The Influence of Audiovisual Distraction on Pain Reduction During Transcatheter Aortic Valve Implantation Under Monitored Anesthesia Care: A Prospective Randomized Trial.

OBJECTIVES: To investigate the effect of an audiovisual distraction system on the dose of remifentanil for perioperative sedation during transcatheter aortic valve implantation under monitored anesthesia care. DESIGN: Single-center prospective randomized nonblinded study. SETTING: Tertiary referral academic hospital. PARTICIPANTS: Ninety patients who underwent transfemoral transcatheter aortic valve implantation between July 2019 and July 2021. INTERVENTIONS: Patients were randomized to use either a novel audiovisual distraction system during the intervention (n = 45) or standard care without an audiovisual distraction system (n = 45). MEASUREMENTS AND MAIN RESULTS: Standardized questionnaires were given to each patient at admission and before and after the intervention to assess their levels of anxiety. Primary endpoints were the average and peak infusion rates of remifentanil. All patients were considered for the final analysis according to an intention-to-treat design. No relevant differences in pre- and postinterventional anxiety status were observed between the groups. Similarly, there were no significant differences in reported pain scores (p = 0.364). The average infusion rate (p = 0.028) and peak infusion rate (p = 0.025) of remifentanil were lower in the group with an audiovisual distraction system. CONCLUSIONS: Audiovisual distraction is a useful adjunct to reduce the dose of remifentanil under monitored anesthesia care during transcatheter aortic valve implantation. Larger studies are needed to evaluate potential positive effects on patient satisfaction, incidence of delirium, and possible economic benefits.

Systematic Assessment of Shock Severity in Postoperative Cardiac Surgery Patients.

BACKGROUND: The Society for Cardiovascular Angiography and Interventions (SCAI) shock classification has been shown to provide robust mortality risk stratification in a variety of cardiovascular patients. OBJECTIVES: This study sought to evaluate the SCAI shock classification in postoperative cardiac surgery intensive care unit (CSICU) patients. METHODS: This study retrospectively analyzed 26,792 postoperative CSICU admissions at a heart center between 2012 and 2022. Patients were classified into SCAI shock stages A to E using electronic health record data. Moreover, the impact of late deterioration (LD) as an additional risk modifier was investigated. RESULTS: The proportions of patients in SCAI shock stages A to E were 24.4%, 18.8%, 8.4%, 35.5%, and 12.9%, and crude hospital mortality rates were 0.4%, 0.6%, 3.3%, 4.9%, and 30.2%, respectively. Similarly, the prevalence of postoperative complications and organ dysfunction increased across SCAI shock stages. After multivariable adjustment, each higher SCAI shock stage was associated with increased hospital mortality (adjusted OR: 1.26-16.59) compared with SCAI shock stage A, as was LD (adjusted OR: 8.2). The SCAI shock classification demonstrated a strong diagnostic performance for hospital mortality (area under the receiver operating characteristic: 0.84), which noticeably increased when LD was incorporated into the model (area under the receiver operating characteristic: 0.90). CONCLUSIONS: The SCAI shock classification effectively risk-stratifies postoperative CSICU patients for mortality, postoperative complications, and organ dysfunction. Its application could, therefore, be extended to the field of cardiac surgery as a triage tool in postoperative care and as a selection criterion in research.

Minimally Invasive Extirpation of Benign Atrial Cardiac Tumors: Clinical Follow-Up and Survival.

OBJECTIVE: Evidence determining the optimal treatment for cardiac tumors is rare. We report our midterm clinical outcome and patient characteristics of our series undergoing atrial tumor removal through a right lateral minithoracotomy (RLMT). METHODS: From 2015 to 2021, 51 patients underwent RLMT for atrial tumor extirpation. Patients receiving concomitant atrioventricular valvular, cryoablation, and/or patent foramen ovale closure surgery were included. Follow-up was performed using standardized questionnaires (mean: 1,041 ± 666 days). Follow-up involved any tumor recurrence, clinical symptoms, and any recurrent arterial embolization. Survival analysis was successfully achieved in all patients. RESULTS: Successful surgical resection was achieved in all patients. Mean cardiopulmonary bypass and cross-clamping times were 75 ± 36 and 41 ± 22 min, respectively. The most common tumor location was the left atrium (n = 42, 82.4%). Mean ventilation time was 12.74 ± 17.23 h, intensive care unit stay ranged from 1 to 1.9 days (median: 1 day). Nineteen patients (37.3%) received concomitant surgery. Histopathological analysis showed 38 myxoma (74.5%), 9 papillary fibroelastoma (17.6%), and 4 thrombus (7.8%). Thirty-day mortality was observed in 1 case (2%). One patient (2%) suffered a stroke postoperatively. No patient had a relapse of cardiac tumor. Three patients (9.7%) showed arterial embolization during follow-up. Thirteen follow-up patients (25.5%) were in New York Heart Association class ≤II. Overall survival was 90.2% at 2 years. CONCLUSIONS: A minimally invasive approach for benign atrial tumor resection is effective, safe, and reproducible. Of the atrial tumors, 74.5% were myxoma and 82% were located in the left atrium. A low 30-day mortality rate with no manifestation of recurrent intracardiac tumor was observed.

