Wolfgang Konertz

Bispectral index-guided sedation with dexmedetomidine in intensive care : a prospective, randomized, double blind, placebo-controlled phase II study

ObjectiveTo compare dexmedetomidine vs. placebo with respect to the amount of additional propofol and morphine used for bispectral index-guided sedation and analgesia in mechanically ventilated, intensive care patients after surgery. DesignProspective, randomized, double blind, placebo-controlled, phase II clinical trial. SettingGeneral surgical and cardiac surgical intensive care units. PatientsThirty patients scheduled for major surgery requiring mechanical ventilation for a minimum of 6 hrs were included in the study. InterventionsPatients were assigned randomly to receive either dexmedetomidine (loading infusion, 6.0 &mgr;g·kg−1·hr−1 for 10 mins; maintenance infusion, 0.1–0.7 &mgr;g·kg−1·hr−1) or placebo after intensive care unit admission. Measurements and Main ResultsSedation was guided by using the electroencephalographic parameter bispectral index, a new noninvasive method to estimate the level of sedation. We aimed at maintaining bispectral index ranges between 60 and 70 during mechanical ventilation before starting weaning, 65 and 95 during weaning, and 85 to 95 postextubation. Additional sedative and analgesic medication was given (propofol and morphine) as clinically indicated and within the previously mentioned bispectral index ranges. Patients receiving dexmedetomidine required significantly less propofol during mechanical ventilation (0.87 ± 0.21 vs. 1.52 ± 0.30 mg·kg−1·hr−1;p < .01) and weaning (0.17 ± 0.06 vs. 0.62 ± 0.21 mg·kg−1·hr−1;p < .001) to maintain the target bispectral index range. During study drug administration, morphine requirements for dexmedetomidine-treated patients were reduced by 58% (p = .05). Hemodynamic stability during weaning and after extubation was better maintained in patients receiving dexmedetomidine. ConclusionsDexmedetomidine reduced propofol requirements and improved hemodynamic stability during bispectral index-guided intensive care unit sedation.

Ross operation with a tissue-engineered heart valve

BACKGROUND The Ross procedure has gained increasing acceptance due to excellent hemodynamic results by replacing the diseased aortic valve with the viable autologous pulmonary valve. Consequently, the right ventricular outflow tract (RVOT) has to be reconstructed. In this report a viable heart valve was created from decellularized cryopreserved pulmonary allograft that was seeded with viable autologous vascular endothelial cells (AVEC). METHODS A 43-year-old patient suffering from aortic valve stenosis underwent a Ross operation on May 20, 2000, using a tissue engineered (TE) pulmonary allograft to reconstruct the RVOT. Four weeks before the operation a piece of forearm vein was harvested to separate, culture, and characterize AVEC. Follow-up was completed at discharge, 3, 6, and 12 months postoperatively by clinical evaluation, transthoracic echocardiography (TTE), and magnetic resonance imaging (MRI). Additionally, at 1-year follow-up a multislice computed tomographic scan was performed. RESULTS After four weeks of culturing 8.34 x 10(6) AVEC were available to seed a 27-mm decellularized pulmonary allograft. Trypan blue staining confirmed 96.0% viability. Reendothelialization rate after seeding was 9.0 x 10(5) cells/cm2. TTE and MRI revealed excellent hemodynamic function of the TE heart valve and the neoaortic valve as well. Multislice computed tomography revealed no evidence of valvular calcification. CONCLUSIONS After 1 year of follow-up the patient is in excellent condition without limitation and exhibits normal aortic and pulmonary valve function.

