superior in patients with severe ischemia, cardiovascular instability, or in acute/urgent surgery.
 
Objectives: In a variety of experimental models, propofol has been shown to protect the brain. It was hypothesized that a clinically achievable high dose of propofol would induce cerebral protective effects in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The authors investigated the effects of different target plasma concentrations of propofol on cerebral injury by measuring serum S-100β protein and neuron-specific enolase (NSE) levels in patients undergoing single-valve replacement with CPB. Design: A prospective, randomized study. Setting: A university hospital. Participants: Forty-two patients undergoing single-valve replacement with CPB. Interventions: Patients were randomly divided into 3 groups (n = 14 each). Each group received a target-controlled infusion of propofol with plasma concentrations of 1.8 μg/mL (low dose, Group-L), 2.4 μg/mL (medium dose, Group-M), or 3.2 μg/mL (high dose, Group-H). The propofol target concentrations were unchanged throughout the surgery. Measurements and main results: In all 3 groups of patients, at all time points after CPB, the plasma S-100β protein and NSE levels, which served as biochemical markers of brain damage, were significantly higher than the preoperative levels (p<0.05). Group-H showed significant decreases in S-100β protein and NSE compared with Group-L (p< 0.05). Conclusion: In the range of commonly used clinical concentrations, administration of a high dose of propofol during CPB attenuated the biochemical markers of brain damage as compared with low-dose propofol anesthesia.
 
Objective: To elucidate the magnitude of global cerebral oxygenation impairment, using cerebral oxygenation indices and S-100β protein as potential markers, during off-pump coronary artery bypass grafting (OPCAB). Design: Prospective cohort study. Setting: Tertiary cardiac center. Participants: Thirty-five patients undergoing OPCAB. Interventions: Jugular bulb and arterial blood samples for cerebral oxygenation indices (arterial oxygen and carbon dioxide partial pressures, jugular bulb oxygen saturation, arterial-jugular bulb oxygen content, arterial-jugular carbon dioxide partial pressure, brain oxygen extraction ratio, and estimated respiratory quotient) and S-100β protein determination were collected at anesthesia induction; anterior, inferior, and posterior wall anastomoses; after sternal closure; and 6 hours postoperatively. Concomitant hemodynamic data were obtained. The S-100β determination was extended to 12 and 24 hours postoperatively. Measurements and main results: Heart positioning for the target vessel exposure induced significant hemodynamic deterioration (p < 0.001). Although cerebral oxygenation indices were influenced adversely by a low-cardiac-output state mainly during vertical heart dislocation (p < 0.001), they remained within normal limits. Hemodynamic and cerebral oxygenation statuses reverted to baseline within 6 hours postoperatively. Similarly, S-100β jugular bulb and arterial protein levels presented a gradual increase, which peaked by the end of surgery (means, 0.54 and 0.62 μg/L, respectively; p < 0.001) and then decreased by the first postoperative day. Jugular bulb-arterial S-100β levels were maximized during posterior wall anastomosis (0.098 μg/L; p < 0.01). Conclusion: Although exposure of the 3 main coronary arteries during OPCAB promotes derangement of the cerebral oxygen indices and S-100β release, this seems to be transient, remains within the near-normal range, and is reversible almost completely 6 hours postoperatively.
 