Improving Survival in Cardiogenic Shock-A Propensity Score-Matched Analysis of the Impact of an Institutional Allocation Protocol to Short-Term Mechanical Circulatory Support.

Temporary mechanical circulatory support (tMCS) is a life-saving treatment option for patients in cardiogenic shock (CS), but many aspects such as patient selection, initiation threshold and optimal modality selection remain unclear. This study describes a standard operating procedure (SOP) for tMCS allocation for CS patients and presents outcome data before and after implementation. Data from 421 patients treated for CS with tMCS between 2018 and 2021 were analyzed. In 2019, we implemented a new SOP for allocating CS patients to tMCS modalities. The association between the time of SOP implementation and the 30-day and 1-year survival as well as hospital discharge was evaluated. Of the 421 patients included, 189 were treated before (pre-SOP group) and 232 after implementation of the new SOP (SOP group). Causes of CS included acute myocardial infarction (n = 80, 19.0%), acute-on-chronic heart failure in patients with dilated or chronic ischemic heart failure (n = 139, 33.0%), valvular cardiomyopathy (n = 14, 3.3%) and myocarditis (n = 5, 1.2%); 102 patients suffered from postcardiotomy CS (24.2%). The SOP group was further divided into an SOP-adherent (SOP-A) and a non-SOP-adherent group (SOP-NA). The hospital discharge rate was higher in the SOP group (41.7% vs. 29.7%), and treating patients according to the SOP was associated with an improved 30-day survival (56.9% vs. 38.9%, OR 2.21, 95% CI 1.01-4.80, p = 0.044). Patient allocation according to the presented SOP significantly improved 30-day survival.

Single-Center Experience With a Self-Expandable Venous Cannula During Minimally Invasive Cardiac Surgery.

OBJECTIVE: Venous drainage is often problematic in minimally invasive cardiac surgery (MICS). Here, we describe our experience with a self-expandable stent cannula designed to optimize venous drainage. METHODS: The smart canula® was used in 58 consecutive patients undergoing MICS for mitral valve disease (n = 40), left atrial myxoma (n = 3), left ventricular outflow tract obstruction (n = 1), and aortic valve replacement via a right anterior minithoracotomy (n = 14) procedures. The venous cannula was placed under transesophageal echocardiography guidance to reach the superior vena cava. Vacuum-assisted venous drainage (between -20 and -35 mm Hg) was used to reach a target flow index of 2.2 L/min/m² at a core temperature of 34 °C using a goal-directed perfusion strategy aimed at a minimum DO2 of 272 mL/min/m2. Cardiopulmonary bypass (CPB) parameters were recorded, and hemolysis-related parameters were analyzed on postoperative days 1 to 7. RESULTS: Mean body surface area and median body mass index were 1.9 ± 0.2 m2 and 25.2 (23.4, 30.2) kg/m2. Mean CPB and median cross-clamping times were 107.7 ± 24.4 min and 64.5 (53, 75.8) min, and median CPB flow during cardioplegic arrest was 4 (3.6, 4.2) L/min (median cardiac index 2.1 [2, 2.2] L/min/m²). Venous drainage was considered sufficient by the surgeon in all cases, and insertion and removal were uncomplicated. Mean SvO2 during CPB was 80.2% ± 5.5%, and median peak lactate was 10 (8, 14) mg/dL, indicating sufficient perfusion. Mean venous negative drainage pressure during cross-clamping was 27.2 ± 12.3 mm Hg. Platelets dropped by 73.6 ± 37.5 K/µL, lactate dehydrogenase rose by 81.5 (44.3, 140.8) U/L, and leukocytes rose by 3.4 (2.2, 7.2) K/µL on postoperative day 1. CONCLUSIONS: The venous smart canula® allows for optimal venous drainage at low negative drainage pressures, facilitating sufficient perfusion in MICS.

Factors associated with an unsuccessful fast-track course following minimally invasive surgical mitral valve repair.

OBJECTIVES: Analyses of fast-track (FT) processes demonstrated that low-risk cardiac surgical patients require minimal intensive care, with a low incidence of mortality or morbidity. We investigated perioperative factors and their association with fast-track failure (FTF) in a retrospective cohort study of patients undergoing minimally invasive mitral valve surgery. METHODS: Patients undergoing minimally invasive surgical mitral valve repair for Carpentier type I or type II mitral regurgitation between 2014 and 2020 were included in the study. The definition of FTF consisted of >10 h mechanical ventilation, >24 h intensive care unit stay, reintubation after extubation and re-admission to the intensive care unit. Multivariable logistic regression analysis enabled the identification of factors associated with FTF. RESULTS: In total, 491 patients were included in the study and were analysed. Two hundred and thirty-seven patients (48.3%) failed the FT protocol. Multivariable logistic regression analysis showed that a New York Heart Association classification ≥III [odds ratio (OR) 2.05; 95% confidence interval (CI) 1.38-3.08; P < 0.001], pre-existing chronic kidney disease (OR 2.03; 95% CI 1.14-3.70; P = 0.018), coronary artery disease (OR 1.90; 95% CI 1.13-3.23; P = 0.016), postoperative bleeding requiring surgical revision (OR 8.36; 95% CI 2.81-36.01; P < 0.001) and procedure time (OR 1.01; 95% CI 1.01-1.01; P < 0.001) were independently associated with FTF. CONCLUSIONS: Factors associated with FTF in patients with Carpentier type I and II pathologies undergoing minimally invasive mitral valve repair are a New York Heart Association classification III-IV at baseline, pre-existing chronic kidney disease and coronary artery disease. Postoperative bleeding requiring rethoracotomy and procedure time were also identified as important factors associated with failed FT.

Interventional Procedures for Left Ventricular Assist Device-Associated Complications.

As patients on long-term left ventricular assist device (LVAD) face a substantial risk for open cardiac reoperation, interventional treatment approaches are becoming increasingly important in this population. We evaluated data of 871 patients who were on LVAD support between January 1, 2016 and December 1, 2020. Interventional treatments for LVAD-associated complications were performed in 76 patients. Seventeen patients underwent transcatheter aortic valve replacements (TAVR) and 61 patients underwent outflow graft interventions (OGI). TAVR improved symptoms in patients with severe symptomatic aortic regurgitation. Postinterventional complications included aggravation of preexisting right heart failure (RHF), third-degree atrioventricular block, and intrapump thrombosis (in 3 [16.7%], 2 [11.1%], and 1 [5.6%] patients, respectively). In outflow graft obstructions, OGI led to recovery of LVAD flow ( p < 0.001), unloading of the left ventricle ( p = 0.004), decrease of aortic valve opening time ( p = 0.010), and improvement of right heart function ( p < 0.001). Complications included bleeding, RHF, and others (in 9 [10.8%], 5 [6.0%], and 5 [6.0%] patients, respectively). Eight (9.6%) patients died within the hospital stay after OGI, including mortality secondary to prolonged cardiogenic shock. In conclusion, interventional procedures are a feasible and safe treatment modality for LVAD-associated complications.

Aortic valve replacement via right anterolateral minithoracotomy: preventing adverse events during the initial learning curve.

BACKGROUND: Despite excellent outcomes and reduced invasiveness, the right anterolateral thoracotomy approach for aortic valve replacement (RALT-AVR) has not been broadly adopted. This study provides results regarding the initial experience and learning curve of a single surgeon performing this procedure. METHODS: Periprocedural details and postoperative outcomes of the first 100 consecutive patients who underwent RALT-AVR at our institution were retrospectively analyzed. We conducted a cumulative sum analysis of surgical failure, defined as occurrence of 30-day-mortality, surgical revision for bleeding, conversion to sternotomy, 3rd degree heart block, paravalvular leakage, postoperative stroke or mean transvalvular gradient >20 mmHg. RESULTS: The cohort was of low surgical risk (mean EuroSCORE II 1.31%±0.85, mean STS PROM 1.45%±0.97), 58% were males. