Publications by authors named "Ivo Brandes"

24 Publications

  • Page 1 of 1

Transesophageal echocardiography for perioperative management in thoracic surgery.

Curr Opin Anaesthesiol 2021 Feb;34(1):7-12

Department of Anesthesiology, University of Colorado, School of Medicine, Aurora, Colorado, USA.

Purpose Of Review: Perioperative transesophageal echocardiography (TEE) is most often employed during cardiac surgery. This review will summarize some of the recent findings relevant to TEE utilization during thoracic surgical procedures.

Recent Findings: Hemodynamic monitoring is a key component of goal-directed fluid therapy, which is also becoming more common for management of thoracic surgical procedures. Although usually not required for the anesthetic management of common thoracic surgeries, TEE is frequently used during lung transplantation and pulmonary thromboendarterectomy. Few clinical studies support current practice patterns, and most recommendations are based on expert opinion.

Summary: Currently, routine use of TEE in thoracic surgery is often limited to specific high-risk patients and/or procedures. As in other perioperative settings, TEE may be utilized to elucidate the reasons for acute hemodynamic instability without apparent cause. Contraindications to TEE apply and have to be taken into consideration before performing a TEE on a thoracic surgical patient.
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http://dx.doi.org/10.1097/ACO.0000000000000947DOI Listing
February 2021

Accuracy of zero-heat-flux thermometry and bladder temperature measurement in critically ill patients.

Sci Rep 2020 12 10;10(1):21746. Epub 2020 Dec 10.

Department of Anesthesiology, University Medical Center Göttingen, Robert-Koch Strasse 40, 37099, Göttingen, Germany.

Core temperature (T) monitoring is essential in intensive care medicine. Bladder temperature is the standard of care in many institutions, but not possible in all patients. We therefore compared core temperature measured with a zero-heat flux thermometer (T) and with a bladder catheter (T) against blood temperature (T) as a gold standard in 50 critically ill patients in a prospective, observational study. Every 30 min T, T and T were documented simultaneously. Bland-Altman statistics were used for interpretation. 7018 pairs of measurements for the comparison of T with T and 7265 pairs of measurements for the comparison of T with T could be used. T represented T more accurate than T. In the Bland Altman analyses the bias was smaller (0.05 °C vs. - 0.12 °C) and limits of agreement were narrower (0.64 °C to - 0.54 °C vs. 0.51 °C to - 0.76 °C), but not in clinically meaningful amounts. In conclusion the results for zero-heat-flux and bladder temperatures were virtually identical within about a tenth of a degree, although T tended to underestimate T. Therefore, either is suitable for clinical use.German Clinical Trials Register, DRKS00015482, Registered on 20th September 2018, http://apps.who.int/trialsearch/Trial2.aspx?TrialID=DRKS00015482 .
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http://dx.doi.org/10.1038/s41598-020-78753-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730188PMC
December 2020

Diagnostic Value of Cholinesterase Activity for the Development of Postoperative Delirium after Cardiac Surgery.

Thorac Cardiovasc Surg 2020 Nov 20. Epub 2020 Nov 20.

Department of Thoracic and Cardiovascular Surgery, University Hospital, Georg-August-University, Göttingen, Germany.

Background:  Depression of cholinesterase (CHE) activity has been reported to lead to an amplified neuroinflammatory response, which clinically manifests as postoperative delirium (PD). This observational study investigates the association between CHE activity and the development of PD following elective cardiac surgery.

Methods:  Patients with preexisting neurologic deficits or carotid artery disease as well as patients undergoing reoperations or procedures under circulatory arrest have been excluded from this study. The Mini-Mental State Examination, the Confusion Assessment Method for the Intensive Care Unit, and the Intensive Care Delirium Screening Checklist were performed at regular intervals. CHE activity was estimated pre- and postoperatively until postoperative day (POD) 5 and at discharge.

Results:  A total of 107 patients were included. PD was diagnosed in 34 (31.8%) patients, who have been compared with those without PD. Time on ventilator, length of ICU, and hospital stay were longer in patients with PD ( = 0.001,  < 0.001, and  = 0.004, respectively). MMSE scores were lower in patients with PD ( < 0.001;  = 0.015). CHE activity on POD 1 to 4 as well as at discharge were lower in the delirium group ( = 0.041;  = 0.029;  = 0.015;  = 0.035;  = 0.028, respectively). A perioperative drop of CHE activity of more than 50% and a postoperative CHE activity below 4,800 U/L (on POD 0) were independently associated with an increased risk of development of PD ( = 0.038;  = 0.008, respectively).

Conclusion:  In addition to the established functional tests, routine estimation of CHE activity may serve as an additional diagnostic tool allowing for the timely diagnosis and treatment of PD in cardiac surgery patients.
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http://dx.doi.org/10.1055/s-0040-1716897DOI Listing
November 2020

Influence of oral premedication and prewarming on core temperature of cardiac surgical patients: a prospective, randomized, controlled trial.

BMC Anesthesiol 2019 04 12;19(1):55. Epub 2019 Apr 12.

Department of Anaesthesiology, University Medical Center Göttingen, Robert-Koch-Str. 40, 37075, Göttingen, Germany.

Background: Perioperative hypothermia is still very common and associated with numerous adverse effects. The effects of benzodiazepines, administered as premedication, on thermoregulation have been studied with conflicting results. We investigated the hypotheses that premedication with flunitrazepam would lower the preoperative core temperature and that prewarming could attenuate this effect.

Methods: After approval by the local research ethics committee 50 adult cardiac surgical patients were included in this prospective, randomized, controlled, single-centre study with two parallel groups in a university hospital setting. Core temperature was measured using a continuous, non-invasive zero-heat flux thermometer from 30 min before administration of the oral premedication until beginning of surgery. An equal number of patients was randomly allocated via a computer-generated list assigning them to either prewarming or control group using the sealed envelope method for blinding. The intervention itself could not be blinded. In the prewarming group patients received active prewarming using an underbody forced-air warming blanket. The data were analysed using Student's t-test, Mann-Whitney U-test and Fisher's exact test.

Results: Of the randomized 25 patients per group 24 patients per group could be analysed. Initial core temperature was 36.7 ± 0.2 °C and dropped significantly after oral premedication to 36.5 ± 0.3 °C when the patients were leaving the ward and to 36.4 ± 0.3 °C before induction of anaesthesia. The patients of the prewarming group had a significantly higher core temperature at the beginning of surgery (35.8 ± 0.4 °C vs. 35.5 ± 0.5 °C, p = 0.027), although core temperature at induction of anaesthesia was comparable. Despite prewarming, core temperature did not reach baseline level prior to premedication (36.7 ± 0.2 °C).

Conclusions: Oral premedication with benzodiazepines on the ward lowered core temperature significantly at arrival in the operating room. This drop in core temperature cannot be offset by a short period of active prewarming.

Trial Registration: This trial was prospectively registered with the German registry of clinical trials under the trial number DRKS00005790 on 20th February 2014.
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http://dx.doi.org/10.1186/s12871-019-0725-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466686PMC
April 2019

Flow-controlled ventilation during ear, nose and throat surgery: A prospective observational study.

Eur J Anaesthesiol 2019 05;36(5):327-334

From the Department of Anaesthesiology and Critical Care, Medical Centre - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg (JS, FG, JW, SW, SS), Department of Anaesthesiology, Emergency and Intensive Care Medicine, University Medical Centre Göttingen, Göttingen, Germany (IB), University of Greenwich, London, UK (TB), and Department of Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Münster, Germany (AZ, DE).

Background: Flow-controlled ventilation (FCV) is a new mechanical ventilation mode that maintains constant flow during inspiration and expiration with standard tidal volumes via cuffed narrow-bore endotracheal tubes. Originating in manually operated 'expiratory ventilation assistance', FCV extends this technique by automatic control of airway flow, monitoring of intratracheal pressure and control of peak inspiratory pressure and end-expiratory pressure. FCV has not yet been described in a clinical study.

Objective: The aim of this study was to provide an initial assessment of FCV in mechanically ventilated patients undergoing ear, nose and throat surgery and evaluate its potential for future use.

Design: An observational study.

Setting: Two German academic medical centres from 24 November 2017 to 09 January 2018.

Patients: Consecutive patients (≥ 18 years) scheduled for elective ear, nose and throat surgery. Exclusion criteria were planned laser surgery, intended fibreoptic awake intubation, emergency procedures, increased risk of aspiration, American Society of Anesthesiologists (ASA) physical status more than III and chronic obstructive pulmonary disease classified as GOLD stage more than II.

Intervention: Peri-operative use of FCV provided by a new type of ventilator (Evone) via a narrow-bore endotracheal tube (Tritube).

Main Outcome Measures: Minute volume, respiratory rate, intratidal tracheal pressure amplitude (Δp) and end-tidal CO2 (PetCO2) were recorded every 5 min. All adverse events were noted. Data are presented as median [IQR].

Results: Sixteen patients provided 15 evaluable data sets. A minute volume of 5.0 [4.4 to 6.4] l min and a respiratory rate of 9 [8 to 11] min generated a PetCO2 of 4.9 [4.8 to 5.0] kPa. Δp was 10 [9 to 12] cmH2O. Five adverse events were recorded: a tube obstruction due to airway secretions and four tube dislocations (two attributed to coughing, two not study-related).

Conclusion: FCV achieves adequate PetCO2 levels with minute volume and Δp in the normal range. Tritube's high flow resistance may increase the likelihood of tube dislocations if the patient coughs. Although further evaluation is necessary, FCV provides a new option for short-term mechanical ventilation. The successful operation of FCV with narrow-bore tubes contributes to the armamentarium for airway management.

Trial Registration: DRKS00013312.
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http://dx.doi.org/10.1097/EJA.0000000000000967DOI Listing
May 2019

Genome-wide association study of myocardial infarction, atrial fibrillation, acute stroke, acute kidney injury and delirium after cardiac surgery - a sub-analysis of the RIPHeart-Study.

BMC Cardiovasc Disord 2019 01 24;19(1):26. Epub 2019 Jan 24.

Department of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt, Germany.

Background: The aim of our study was the identification of genetic variants associated with postoperative complications after cardiac surgery.

Methods: We conducted a prospective, double-blind, multicenter, randomized trial (RIPHeart). We performed a genome-wide association study (GWAS) in 1170 patients of both genders (871 males, 299 females) from the RIPHeart-Study cohort. Patients undergoing non-emergent cardiac surgery were included. Primary endpoint comprises a binary composite complication rate covering atrial fibrillation, delirium, non-fatal myocardial infarction, acute renal failure and/or any new stroke until hospital discharge with a maximum of fourteen days after surgery.

Results: A total of 547,644 genotyped markers were available for analysis. Following quality control and adjustment for clinical covariate, one SNP reached genome-wide significance (PHLPP2, rs78064607, p = 3.77 × 10) and 139 (adjusted for all other outcomes) SNPs showed promising association with p < 1 × 10 from the GWAS.

Conclusions: We identified several potential loci, in particular PHLPP2, BBS9, RyR2, DUSP4 and HSPA8, associated with new-onset of atrial fibrillation, delirium, myocardial infarction, acute kidney injury and stroke after cardiac surgery.

Trial Registration: The study was registered with ClinicalTrials.gov NCT01067703, prospectively registered on 11 Feb 2010.
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http://dx.doi.org/10.1186/s12872-019-1002-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6345037PMC
January 2019

Association between perioperative hypothermia and patient outcomes after thoracic surgery: A single center retrospective analysis.

Medicine (Baltimore) 2018 Apr;97(17):e0528

Department of Anaesthesiology.

Hypothermia due to anaesthetic-induced impairment of thermoregulatory control and exposure to a cool environment is common in surgical patients. Peripheral vasodilation due to neuroaxial blockade may aggravate hypothermia. There is few data on perioperative hypothermia in patients undergoing thoracic surgery under combined general and regional anesthesia. We reviewed all thoracic surgical patients between 2006 and 2011 to determine the incidence and extent of hypothermia with or without an epidural anesthesia and evaluated its effect.Around 339 patients underwent lung resection procedures with intraoperative forced-air warming: 197 with general and epidural anesthesia (GA + EPI), 199 with general anesthesia alone (GA). Statistical analyses were performed to determine the association between hypothermia (T < 36°C) and transfusion requirements, length of stay (LOS) in the intensive care unit (ICU), hospital LOS, and in hospital mortality.The overall incidence of hypothermia was 64.3%. Multivariate regression analysis revealed three significant risk factors for the development of hypothermia: long induction time (P = .011), small body surface area (P = .003), and application of more fluid intraoperatively (P < .001). Factors determining the extent of hypothermia were: receiving an open thoracotomy (P = .009), placement and use of an epidural catheter (P = .002), and a lower body mass index (BMI) (P < .001). Additional epidural anesthesia reduced core temperature by 0.26°C (95% CI -0.414 to -0.095°C, P < .05). There was no difference in transfusion requirements, ICU LOS or mortality between both groups. Hospital LOS was longer in patients with hypothermia.More than half of all thoracic patients suffered from hypothermia. A long induction time, small body surface area, and large intraoperative fluid application were independent risk factors for the development of perioperative hypothermia. Additional epidural anesthesia to general anesthesia did not increase the incidence of hypothermia but decreased body core temperature to an-albeit not clinically significant-degree. Patients scheduled for thoracic surgery will probably benefit from an additional period of prewarming prior to induction to reduce the high incidence of perioperative hypothermia.
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http://dx.doi.org/10.1097/MD.0000000000010528DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5944492PMC
April 2018

RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study: Myocardial Dysfunction, Postoperative Neurocognitive Dysfunction, and 1 Year Follow-Up.

J Am Heart Assoc 2018 03 26;7(7). Epub 2018 Mar 26.

Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.

Background: Remote ischemic preconditioning (RIPC) has been suggested to protect against certain forms of organ injury after cardiac surgery. Previously, we reported the main results of RIPHeart (Remote Ischemic Preconditioning for Heart Surgery) Study, a multicenter trial randomizing 1403 cardiac surgery patients receiving either RIPC or sham-RIPC.

Methods And Results: In this follow-up paper, we present 1-year follow-up of the composite primary end point and its individual components (all-cause mortality, myocardial infarction, stroke and acute renal failure), in a sub-group of patients, intraoperative myocardial dysfunction assessed by transesophageal echocardiography and the incidence of postoperative neurocognitive dysfunction 5 to 7 days and 3 months after surgery. RIPC neither showed any beneficial effect on the 1-year composite primary end point (RIPC versus sham-RIPC 16.4% versus 16.9%) and its individual components (all-cause mortality [3.4% versus 2.5%], myocardial infarction [7.0% versus 9.4%], stroke [2.2% versus 3.1%], acute renal failure [7.0% versus 5.7%]) nor improved intraoperative myocardial dysfunction or incidence of postoperative neurocognitive dysfunction 5 to 7 days (67 [47.5%] versus 71 [53.8%] patients) and 3 months after surgery (17 [27.9%] versus 18 [27.7%] patients), respectively.

Conclusions: Similar to our main study, RIPC had no effect on intraoperative myocardial dysfunction, neurocognitive function and long-term outcome in cardiac surgery patients undergoing propofol anesthesia.

Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01067703.
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http://dx.doi.org/10.1161/JAHA.117.008077DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5907591PMC
March 2018

Unexpectedly high incidence of hypothermia before induction of anesthesia in elective surgical patients.

J Clin Anesth 2016 Nov 16;34:282-9. Epub 2016 May 16.

Department of Anesthesiology, University of Goettingen, Robert-Koch-Str 40, 37075 Goettingen, Germany.

Study Objective: Perioperative hypothermia is a frequently observed phenomenon of general anesthesia and is associated with adverse patient outcome. Recently, a significant influence of core temperature before induction of anesthesia has been reported. However, there are still little existing data on core temperature before induction of anesthesia and no data regarding potential risk factors for developing preoperative hypothermia. The purpose of this investigation was to estimate the incidence of hypothermia before anesthesia and to determine if certain factors predict its incidence.

Design/setting/patients: Data from 7 prospective studies investigating core temperature previously initiated at our department were analyzed. Patients undergoing a variety of elective surgical procedures were included.

Interventions/measurements: Core temperature was measured before induction of anesthesia with an oral (314 patients), infrared tympanic (143 patients), or tympanic contact thermometer (36 patients). Available potential predictors included American Society of Anesthesiologists status, sex, age, weight, height, body mass index, adipose ratio, and lean body weight. Association with preoperative hypothermia was assessed separately for each predictor using logistic regression. Independent predictors were identified using multivariable logistic regression.

Main Results: A total of 493 patients were included in the study. Hypothermia was found in 105 patients (21.3%; 95% confidence interval, 17.8%-25.2%). The median core temperature was 36.3°C (25th-75th percentiles, 36.0°C-36.7°C). Two independent factors for preoperative hypothermia were identified: male sex and age (>52years).

Conclusions: As a consequence of the high incidence of hypothermia before anesthesia, measuring core temperature should be mandatory 60 to 120minutes before induction to identify and provide adequate treatment to hypothermic patients.
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http://dx.doi.org/10.1016/j.jclinane.2016.03.065DOI Listing
November 2016

Comparison of Conductive and Convective Warming in Patients Undergoing Video-Assisted Thoracic Surgery: A Prospective Randomized Clinical Trial.