To establish the S-100beta protein profile during carotid artery surgery to show a possible correlation between postoperative stroke and this biochemical marker. Prospective, nonrandomized study. Departments of anesthesiology, biochemistry, and vascular surgery in a single university hospital. One hundred patients consecutively scheduled for carotid endarterectomy. Postoperative neurologic complications were defined as major, occurrence of a postoperative permanent stroke, or minor, occurrence of a new postoperative transient ischemic attack lasting < 2 hours. Serum samples were obtained before induction, before carotid artery cross-clamping, after declamping, at the end of surgery, during recovery, and on the first postoperative day. Concentrations of S-100beta were analyzed using a commercially available kit (LIA-mat S300 analyzer, Byk-Sangtec Medical, Bromma, Sweden). Ninety-five patients awoke without a neurologic defect. Three patients experienced a permanent stroke, and 2 patients had a transient ischemic attack. S-100 basal values were unrelated to preoperative status, including hypertension, neurologic status, renal function, and degree of the carotid lesion. S-100 concentration increased slightly but significantly at the end of surgery and remained stable until the first postoperative day. S-100 profile during the procedure was independent of the duration of carotid artery cross-clamping and the need for a shunt. S-100 serum level was not significantly different in the patients with a postoperative ischemic event in comparison with the entire group. The S-100 profile was not increased in 2 of 3 patients with a permanent stroke and in 1 of 2 patients with a transient ischemic attack in comparison with the 95 patients with uneventful recovery. S-100 concentration slightly increased at the end of surgery and remained high until the first postoperative day in all patients. S-100 was not significantly different in the patients with postoperative stroke. S-100 did not serve as a marker for postoperative stroke after carotid artery surgery. This fact must be taken into account during further investigations of S-100.
 
In most medical textbooks, a mediastinoscopy is considered an absolute contraindication for a repeat mediastinoscopy. Retrospectively, perioperative data from 101 patients were evaluated in whom repeat mediastinoscopy was performed. The complication rate was 23% in 18 patients; 10% of these were directly related to the surgery. The surgical complications observed were hemorrhage, biopsy of the esophagus, paresis of a recurrent laryngeal nerve, and pneumothorax, which were all treated successfully. The patients receiving a nondepolarizing relaxant had fewer complications than patients given only a single dose of succinylcholine. In this patient population, the mortality rate was zero. This review concludes that an earlier mediastinoscopy is not necessarily an absolute contraindication for repeat mediastinoscopy.
 
To determine if a modern anesthetic approach permits extubation immediately after surgery for single-lung transplantation. A retrospective study of all patients undergoing single-lung transplantation from June 1993 to December 1999 in Denmark. Rigshospitalet, Copenhagen University hospital. One hundred six consecutive patients scheduled for single-lung transplantation. From July 1997, the anesthetic approach was changed to facilitate early extubation. The changes included epidural analgesia and short-acting anesthetic drugs. One hundred six patients were anesthetized for single-lung transplantation. The first 33 patients were moved to the intensive care unit for postoperative mechanical ventilation. After the change of anesthesia technique, 53 of 73 patients were extubated in the operating room. Eleven patients needed reintubation within the first 24 hours because of respiratory insufficiency, pulmonary edema, hemorrhage, or pneumothorax. The need for reintubation increased the length of stay in the intensive care unit by 1 day from 2 to 3 days (NS). The possibility of early extubation or the need for reintubation was not related to age, weight, sex, preoperative condition, mode of transport of the graft, duration of graft ischemia, or side of transplantation. This study has shown that it is possible to extubate patients in the operating room immediately after single-lung transplantation in the majority of cases.
 
The primary objective of this study was to analyze perioperative intra-aortic balloon pump (IABP) insertion in patients undergoing cardiac surgery in the authors' institution from 1995 to 2005 and to propose an explanation for changes in use over this period. A secondary objective was to assess patient variables associated with IABP use. This is a retrospective study including patients who underwent cardiac surgery between 1995 and 2005. The Cardiothoracic Anesthesia Patient Registry of a single teaching institution was queried to obtain the required information. Thirty thousand two hundred sixty-nine cardiac surgery patients. Intra-aortic balloon pump insertion before surgery, after cardiopulmonary bypass, or in the cardiovascular intensive care unit was assessed in patients who underwent isolated coronary artery bypass graft surgery, valve surgery, or both. Select patient variables were analyzed for their association with IABP insertion. Transesophageal echocardiography (TEE) examinations, milrinone use, and mortality rates also were determined. Among 30,269 cardiac surgery patients, 1,310 (4.32%) underwent IABP insertion. Combined preoperative, intraoperative, and postoperative IABP use decreased from 7.8% in 1995 to 3.0% in 2005. Simultaneously, the intraoperative use of milrinone increased from 4.8% to 8.8% and postoperative use increased from 5.2% to 7.8%. The number of intraoperative TEE examinations more than doubled from approximately 1,700 to 3,500. The overall mortality for patients with preoperative, intraoperative, and postoperative IABP insertion was 12.6%, 17.5%, and 47.7%, respectively. From 1995 to 2005, preoperative, intraoperative, and postoperative IABP use decreased by approximately 60% in cardiac surgery patients. Simultaneously, the use of TEE and milrinone each doubled. Although a cause-effect relationship cannot be established from the present study's observational data, the trends coincide and may be related.
 
To investigate the effects of JM-1232(-) on norepinephrine (10(-6) mol/L)- and high K(+) (40 mmol/L)-induced contractions in isolated human gastroepiploic arteries (GEA), and to compare them with the effects of midazolam and propofol. In addition, to investigate whether the benzodiazepine-receptor antagonist, flumazenil, or μ-opioid-receptor antagonist, naloxone, influenced the vascular effects of JM-1232(-). An in vitro experimental study. University laboratory. GEA segments were used from 69 patients undergoing coronary artery bypass graft surgery. JM-1232(-) produced dose-dependent relaxation effects in the rings. Although these effects of JM-1232(-) were greater than those of midazolam and propofol at high concentrations (10(-5)-10(-4) mol/L), there were no significantly different relaxation effects at the clinical concentrations of 3 × 10(-6) mol/L JM-1232(-), 3 × 10(-6) mol/L midazolam, and 1 × 10(-5) mol/L propofol. In addition, all these effects were independent of the presence of a functional endothelium. Vasorelaxation induced by JM-1232(-) on norepinephrine-preconstricted GEA was inhibited by flumazenil, but not by naloxone. These results indicate that JM-1232(-) dose-dependently relaxes smooth muscle in human GEA, this effect being independent of the endothelium. Within the ranges of plasma concentrations achieved in clinical practice, JM-1232(-) had similar vasorelaxation effects to midazolam and propofol. JM-1232(-)-induced vasorelaxation was inhibited by flumazenil, indicating that JM-1232(-)-induced vasorelaxation occurred via peripheral benzodiazepine receptor activation in the GEA.
 
To describe differences in intra- and postoperative care between general (GA) and local/regional anesthesia (LRA) in consecutive high-risk patients with aortic stenosis who underwent transfemoral transcatheter aortic valve implantation (TAVI). A retrospective review of data collected in an institutional registry. An academic hospital. One hundred twenty-five consecutive patients with severe aortic stenosis who underwent transfemoral TAVI. GA versus LRA followed by postoperative care. Complications were defined by pre-established criteria. Consecutive patients referred for transfemoral TAVI between October 2006 and October 2010 initially underwent GA (n = 91) followed by LRA after March 2010 (n= 34). Results are presented as mean ± standard deviation or median (25-75 percentiles) as appropriate. GA and LRA TAVI patients had similar preoperative characteristics. LRA was associated with a significantly shorter procedure duration (LRA: 80 [67-102]; GA: 120 [90-140 minutes]; p < 0.001), hospital stay (LRA: 8.5 [7-14.5]; GA: 15.5 [10-24] days; p < 0.001), intraoperative requirements of catecholamines (LRA 23%; GA: 90% of patients; p < 0.001), and volume expansion (LRA: 11 [8-16]; GA: 22 [15-36] mL/kg; p < 0.001). There were significant differences in delta creatinine (day 1, preoperative creatinine values; LRA: 0 [-12 to 9]; GA: -15 (-25 to 2.9) μmol, p < 0.004). The frequency of any postoperative complications was 38% (LRA) and 77% (GA) (p = 0.11). Thirty-day mortality was 7% (GA) and 9% (LRA) (p = 0.9). This observational study suggests that LRA was associated with less intraoperative hemodynamic instability and significant shortening of the procedure and hospital stay. Changes in the anesthetic technique adapted to changes in TAVI interventional techniques and did not increase the rate of postoperative complications.
 
To examine whether a thromboxane receptor antagonist, NT-126, or a thromboxane synthase inhibitor, OKY-046, prevents circulatory changes caused by protamine reversal of heparin and to evaluate the significance of thromboxane generation in the phenomena. Prospective, randomized, controlled, animal study. A university research laboratory. Twenty-four adult mongrel dogs. According to the pretreatments, the animals were divided into 3 groups (n = 8 in each): (1) control (normal saline); (2) NT-126, 0.01 mg/kg; and (3) OKY-046, 1 mg/kg. Under general anesthesia, all animals were anticoagulated with intravenous heparin, 200 IU/kg, 5 minutes before the pretreatment. Five minutes after the pretreatment, protamine sulfate, 2 mg/kg, was administered intravenously over 10 seconds. Hemodynamic variables were recorded repeatedly until 60 minutes after the protamine. Plasma thromboxane B2 level was determined at baseline and 10 minutes after protamine injection. The average values of mean arterial blood pressure and mean pulmonary artery pressure among the 3 groups in each period and values in each group over the study period were not significantly different. There was weak correlation between maximum percent increases in systolic pulmonary artery pressure or maximum percent decreases in systolic arterial blood pressure for 5 minutes after the protamine versus percent increases in plasma thromboxane B2 level. Neither NT-126 nor OKY-046 appears to be effective in preventing protamine-induced circulatory changes in this dog model, suggesting that thromboxane generation alone is not responsible for the phenomena.
 
To determine whether plasma interleukin (IL)-4, IL-10, and IL-13 concentrations are associated with complications after coronary artery bypass graft (CABG) surgery with cardiopulmonary bypass (CPB). Prospective descriptive study. University teaching hospital. Thirty-two patients during and 24 hours after CABG surgery. Hemodynamic measurements and blood samples were obtained from 32 patients during and after surgery. Coagulation, pulmonary, and cardiovascular functions were specifically assessed during the first 24 hours postoperatively. Plasma IL-4 and IL-13 levels remained unchanged during CABG surgery. In contrast, plasma IL-10 concentrations increased by 117-fold in the immediate postoperative period and returned to pre-CPB values by 24 hours postoperatively. Plasma IL-10 levels were not different in patients with or without cardiovascular impairment, coagulation disorders, and lung injury. Plasma IL-10 levels did not correlate with the leukocyte count, the amount of catecholamines infused, or the duration of CPB. The present results suggest that the development of post-CABG surgery complications might be linked to an insufficient production of anti-inflammatory cytokines, such as IL-4, IL-10, or IL-13, which are unable to counteract the overproduction of inflammatory cytokines.
 
To determine whether patients receiving pegorgotein preoperatively would be less likely than patients receiving placebo to demonstrate postoperative cerebral or myocardial dysfunction and thus would be less likely to (1) demonstrate a decline in neuropsychologic testing after cardiopulmonary bypass, (2) receive inotropic drug support, or (3) demonstrate electrocardiographic signs of ischemia or infarction. Prospective, randomized, blinded clinical trial. University teaching hospital and clinics. Sixty-seven patients with normal left ventricular function undergoing elective, primary coronary artery bypass surgery. Six to 18 hours before aortic cross-clamping, patients received a single dose of placebo (n = 22); pegorgotein, 2,000 IU/kg intravenously (n = 23); or pegorgotein, 5,000 IU/kg intravenously (n = 22). Patients in the three groups were similar; the mean ages were 65, 66, and 67 years, and there were seven, eight, and seven women in the placebo; pegorgotein, 2,000 IU/kg; and pegorgotein, 5,000 IU/kg groups. Fifty-one of 67 patients demonstrated neuropsychologic deficit 5 to 7 days postoperatively (n = 17, 19, and 15 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Median duration of cardiopulmonary bypass was longer in patients with two or more deficits at 4 to 6 weeks than in those with fewer than two deficits (121 v. 98 minutes; p = 0.04). No patient demonstrated a perioperative stroke. Twenty-seven patients required inotropic drug support after cardiopulmonary bypass (n = 8, 11, and 8 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = NS). Inotropic drug support was associated with history of angina (p = 0.01) and increasing weight (p = 0.03). Nine patients demonstrated early postoperative ischemia or infarction (n = 1, 7, and 1 for placebo, 2,000 IU/kg, and 5,000 IU/kg; p = 0.07). This study showed no positive influence of pegorgotein on the incidence of any of the findings and showed a trend toward an increased incidence of myocardial ischemia or infarction.
 
To compare continuous insulin infusion (CII) and intermittent subcutaneous insulin therapy for preventing supraventricular tachycardia. The authors propose that continuous insulin therapy is more effective to reduce supraventricular tachycardias. A prospective randomized study. This study was performed in 2 different centers between April 2005 and February 2007: Gülhane Military Medical Academy and University of Süleyman Demirel. Two hundred diabetic patients were included in this prospective randomized study. Patients were divided into 2 groups according to their insulin therapy in 2 different centers. Group 1 included 100 diabetes mellitus (DM) patients, and CIIs were administrated. These patients received a CII infusion titrated per protocol in the perioperative period (Portland protocol). Group 2 also included 100 DM patients, and subcutaneous insulin was injected every 4 hours in a directed attempt to maintain blood glucose levels below 200 mg/dL. Sliding scale dosage of insulin was titrated to each patient's glycemic response during the prior 4 hours. There were 5 hospital mortalities in the intermittent insulin group. The causes of death were pump failure in 3 patients and ventricular fibrillation in 2 patients. There were 2 hospital mortalities in the CII group (p = 0.044). Thirty-six patients in the intermittent insulin group and 21 patients in the CII group required positive inotropic drugs after cardiopulmonary bypass (p = 0.028). Low cardiac output developed in 28 and 16 patients in the intermittent and CII groups, respectively (p = 0.045). Univariate analysis identified positive inotropic drug requirement (p = 0.011, odds ratio [OR] = 3.41), ejection fraction (EF) (p = 0.001, OR = 0.92), cross-clamp time (p = 0.046, OR = 0.97), left internal mammary artery (p = 0.023, OR = 0.49), chronic obstructive pulmonary disease (COPD) (forced expiratory volume in 1 second <75% of predicted value (p = 0.009, OR = 2.02), intra-aortic balloon pump (p = 0.045, OR = 1.23), body mass index (p = 0.035 OR = 5.60), and CII (p < 0.001, OR = 0.36) as predictors of SVT. Stepwise multivariate analysis confirmed the significance of some of the previously mentioned variables as predictors of SVT. The value of -2 log likelihood of multivariate analyses was 421.504. These were EF (p < 0.001, OR = 0.91), positive inotropic drug requirement (p < 0.001, OR = 3.94), COPD (p = 0.036, OR = 2.11), and CII (p < 0.001, OR = 0.19). Continuous insulin therapy in the perioperative period reduces infectious complications, such as sternal wound infection and mediastinitis, cardiac mortality caused by pump failure, and the risk of development of supraventricular tachycardias.
 
In order to gain insight into the pathophysiology of cerebral ischemia, the focus is on the discrete compartmentalization of neurons and the exquisite homeostasis of the neurochemical, ionic, and molecular environment within these compartments. This review looks at excitotoxic mechanisms of cerebral ischemia spatially by separating presynaptic and postsynaptic events as well as temporally by separating early and late events. Drugs that target these events in the excitotoxic cascade are presented and discussed as potential therapeutic interventions for cerebral ischemia. Despite a better understanding of the mechanisms of cerebral ischemia through a myriad of animal model studies with various "neuroprotective" compounds, the challenge remains to apply this knowledge to the development of compounds that demonstrate neuroprotective efficacy in terms of quality-of-life outcomes in humans.
 