Hyperprocalcitonemia in patients with noninfectious SIRS and pulmonary dysfunction associated with cardiopulmonary bypass

Background The incidence of noninfectious systemic inflammatory response syndrome (SIRS) associated with coronary artery bypass surgery and the potential role of several inflammatory parameters as early markers of pulmonary dysfunction induced by cardiopulmonary bypass (CPB) were investigated. Methods Forty patients undergoing elective coronary artery bypass surgery were studied prospectively. Perioperative lung function was monitored using the lung injury score introduced by Murray and colleagues, by measuring venous admixture (Qs/Qt), and, in some cases, by measuring extravascular lung water. Serum concentrations of the inflammatory parameters (procalcitonin, interleukin‐6, sL‐selectin, leukocyte elastase, neopterin, leukocyte counts, and C‐reactive protein) were determined sequentially. The American College of Chest Physicians‐Society of Critical Care Medicine classification system was used to diagnose SIRS. Results According to the entry criteria, SIRS developed in 17 (42%) patients after operation. Nine patients of this group showed signs of acute pulmonary impairment, whereas patients without SIRS had no lung injury. In all patients with acute lung injury, distinct increases in procalcitonin concentrations ranging from 5.1 to 14.3 ng/ml were measured. In patients with SIRS but without acute lung injury and in patients without SIRS, none or only negligible increases in serum concentrations of procalcitonin were seen. Compared with procalcitonin, other inflammatory parameters investigated were less sensitive and less specific to indicate pulmonary dysfunction secondary to CPB. Conclusions Procalcitonin seems to be an appropriate parameter indicating the early development of severe noninfectious SIRS and for predicting pulmonary dysfunction secondary to CPB.

Global surgical experience with the Acorn cardiac support device.

OBJECTIVE Surgical intervention is an option for treating the remodeled and dilated left ventricles of patients with heart failure. Providing end-diastolic support with an innovative mesh-like cardiac support device reduces mechanical stress, improves function, and reverses cardiac remodeling in animal models without safety issues. The objective of this study was to review the global clinical safety and feasibility experience of this device. METHODS The Acorn CorCap cardiac support device (Acorn Cardiovascular, Inc, St Paul, Minn) has been implanted worldwide in more than 130 patients with dilated cardiomyopathy with or without concomitant cardiac surgery. The device is positioned around the ventricles and given a custom fit. A series of 48 patients were implanted with the device in initial safety and feasibility studies, of whom 33 also received concomitant cardiac surgery. RESULTS At implantation, 11 patients were in New York Heart Association class II, 33 were in class III, and 4 were in class IV. The average CorCap implantation time was 27 minutes. The mean intraoperative reduction in left ventricular end-diastolic dimension was 4.6% +/- 1%. There were no device-related intraoperative complications. Eight early and 9 late deaths occurred during follow-up extending to 24 months. Actuarial survival was 73% at 12 months and 68% at 24 months. There were no device-related adverse events or evidence of constrictive disease, and coronary artery flow reserve was maintained. Ventricular chamber dimensions decreased, whereas ejection fraction and New York Heart Association class were improved in patients overall and in those patients implanted with the CorCap device without concomitant operations. CONCLUSIONS The CorCap device appears safe for patients with dilated cardiomyopathy. Randomized clinical trials are underway in Europe, Australia, and North America.

Clinical Experience With the MEDOS HIA-VAD System in Infants and Children: A Preliminary Report

BACKGROUND The need of pediatric cardiac assist is growing because of the complexity of the congenital conditions operated on and the increasing number of pediatric transplantations. We evaluated the newly developed pediatric MEDOS HIA-VAD ventricular assist device. METHODS The pneumatic paracorporeal ventricular assist device has three left ventricular sizes (10-, 25-, and 60-mL maximum stroke volume) and three right ventricular sizes (9, 22.5, and 54 mL) and can be operated effectively with up to 180 cycles/min. We used this device in 6 consecutive pediatric patients. Intention of treatment was to bridge to transplantation in 3 patients and to aid in recovery from a cardiac operation in 3. Age ranged from 5 days to 8 years. RESULTS Two children died during assist, 2 were weaned from the system and discharged home, and 2 had successful transplantation. During assist, laboratory variables indicative of impaired renal, hepatic, or pulmonary function normalized or showed a trend toward normalization. Both deaths were related to infection. CONCLUSIONS With the new MEDOS HIA-VAD ventricular assist device system, pediatric mechanical cardiac assist can be performed successfully. It requires timely implantation, careful monitoring, and adequate size-matched devices.

Validity and reliability of the DDS for severity of delirium in the ICU.

Introduction: Until now, there has been no gold standard for monitoring delirium in intensive care unit (ICU) patients. In this prospective cohort study, a new score, the Delirium Detection Score (DDS), for severity of delirium in the ICU was evaluated.Methods: After ethical approval and written informed consent, intensive care doctors and nurses assessed 1073 consecutive patients in surgical ICUs using the DDS together with the Ramsay Sedation Scale (RSS). The DDS is composed of eight criteria (orientation, hallucination, agitation, anxiety, seizures, tremor, paroxysmal sweating, and altered sleepwake rhythm). Additionally, intensive care doctors had to document the Sedation-Agitation Scale (SAS) combined with a defined clinical assessment. For interrater reliability, pair of evaluators assessed patients in a blinded fashion at the same time.Results: RSS1 (9%) was associated with a significantly (p<0.001) higher DDS than RSS levels 2–6. The DDS increased with the severity of delirium (p< 0.001). The receiver operating characteristics (ROC) for the differentiation between no delirium (SAS<4) and symptoms of delirium at all (SAS 5–7) showed an area under the curve (AUC) of 0.802 (95% confidential interval (CI): 0.719–0.898; p<0.001) and 69% sensitivity and 75% specificity was determined. For reliability, a Cronbach’s α of 0.667 was calculated. The paired comparisons revealed an intraclass correlation between 0.642 and 0.758.Conclusion: The DDS demonstrated good validity with excellent sensitivity and specificity for delirium. The severity of delirium can be more accurately estimated by the DDS. By its composition of several items, the DDS might help to start a symptom-guided therapy immediately.

Preoperative oral carbohydrate administration to ASA III-IV patients undergoing elective cardiac surgery

In this study we investigated the effects of preoperative oral carbohydrate administration on postoperative insulin resistance (PIR), gastric fluid volume, preoperative discomfort, and variables of organ dysfunction in ASA physical status III-IV patients undergoing elective cardiac surgery, including those with noninsulin-dependent Type-2 diabetes mellitus. Before surgery, 188 patients were randomized to receive a clear 12.5% carbohydrate drink (CHO), flavored water (placebo), or to fast overnight (control). CHO and placebo were treated in double-blind format and received 800 mL of the corresponding beverage in the evening and 400 mL 2 h before surgery. Patients were monitored from induction of general anesthesia until 24 h postoperatively. Exogenous insulin requirements to control blood glucose levels ≤10.0 mmol/L were used as a marker for PIR. Gastric fluid volume was measured by passive gastric reflux and preoperative discomfort using visual analog scales. Postoperative clinical and surgical data were recorded. Blood glucose levels and insulin requirements did not differ between groups. Patients receiving CHO and placebo were less thirsty compared with controls (P < 0.01 and P = 0.06, respectively). Ingested liquids did not cause increased gastric fluid volume or other adverse events. The CHO group required less intraoperative inotropic support after initiation of cardiopulmonary bypass weaning (P < 0.05). In conclusion, preoperative CHO administration before cardiac surgery does not affect PIR. Clear fluids reduce thirst and may be recommended as a safe procedure in ASA III-IV patients. Further research is indicated to investigate possible cardioprotective effects of preoperative CHO intake.

Ten Years of Clinical Results With a Tissue-Engineered Pulmonary Valve

BACKGROUND This study was performed to collect prospective safety and effectiveness data from a tissue-engineered heart valve implanted for reconstruction of the right ventricular outflow tract during the Ross operation. METHODS From May 2000 until June 2002, 11 consecutive patients, mean age 39.6 ± 10.3 years, received a tissue-engineered heart valve (additive and logistic European System for Cardiac Operative Risk Evaluation, respectively, 3.3 ± 1.3 and 2.8% ± 1.4%). Two to four weeks prior to the Ross operation a piece of forearm vein or saphenous vein was harvested to isolate, characterize, and expand endothelial cells. A cryopreserved pulmonary allograft was decellularized, coated, and seeded with autologous vascular endothelial cells, using a specially developed bioreactor. Cell seeding density was 1.1 × 10(5) ± 0.5 × 10(5) cells/cm(2) with a viability of 93.2% ± 2.1%. RESULTS All patients survived surgery. Postoperatively no fever of unknown origin was evident. Currently all patients are in New York Heart Association class I. Evaluation of the tissue-engineered heart valve by transthoracic echocardiography showed a mean pressure gradient of 5.4 ± 2.0 mm Hg at 10 years. Multislice computed tomography showed no calcification up to 10 years. CONCLUSIONS Tissue-engineered heart valves showed excellent hemodynamic performance and may prevent degeneration during long-term follow-up.

Three-year survival after four major post-cardiac operative complications.

Objective:After cardiac surgery, major morbidities known to be primary contributors to perioperative mortality are cardiac failure, respiratory failure, renal failure, and the need for mediastinal exploration. The first aim of this study was to ascertain long-term survival in cardiac surgery patients with and without the occurrence of major morbidities to investigate if long-term survival was comparable. The second aim of this study was to evaluate the prevalences and risk factors related to the four major morbidities in this patient population. Design:Retrospective observational outcome study. Setting:Cardiothoracic intensive care unit at a university hospital. Patients:We included 2,683 of 3,253 consecutive cardiac surgery patients cared for in a uniform fashion. Methods and Main Results:Perioperative mortality was significantly increased by the occurrence of major morbidity. In-hospital mortality was 0.7% in the absence of major morbidity compared with 72% when all major morbidities occurred. Three-year mortality for the entire study population was 15%, whereas the 3-yr long-term survival was significantly less for patients with morbidities compared with those without. Various independent perioperative risk factors were found for perioperative major morbidity and mortality. Conclusions:Successful acute treatment and measures to identify and reduce the risk of major morbidities are necessary to improve outcome. In addition, long-term follow-up and management of morbidities are necessary to possibly improve long-term survival.

Pulse contour analysis after normothermic cardiopulmonary bypass in cardiac surgery patients

IntroductionMonitoring of the cardiac output by continuous arterial pulse contour (COPiCCOpulse) analysis is a clinically validated procedure proved to be an alternative to the pulmonary artery catheter thermodilution cardiac output (COPACtherm) in cardiac surgical patients. There is ongoing debate, however, of whether the COPiCCOpulse is accurate after profound hemodynamic changes. The aim of this study was therefore to compare the COPiCCOpulse after cardiopulmonary bypass (CPB) with a simultaneous measurement of the COPACtherm.MethodsAfter ethical approval and written informed consent, data of 45 patients were analyzed during this prospective study. During coronary artery bypass graft surgery, the aortic transpulmonary thermodilution cardiac output (COPiCCOtherm) and the COPACtherm were determined in all patients. Prior to surgery, the COPiCCOpulse was calibrated by triple transpulmonary thermodilution measurement of the COPiCCOtherm. After termination of CPB, the COPiCCOpulse was documented. Both COPACtherm and COPiCCOtherm were also simultaneously determined and documented.ResultsRegression analysis between COPACtherm and COPiCCOtherm prior to CPB showed a correlation coefficient of 0.95 (P < 0.001), and after CPB showed a correlation coefficient of 0.82 (P < 0.001). Bland-Altman analysis showed a mean bias and limits of agreement of 0.0 l/minute and -1.4 to +1.4 l/minute prior to CPB and of 0.3 l/minute and -1.9 to +2.5 l/minute after CPB, respectively. Regression analysis of COPiCCOpulse versus COPiCCOtherm and of COPiCCOpulse versus COPACtherm after CPB showed a correlation coefficient of 0.67 (P < 0.001) and 0.63 (P < 0.001), respectively. Bland-Altman analysis showed a mean bias and limits of agreement of -1.1 l/minute and -1.9 to +4.1 l/minute versus -1.4 l/minute and -4.8 to +2.0 l/minute, respectively.ConclusionWe observed an excellent correlation of COPiCCOtherm and COPACtherm measurement prior to CPB. Pulse contour analysis did not yield reliable results with acceptable accuracy and limits of agreement under difficult conditions after weaning from CPB in cardiac surgical patients. The pulse contour analysis thus should be re-calibrated as soon as possible, to prevent false therapeutic consequences.