Thorac Cardiovasc Surg 2017 Aug 13;65(5):362-366. Epub 2016 May 13.

Department of Anesthesiology, University Medical Center, Georg-August University,Goettingen, Germany.

 Perioperative hypothermia is frequent during thoracic surgery. After approval by the local ethics committee and written informed consent from patients, we examined the efficiency of prewarming and intraoperative warming with a convective warming system and conductive warming system to prevent perioperative hypothermia during video-assisted thoracic surgery (VATS).  We randomized 60 patients with indication for VATS in two groups (convective warming with an underbody blanket vs. conductive warming with an underbody mattress and additional warming of the legs). All patients were prewarmed before induction of anesthesia with the corresponding system. Core temperature was measured sublingual and in the nasopharynx.  Both groups were not significantly different in regard to clinical parameter, prewarming, and initial core temperature. The patients in conduction group had lower intraoperative core temperatures and a higher incidence of intraoperative (73.9 vs. 24%) and postoperative hypothermia (56.5 vs. 8%) compared with convective warming.  Pre- and intraoperative convective warming with an underbody blanket prevents perioperative hypothermia during VATS better than conductive warming. The inferior prevention in conductive warming group may be caused by reduced body contact to the warming mattresses in lateral position.
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http://dx.doi.org/10.1055/s-0036-1583766DOI Listing
August 2017

Perioperative Blood Glucose Levels <150 mg/dL are Associated With Improved 5-Year Survival in Patients Undergoing On-Pump Cardiac Surgery: A Prospective, Observational Cohort Study.

Medicine (Baltimore) 2015 Nov;94(45):e2035

From the Department of Anesthesiology, University Medical Center, Georg August University, Goettingen, Germany (AM, IB, IFB, MB, JH); Department of Cardiothoracic Transplantation and Mechanical Support, Royal Brompton and Harefield Hospital, Harefield, London, UK (AFP); Department of Medical Informatics, University of Amsterdam, Amsterdam, The Netherlands (AAH); and Department of Medical Statistics, University Medical Center, Georg August University, Goettingen, Germany (TB).

Hyperglycemia is common during and after Coronary Artery Bypass Graft Surgery (CABGS) and has been shown to be associated with poor clinical outcomes. In this study, we hypothesized that a moderate perioperative mean blood glucose level of <150 mg/dL improves long-term survival in cardiac surgery patients. We conducted a prospective, observational cohort study in the heart center of the University Medical Center of Goettingen, Germany. Patients undergoing on-pump cardiac surgery were enrolled in this investigation. After evaluating perioperative blood glucose levels, patients were classified into 2 groups based on mean glucose levels: Glucose ≥150 mg/dL and Glucose <150 mg/dL. Patients were followed up for 5 years, and mortality within this period was recorded as the primary outcome parameter. Secondary outcome parameters included the length of ICU stay, the use of inotropic agents, the length of hospital stay, and the in-hospital mortality. A total of 455 consecutive patients who underwent cardiac surgery with cardiopulmonary bypass were enrolled in this investigation. A Kaplan-Meier survival analysis of the 5-year mortality risk revealed a higher mortality risk among patients with glucose levels ≥150 mg/dL (P = 0.0043, log-rank test). After adjustment for confounders in a multivariate Cox regression model, the association between glucose ≥150 mg/dL and 5-year mortality remained significant (hazard ratio, 2.10; 95% CI, 1.30-3.39; P = 0.0023). This association was corroborated by propensity score matching, in which Kaplan-Meier survival analysis demonstrated significant improvement in the 5-year survival of patients with glucose levels <150 mg/dL (P = 0.0339). Similarly, in-hospital mortality was significantly higher in patients with glucose ≥150 mg/dL compared with patients with glucose <150 mg/dL. Moreover, patients in the Glucose ≥150 mg/dL group required significantly higher doses of the inotropic agent Dobutamine (mg/d) compared with patients in the Glucose <150 mg/dL group (20.6 ± 62.3 and 10.5 ± 40.7, respectively; P = 0.0104). Moreover, patients in the Glucose ≥150 mg/dL group showed a significantly longer hospital stay compared with patients in the Glucose <150 mg/dL group (28 ± 23 and 24 ± 19, respectively; P = 0.0297). We conclude that perioperative blood glucose levels <150 mg/dL are associated with improved 5-year survival in patients undergoing cardiac surgery. More studies are warranted to explain this effect.
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http://dx.doi.org/10.1097/MD.0000000000002035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4912304PMC
November 2015

A Multicenter Trial of Remote Ischemic Preconditioning for Heart Surgery.

N Engl J Med 2015 Oct 5;373(15):1397-407. Epub 2015 Oct 5.

From the Department of Anesthesiology, Intensive Care Medicine, and Pain Therapy, University Hospital Frankfurt, Frankfurt (P.M., U.S., C.R., K.Z.), the Departments of Anesthesiology and Intensive Care Medicine (P.M., B.B., M.G.) and Cardiovascular Surgery (J.C.), University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Clinical Trial Center (O.B.), the Department of Internal Medicine/Cardiology, University of Leipzig Heart Center (G.F.), and Institute for Medical Informatics, Statistics, and Epidemiology (D.H.), University of Leipzig, Leipzig, the Department of Anesthesiology, University Hospital Aachen, Aachen (C.S., M.C., G.S.), the Department of Cardiovascular Surgery, University of Giessen, Giessen (A.B., B.N.), Clinic of Anesthesiology and Intensive Care Medicine, University Hospital Rostock, Rostock (J.R., F.K.), the Department of Anesthesiology, Medical Center of Johannes Gutenberg University, Mainz (R.L.-F., M.F.), the Department of Anesthesiology and Intensive Care Medicine, University Hospital Göttingen, Göttingen (I.F.B., M.B.), the Department of Anesthesiology and Intensive Care Medicine and Center for Sepsis Control and Care, Jena University Hospital, Jena (S.N.S., A.K.), the Department of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn (M.W., G.B.), the Department of Anesthesiology and Intensive Care Medicine, University Hospital Düsseldorf, Düsseldorf (T.M.-T., P.K.), the Department of Anesthesiology and Intensive Care Medicine, University of Lübeck, Lübeck (M.H., J.S.), the Department of Anesthesiology and Intensive Care Medicine, Charité-Universitätsmedizin Berlin, Campus Charité Mitte, Berlin (M.S., S.T.), the Department of Anesthesiology, University Hospital Würzburg, Würzburg (T. Smul, E.W.), and the Department of Anesthesiology, University Hospital Magdeburg, Magdeburg (T. Schilling) - all in Germany.

Background: Remote ischemic preconditioning (RIPC) is reported to reduce biomarkers of ischemic and reperfusion injury in patients undergoing cardiac surgery, but uncertainty about clinical outcomes remains.

Methods: We conducted a prospective, double-blind, multicenter, randomized, controlled trial involving adults who were scheduled for elective cardiac surgery requiring cardiopulmonary bypass under total anesthesia with intravenous propofol. The trial compared upper-limb RIPC with a sham intervention. The primary end point was a composite of death, myocardial infarction, stroke, or acute renal failure up to the time of hospital discharge. Secondary end points included the occurrence of any individual component of the primary end point by day 90.

Results: A total of 1403 patients underwent randomization. The full analysis set comprised 1385 patients (692 in the RIPC group and 693 in the sham-RIPC group). There was no significant between-group difference in the rate of the composite primary end point (99 patients [14.3%] in the RIPC group and 101 [14.6%] in the sham-RIPC group, P=0.89) or of any of the individual components: death (9 patients [1.3%] and 4 [0.6%], respectively; P=0.21), myocardial infarction (47 [6.8%] and 63 [9.1%], P=0.12), stroke (14 [2.0%] and 15 [2.2%], P=0.79), and acute renal failure (42 [6.1%] and 35 [5.1%], P=0.45). The results were similar in the per-protocol analysis. No treatment effect was found in any subgroup analysis. No significant differences between the RIPC group and the sham-RIPC group were seen in the level of troponin release, the duration of mechanical ventilation, the length of stay in the intensive care unit or the hospital, new onset of atrial fibrillation, and the incidence of postoperative delirium. No RIPC-related adverse events were observed.

Conclusions: Upper-limb RIPC performed while patients were under propofol-induced anesthesia did not show a relevant benefit among patients undergoing elective cardiac surgery. (Funded by the German Research Foundation; RIPHeart ClinicalTrials.gov number, NCT01067703.).
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http://dx.doi.org/10.1056/NEJMoa1413579DOI Listing
October 2015

Evaluation of a novel noninvasive continuous core temperature measurement system with a zero heat flux sensor using a manikin of the human body.

Biomed Tech (Berl) 2015 Feb;60(1):1-9

Reliable continuous perioperative core temperature measurement is of major importance. The pulmonary artery catheter is currently the gold standard for measuring core temperature but is invasive and expensive. Using a manikin, we evaluated the new, noninvasive SpotOn™ temperature monitoring system (SOT). With a sensor placed on the lateral forehead, SOT uses zero heat flux technology to noninvasively measure core temperature; and because the forehead is devoid of thermoregulatory arteriovenous shunts, a piece of bone cement served as a model of the frontal bone in this study. Bias, limits of agreements, long-term measurement stability, and the lowest measurable temperature of the device were investigated. Bias and limits of agreement of the temperature data of two SOTs and of the thermistor placed on the manikin's surface were calculated. Measurements obtained from SOTs were similar to thermistor values. The bias and limits of agreement lay within a predefined clinically acceptable range. Repeat measurements differed only slightly, and stayed stable for hours. Because of its temperature range, the SOT cannot be used to monitor temperatures below 28°C. In conclusion, the new SOT could provide a reliable, less invasive and cheaper alternative for measuring perioperative core temperature in routine clinical practice. Further clinical trials are needed to evaluate these results.
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http://dx.doi.org/10.1515/bmt-2014-0063DOI Listing
February 2015

Remote ischaemic preconditioning for heart surgery. The study design for a multi-center randomized double-blinded controlled clinical trial--the RIPHeart-Study.

Eur Heart J 2012 Jun;33(12):1423-6

Clinic of Anaesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Theodor-Stern-Kai 7, Frankfurt am Main, Germany.

Aims: Transient ischaemia of non-vital tissue has been shown to enhance the tolerance of remote organs to cope with a subsequent prolonged ischaemic event in a number of clinical conditions, a phenomenon known as remote ischaemic preconditioning (RIPC). However, there remains uncertainty about the efficacy of RIPC in patients undergoing cardiac surgery. The purpose of this report is to describe the design and methods used in the "Remote Ischaemic Preconditioning for Heart Surgery (RIPHeart)-Study".

Methods: We are conducting a prospective, randomized, double-blind, multicentre, controlled trial including 2070 adult cardiac surgical patients. All types of surgery in which cardiopulmonary bypass is used will be included. Patients will be randomized either to the RIPC group receiving four 5 min cycles of transient upper limb ischaemia/reperfusion or to the control group receiving four cycles of blood pressure cuff inflation/deflation at a dummy arm. The primary endpoint is a composite outcome (all-cause mortality, non-fatal myocardial infarction, any new stroke, and/or acute renal failure) until hospital discharge.

Conclusion: The RIPHeart-Study is a multicentre trial to determine whether RIPC may improve clinical outcome in cardiac surgical patients.
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June 2012

Intensified thermal management for patients undergoing transcatheter aortic valve implantation (TAVI).

J Cardiothorac Surg 2011 Sep 25;6:117. Epub 2011 Sep 25.

Department of Anesthesiology, Emergency and Intensive Care Medicine, University of Göttingen, Robert-Koch-Str, 40, 37075 Göttingen, Germany.

Background: Transcatheter aortic valve implantation via the transapical approach (TAVI-TA) without cardiopulmonary bypass (CPB) is a minimally invasive alternative to open-heart valve replacement. Despite minimal exposure and extensive draping perioperative hypothermia still remains a problem.

Methods: In this observational study, we compared the effects of two methods of thermal management on the perioperative course of core temperature. The methods were standard thermal management (STM) with a circulating hot water blanket under the patient, forced-air warming with a lower body blanket and warmed infused fluids, and an intensified thermal management (ITM) with additional prewarming using forced-air in the pre-operative holding area on the awake patient.

Results: Nineteen patients received STM and 20 were treated with ITM. On ICU admission, ITM-patients had a higher core temperature (36.4±0.7°C vs. 35.5±0.9°C, p=0.001), required less time to achieve normothermia (median (IQR) in min: 0 (0-15) vs. 150 (0-300), p=0.003) and a shorter period of ventilatory support (median (IQR) in min: 0 (0-0) vs. 246 (0-451), p=0.001).

Conclusion: ITM during TAVI-TA reduces the incidence of hypothermia and allows for faster recovery with less need of ventilatory support.
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http://dx.doi.org/10.1186/1749-8090-6-117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203847PMC
September 2011

REM sleep-like episodes of motoneuronal depression and respiratory rate increase are triggered by pontine carbachol microinjections in in situ perfused rat brainstem preparation.

Exp Physiol 2011 May 18;96(5):548-55. Epub 2011 Feb 18.

Department of Anaesthesiology, Emergency and Intensive Care Medicine, University Medicine Gottingen, Georg August University, Gottingen, Germany.

Hypoglossal nerve activity (HNA) controls the position and movements of the tongue. In persons with compromised upper airway anatomy, sleep-related hypotonia of the tongue and other pharyngeal muscles causes increased upper airway resistance, or total upper airway obstructions, thus disrupting both sleep and breathing. Hypoglossal nerve activity reaches its nadir, and obstructive episodes are longest and most severe, during rapid eye movement stage of sleep (REMS). Microinjections of a cholinergic agonist, carbachol, into the pons have been used in vivo to investigate the mechanisms of respiratory control during REMS. Here, we recorded inspiratory-modulated phrenic nerve activity and HNA and microinjected carbachol (25-50 nl, 10 mm) into the pons in an in situ perfused working heart-brainstem rat preparation (WHBP), an ex vivo model previously validated for studies of the chemical and reflex control of breathing. Carbachol microinjections were made into 40 sites in 33 juvenile rat preparations and, at 24 sites, they triggered depression of HNA with increased respiratory rate and little change of phrenic nerve activity, a pattern akin to that during natural REMS in vivo. The REMS-like episodes started 151 ± 73 s (SD) following microinjections, lasted 20.3 ± 4.5 min, were elicited most effectively from the dorsal part of the rostral nucleus pontis oralis, and were prevented by perfusion of the preparation with atropine. The WHBP offers a novel model with which to investigate cellular and neurochemical mechanisms of REMS-related upper airway hypotonia in situ without anaesthesia and with full control over the cellular environment.
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http://dx.doi.org/10.1113/expphysiol.2010.056242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4500117PMC
May 2011

Feasibility of implantable cardioverter defibrillator treatment in five patients with familial Friedreich's ataxia--a case series.

Artif Organs 2010 Nov;34(11):1061-5

Department of Thoracic Cardiovascular Surgery, University of Göttingen, Germany.

Friedreich's ataxia (FRA) is an autosomal recessive disease of the central nervous system that is associated with familial cardiomyopathy. Cardiac involvement is seen in more than 90% of the patients and is the most common cause of death in these patients. We present a case series and discuss the indications for implantable cardioverter defibrillator (ICD) implantation in FRA with review of the literature. Five pediatric patients who suffer from FRA (four female and one male, mean age 17.4 years) underwent ICD implantation between 2007 and 2008 in the University Hospital of Goettingen. The diagnosis of FRA was established by standard clinical criteria and proven in each case by genotyping at the frataxin locus. The time from diagnosis to ICD implantation was 10.4±1.73 years (range 8-15 years). All patients received transvenous lead systems. There were no intraoperative and postoperative complications. At the latest follow-up, the neuromuscular symptoms exhibited no further progress and no ICD activations were noticed. Only minor repolarization changes were seen on electrocardiogram. All patients had normal echocardiographic findings and no angina has been reported. Coronary angiographies were normal. It is evident that many FRA patients develop ventricular dysfunction. In the absence of a definitive surgical cure an ICD is generally indicated in young patients with hemodynamically significant sustained ventricular tachyarrhythmias for prevention of sudden cardiac death. Our experience implies the safe use of ICD in children with FRA.
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http://dx.doi.org/10.1111/j.1525-1594.2010.01140.xDOI Listing
November 2010

Anesthetic effects on synaptic transmission and gain control in respiratory control.

Respir Physiol Neurobiol 2008 Dec;164(1-2):151-9

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI, USA.

All volatile and most intravenous general anesthetics currently in clinical use cause respiratory depression at concentrations suitable for surgery. While various in vitro studies have identified potential molecular targets, their contributions to respiratory depression are poorly understood. At surgical concentrations, anesthetics principally affect ligand-gated, rather than voltage-gated ion channels. Here we focus on anesthetic-induced effects on synaptic transmission in brainstem respiratory neurons. The spontaneous discharge patterns of canine respiratory bulbospinal premotor neurons in vivo depend principally on NMDA and non-NMDA receptor-mediated excitation, while GABAA receptors mediate gain modulation and silent-phase inhibition. Studies examining the effects of volatile anesthetics on synaptic neurotransmission to these neurons suggest a primary role for postsynaptic enhancement of GABAA receptor function, partly offset by a reduction in presynaptic inhibition and a presynaptic reduction in glutamatergic excitation. In studies involving canine inspiratory hypoglossal motoneurons in vivo, which are already strongly depressed by low concentrations (< 0.5 MAC) of volatile anesthetics, the role of acid-sensitive, two-pore domain K+ (TASK) channels was found to be minimal at these subanesthetic concentrations. Potentiation of GABAA receptor-mediated inhibition was suggested. These studies on canine respiratory neurons provide valuable insights into mechanisms of anesthetic depression within a respiratory control subsystem; future studies will be required to determine anesthetic effects on sources of respiratory drive, rhythm, and their control.
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http://dx.doi.org/10.1016/j.resp.2008.05.007DOI Listing
December 2008

Major components of endogenous neurotransmission underlying the discharge activity of hypoglossal motoneurons in vivo.

Adv Exp Med Biol 2008 ;605:279-84

Medical College of Wisconsin, Anesthesiology Department, USA.

Multibarrel micropipettes were used to simultaneously record unit activity and apply antagonists on individual inspiratory hypoglossal motoneurons (IHMNs) to determine the endogenous activation levels of NMDA, non-NMDA, GABA(A) and serotonin receptors responsible for the IHMN spontaneous discharge patterns in decerebrate dogs. IHMN activity is highly dependent on glutamatergic phasic and tonic drives, which are differentially mediated by the receptor subtypes. Endogenous serotonin significantly amplifies IHMN activity, while GABAergic gain modulation acts to attenuate activity. Thus, alterations in the neurotransmission of any of these systems could markedly alter neuronal output to target muscles.
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http://dx.doi.org/10.1007/978-0-387-73693-8_49DOI Listing
January 2008

Isoflurane depresses the response of inspiratory hypoglossal motoneurons to serotonin in vivo.

Anesthesiology 2007 Apr;106(4):736-45

Department of Anesthesiology, Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin, USA.

Background: Endogenous serotonin (5-HT) provides important excitatory drive to inspiratory hypoglossal motoneurons (IHMNs). In vitro studies show that activation of postsynaptic 5-HT receptors decreases a leak K+ channel conductance and depolarizes hypoglossal motoneurons (HMNs). In contrast, volatile anesthetics increase this leak K+ channel conductance, which causes neuronal membrane hyperpolarization and depresses HMN excitability. Clinical studies show upper airway obstruction, indicating HMN depression, even at subanesthetic concentrations. The authors hypothesized that if anesthetic activation of leak K+ channels caused neuronal depression in vivo, this effect could be antagonized with serotonin. In this case, the neuronal response to picoejected serotonin would be greater during isoflurane than with no isoflurane.

Methods: Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The authors studied the effect of approximately 0.3 minimum alveolar concentration (MAC) isoflurane on the spontaneous discharge frequency patterns of single IHMNs and on the neuronal response to picoejection of 5-HT.

Results: Normalized data (mean +/- SD, n = 19) confirmed that 0.3 +/- 0.1 MAC isoflurane markedly reduced the spontaneous peak discharge frequency by 48 +/- 19% (P < 0.001) and depressed the slope of the spontaneous discharge patterns. The increase in neuronal frequency in response to 5-HT was reduced by 34 +/- 22% by isoflurane (P < 0.001).

Conclusion: Subanesthetic concentrations of isoflurane strongly depressed canine IHMNs in vivo. The neuronal response to 5-HT was also depressed by isoflurane, suggesting that anesthetic activation of leak K+ channels, which is expected to result in a larger 5-HT response, was not a dominant mechanism in this depression.
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http://dx.doi.org/10.1097/01.anes.0000264750.93769.99DOI Listing
April 2007

Retrograde labeling reveals extensive distribution of genioglossal motoneurons possessing 5-HT2A receptors throughout the hypoglossal nucleus of adult dogs.

Brain Res 2007 Feb 26;1132(1):110-9. Epub 2006 Dec 26.

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.

Inspiratory hypoglossal motoneurons (IHMNs) innervate the muscles of the tongue and play an important role in maintaining upper airway patency. However, this may be reduced during sleep and by sedatives, potent analgesics, and volatile anesthetics. The genioglossal (GG) muscle is the main protruder and depressor muscle of the tongue and contributes to upper airway patency during inspiration. In vitro data suggest that serotonin (5-hydroxytryptamine, 5-HT), via the 5-HT(2A) receptor (5-HT(2A)R) subtype, plays a key role in controlling the excitability of IHMNs. The distribution of GG motoneurons (GGMNs) within the hypoglossal (XII) nucleus has not been studied in the adult dog. Further, it is uncertain whether the 5-HT(2A)R is located on GGMNs in the adult dog. We therefore used the cholera toxin B (CTB) subunit as a retrograde tracer to map the location of GGMNs in combination with immunofluorescent labeling to determine the presence and colocalization of 5-HT(2A)R within the XII nucleus in adult mongrel dogs. Injection of CTB into the GG muscle resulted in retrogradely labeled cells in a compact column throughout the XII nucleus, extending from 0.75 mm caudal to 3.45 mm rostral to the obex. Fluorescence immunohistochemistry revealed extensive 5-HT(2A)R labeling on CTB-labeled GGMNs. Identification of the 5-HT(2A)R on GGMNs in the XII nucleus of the adult dog supports in vitro data and suggests a physiological role for this receptor subtype in controlling the excitability of GGMNs, which contribute to the maintenance of upper airway patency.
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http://dx.doi.org/10.1016/j.brainres.2006.10.099DOI Listing
February 2007

Use of BIS monitor in a child with congenital insensitivity to pain with anhidrosis.