The records of 10 patients who had well-preserved respiratory and ventricular function and had received 50 micrograms of sufentanil and 0.5 mg of morphine intrathecally before induction of anesthesia for cardiopulmonary bypass surgery were reviewed. Anesthesia was maintained with isoflurane and no patient received intravenous narcotics intraoperatively. Postoperative analgesic requirements were low, with 7 of 10 patients requiring no supplemental analgesic during the first 12 hours. Early extubation (within 8 hours of arrival in the intensive care unit) was possible in 8 patients; two patients remained intubated for reasons unrelated to the anesthetic technique. No patient required naloxone, reintubation, or treatment for respiratory depression. Combined intrathecal sufentanil and morphine provided conditions that allowed successful early extubation in 8 of 10 of these selected cardiac surgery patients.
 
The use and the hemodynamic effects of propofol and midazolam were studied during titrated continuous infusions to deep sedation (sedation level 5: asleep, sluggish response to light glabellar tap or loud auditory stimulus) following coronary artery surgery. The drugs were compared in 30 ventilated patients in an open randomized study. The duration of infusion was approximately 570 minutes in both groups. After a loading dose of propofol (1 mg/kg) or midazolam (0.07 mg/kg), the infusion rates were 2.71 +/- 1.13 mg/kg/h and 0.092 +/- 0.028 mg/kg/h, respectively. An analgesic infusion of sufentanil was also given in both groups. In the midazolam group, to maintain the predetermined level of sedation, more frequent additional bolus doses (4.7 +/- 1.8; P < 0.001) and infusion rate adjustments (5.3 +/- 1.6; P < 0.001) were required than for similar sedation in the propofol group (2.3 +/- 1.0 bolus doses and 3.3 +/- 1.2 adjustments). The time from stopping sedation to patient responsiveness was 11 +/- 8 minutes in the propofol group and 72 +/- 70 minutes in the midazolam group (P < 0.001), and the time from stopping sedation to extubation was 250 +/- 135 minutes and 391 +/- 128 minutes (P < 0.014), respectively. Following the loading dose of propofol, there was a fall in blood pressure (BP) (mean from 80 +/- 11 mmHg to 67.5 +/- 10 mmHg; P < 0.05). After approximately 15 minutes, BP started to rise but remained below pretreatment level throughout sedation.(ABSTRACT TRUNCATED AT 250 WORDS)
 
To evaluate the effects of milrinone on middle cerebral artery blood flow velocity (Vmca) and pulsatility index (PI) during normocapnia and hyperventilation in adults after cardiopulmonary bypass (CPB). A prospective study. University-affiliated hospital and Veterans Affairs Medical Center. Twenty-five adults with left ventricular ejection fraction >40% undergoing coronary artery bypass graft surgery. After separation from CPB, using transcranial Doppler ultrasonography, peak and mean Vmca and PI were recorded before and after the administration of 50 microg/kg of milrinone under normocapnia and with hyperventilation. Heart rate, arterial blood pressure, central venous pressure, and cardiac output were documented after each study period. Compared with baseline, milrinone increased peak Vmca by 20%, increased mean Vmca by 19%, and decreased PI by 16% (p < 0.001). Before the administration of milrinone, hyperventilation decreased peak Vmca by 20%, decreased mean Vmca by 26%, and increased PI by 24% (p < 0.01). After milrinone administration, hyperventilation also decreased peak Vmca by 22%, decreased mean Vmca by 21%, and increased PI by 19% (p < 0.01). Milrinone increased cardiac index and decreased mean arterial pressure and systemic vascular resistance (p < 0.05); however, heart rate and central venous pressure remained unchanged. The administration of milrinone increases cerebral blood flow after CPB most likely as a result of cerebral vasodilation. The response to hyperventilation seems to be partially preserved.
 
The aim of this study was to summarize the immediate outcome after aortic valve replacement (AVR) with or without coronary artery bypass grafting (CABG). Systematic review and meta-analysis. University hospitals. Participants were 683,286 patients who underwent AVR with or without CABG. Patients undergoing other major cardiac procedures were excluded from this analysis. AVR with or without CABG. Operative mortality after AVR with or without concomitant CABG was 4.3%, stroke 2.1%, pacemaker implantation 5.9%, and dialysis 2.2%. After isolated AVR, operative mortality was 3.3%, stroke 1.7%, pacemaker implantation 3.3%, and dialysis 1.6%. Mortality was increased among very elderly (<60 years: 3.3%, 60-69 years: 2.7%, 70-79 years: 3.8%,≥80 years: 6.1%, p<0.001). Prevalence of minimally invasive AVR (mini-AVR) was associated with significantly lower operative mortality (p = 0.039, 46 studies). Mini-AVR only tended toward lower mortality when included in meta-regression analysis as a dichotomous variable (mini-AVR 4,367 patients: 2.3%, 95% CI 1.8-2.9% v full sternotomy 11,076 patients: 3.5%, 95% CI 28-4.1%, p = 0.088). Operative mortality after AVR plus CABG was 5.5% (versus isolated AVR: p<0.001), stroke 3.0%, pacemaker implantation 3.9%, and dialysis 5.6%. Mortality was high in all age strata, particularly among very elderly (mean age<70 years: 4.8%, mean age 70-79 years: 4.7%; mean age≥80 years: 8.4%, p = 0.002). Isolated AVR is associated with low mortality and morbidity. Coronary artery disease requiring concomitant CABG increases the operative mortality. Patients requiring AVR and CABG should be the main target of less-invasive treatment strategies.
 
To investigate the anti-inflammatory and hemodynamic effects of 17beta-estradiol in men undergoing elective coronary artery bypass graft surgery (CABG). Prospective, randomized, controlled. Operating room and intensive care unit in a university hospital. Twenty-one men undergoing primary, elective CABG surgery. 17beta-estradiol, 2mg, was given orally twice in 14 hours before the operation. Leukocyte counts, plasma myeloperoxidase, tumor necrosis factor-alpha, interleukin (IL)-6, IL-8, and IL-10 were measured perioperatively. Leukocyte counts were lower in the 17beta-estradiol group than in controls at 6 hours (11.4 +/- 2.0 hours v 15.5 +/- 4.7 hours x 10(9)/L) and 20 hours (11.6 +/- 1.9 hours v 13.6 +/- 2.5 hours x 10(9)/L) after reperfusion (p = 0.03). The release of myeloperoxidase was lower in the 17beta-estradiol group than in controls (5 minutes; 634.4 +/- 213.1 microg/mL v 773.1 +/- 209.3 microg/mL; 4 hours, 305.0 +/- 108.0 microg/mL v 441.3 +/- 191.6 microg/mL; p = 0.02). Systemic vascular resistance index was lower just after cardiopulmonary bypass, and cardiac index was higher postoperatively in the 17beta-estradiol group as compared with controls. Pretreatment with 17beta-estradiol can limit leukocyte activation in men after CABG surgery.
 
To undertake neuropsychologic testing within 18 hours of cardiac surgery after fast-track anesthesia. Prospective study. University hospital, single center. Fifty patients undergoing first-time elective coronary artery surgery. A neuropsychologic test battery was administered preoperatively and 18 hours and 5 days after surgery. Seven patients were withdrawn, and 9 patients did not attempt the postoperative tests (on both occasions) because of medical complications. Thirty patients completed > or =4 tests at both postoperative occasions. Of these, 9 patients (30%) showed a deficit in > or =2 tests at 18 hours postoperatively, and 3 (10%) showed a deficit at 5 days postoperatively. In the absence of medical complications and despite the difficulties, early postoperative neuropsychologic testing is possible after fast-track anesthesia. Such testing has the potential to more clearly define the course of cognitive decline after cardiac surgery.
 
To study complications from spinal fluid drainage in open thoracic/thoracoabdominal and thoracic endovascular aortic aneurysm repairs to define risks of spinal fluid drainage. Retrospective, prospectively maintained, institutionally approved database. Single institution university center. 724 patients treated from 1987 to 2013 INTERVENTIONS: The authors drained spinal fluid to a pressure≤6 mmHg during thoracic aortic occlusion/reperfusion in open and≤8 mmHg after stent deployment in endovascular procedures. Low pressure was maintained until leg strength was documented. If bloody fluid appeared, drainage was stopped. Head computed tomography (CT) and, if indicated, spine CT and magnetic resonance imaging (MRI) were performed for bloody spinal fluid or neurologic deficit. Spinal fluid drainage was studied for bloody fluid, CT/MRI-identified intracranial and spinal bleeding, neurologic deficit, and death. Seventy-three patients (10.1%) had bloody fluid; 38 (5.2%) had intracranial blood on CT. One patient had spinal epidural hematoma. Higher volume of fluid drained and higher central venous pressure during proximal clamping were associated with intracranial blood. Most patients with intracranial blood were asymptomatic. Six patients had neurologic deficits: of the 6, 3 died (0.4%), 1 (0.1%) had permanent hemiparesis, and 2 recovered. Three of the six deficits were delayed, associated with heparin anticoagulation. 10% of patients had bloody spinal fluid; half of these had intracranial bleeding, which was almost always asymptomatic. In these patients, immediately stopping drainage and correcting coagulopathy may decrease the risk of serious complications. Neurologic deficit from spinal fluid drainage is uncommon (0.8%), but has high morbidity and mortality. Copyright © 2014 Elsevier Inc. All rights reserved.
 
Objective: The bibliometrics of the anesthesiology literature has shifted substantially during the past 3 decades. The present authors analyzed the Journal of Cardiothoracic and Vascular Anesthesia (JCVA) at selected time intervals from 1990 to 2011 to quantify temporal variations in geographic publication patterns. The authors also determined whether previously described reductions in North American research productivity were accompanied by similar decreases in the number of other forms of publication in JCVA. Design: An observational study. Setting: Internet analysis. Interventions: None. Measurements and main results: The number of research articles, case reports and conferences, review articles, and letters in each issue of the journal were quantified in each of 4 time intervals consisting of consecutive 4-year periods (1990-1993, 1996-1999, 2002-2005, and 2008-2011). Forty-three countries published a total of 2,587 articles (ie, 1,141 research articles, 735 case reports, 175 review articles, and 536 letters) during the 4 time periods examined. Progressive decreases in the percentage of research articles, case reports, and letters, but not review articles, from North America were observed over time. Significant increases in the percentage of research articles and letters contributed by European authors in 2008 to 2011 were observed compared with 1990 to 1993. The percentage of all publications from the Middle East and Australasia increased significantly, whereas South America and Africa were relatively minor contributors to JCVA throughout the study period. Conclusions: The present bibliometric analysis indicates that JCVA has changed from a journal that primarily published work from countries in North America and Europe to one in which the Middle East and Australasia now make a substantial number of contributions. These results suggest that JCVA has evolved into a truly international journal since its inception in 1987.
 
Top-cited authors
Bruce Spiess
  • University of Florida
John Augoustides
  • Hospital of the University of Pennsylvania
Stefan De Hert
  • Ghent University
Fabio Guarracino
  • Azienda Ospedaliero-Universitaria Pisana
Yatin Mehta
  • Medanta The Medicity