Paediatr Anaesth 2006 Apr;16(4):466-70

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53201, USA.

We describe a case of a 14-year-old boy with congenital insensitivity to pain and anhidrosis (CIPA) who underwent tarsal tunnel release for tarsal tunnel syndrome. Because of abnormal pain perception, the patient's response to normally painful surgical stimuli is severely impaired and not adequately reflected in a corresponding rise in blood pressure or heart rate. This lack of autonomic feedback to pain stimuli may make it more difficult to assess whether anesthetic depth is adequate to prevent intraoperative awareness and thus to safely conduct anesthesia, especially if muscle paralysis is required for surgical indications. We describe for the first time the use of processed EEG monitoring with a BIS A-2000 monitor to gauge anesthetic depth in a patient with CIPA. Initial forehead bispectral index (BIS) values prior to induction were normal (98) and then ranged between 23 and 79 during the whole surgical procedure. Propofol and lidocaine were used for induction and deep extubation; isoflurane was used as the sole anesthetic for maintenance with concentrations ranging from 0.21% to 0.92% to maintain a target BIS of 40-60. Volatile anesthetic requirements remained low throughout the procedure and no narcotics were necessary during surgery. The BIS monitor served as an adequate tool to help avoid excessive use of volatile anesthetic while assuring a processed EEG consistent with unconsciousness and amnesia. After the patient had recovered and was oriented to place and time in the recovery room, he was asked whether he remembered anything about the surgery and the presence of a breathing tube in his mouth. He denied any recall of such events.
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http://dx.doi.org/10.1111/j.1460-9592.2005.01745.xDOI Listing
April 2006

Serotonergic modulation of inspiratory hypoglossal motoneurons in decerebrate dogs.

J Neurophysiol 2006 Jun 22;95(6):3449-59. Epub 2006 Feb 22.

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.

Inspiratory hypoglossal motoneurons (IHMNs) maintain upper airway patency. However, this may be compromised during sleep and by sedatives, potent analgesics, and volatile anesthetics by either depression of excitatory or enhancement of inhibitory inputs. In vitro data suggest that serotonin (5-HT), through the 5-HT2A receptor subtype, plays a key role in controlling the excitability of IHMNs. We hypothesized that in vivo 5-HT modulates IHMNs activity through the 5-HT2A receptor subtype. To test this hypothesis, we used multibarrel micropipettes for extracellular single neuron recording and pressure picoejection of 5-HT or ketanserin, a selective 5-HT2A receptor subtype antagonist, onto single IHMNs in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs. Drug-induced changes in neuronal discharge frequency (F(n)) and neuronal discharge pattern were analyzed using cycle-triggered histograms. 5-HT increased the control peak F(n) to 256% and the time-averaged F(n) to 340%. 5-HT increased the gain of the discharge pattern by 61% and the offset by 34 Hz. Ketanserin reduced the control peak F(n) by 68%, the time-averaged F(n) by 80%, and the gain by 63%. These results confirm our hypothesis that in vivo 5-HT is a potent modulator of IHMN activity through the 5-HT2A receptor subtype. Application of exogenous 5-HT shows that this mechanism is not saturated during hypercapnic hyperoxia. The two different mechanisms, gain modulation and offset change, indicate that 5-HT affects the excitability as well as the excitation of IHMNs in vivo.
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http://dx.doi.org/10.1152/jn.00823.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2582383PMC
June 2006

Sevoflurane enhances gamma-aminobutyric acid type A receptor function and overall inhibition of inspiratory premotor neurons in a decerebrate dog model.

Anesthesiology 2005 Jul;103(1):57-64

Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, USA.

Background: Inspiratory premotor neurons in the caudal ventral medulla relay excitatory drive to phrenic and inspiratory intercostal motoneurons in the spinal cord. These neurons are subject to tonic gamma-aminobutyric acid type A (GABAA)ergic inhibition. In a previous study, 1 minimum alveolar concentration (MAC) sevoflurane depressed overall glutamatergic excitatory drive and enhanced overall GABAAergic inhibitory drive to the neurons. This study investigated in further detail the effects of sevoflurane on GABAAergic inhibition by examining postsynaptic GABAA receptor activity in these neurons.

Methods: Studies were performed in decerebrate, vagotomized, paralyzed, and mechanically ventilated dogs during hypercapnic hyperoxia. The effect of 1 MAC sevoflurane on extracellularly recorded neuronal activity was measured during localized picoejection of the GABAA receptor antagonist bicuculline and the GABAA agonist muscimol. Complete blockade of GABAAergic inhibition by bicuculline allowed estimation of the prevailing overall inhibition of the neuron. The neuronal response to muscimol was used to assess the anesthetic effect on the postsynaptic GABAA receptor function.

Results: One MAC sevoflurane depressed the spontaneous activity of 21 inspiratory premotor neurons by (mean +/- SD) 32.6 +/- 20.5% (P < 0.001). Overall excitatory drive was depressed 17.9 +/- 19.8% (P < 0.01). Overall GABAAergic inhibition was enhanced by 18.5 +/- 18.2% (P < 0.001), and the postsynaptic GABAA receptor function was increased by 184.4 +/- 121.8% (n = 20; P < 0.001).

Conclusion: One MAC sevoflurane greatly enhanced GABAA receptor function on inspiratory premotor neurons and increased overall synaptic inhibition but to a smaller extent, indicating that the presynaptic inhibitory input was also reduced. Therefore, the anesthetic depression of spontaneous inspiratory premotor neuronal activity by 1 MAC sevoflurane in vivo is due to a combined effect on the two major ionotropic synaptic neurotransmitter systems with a decrease in overall glutamatergic excitation and a strong enhancement of postsynaptic GABAA receptor function.
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http://dx.doi.org/10.1097/00000542-200507000-00012DOI Listing
July 2005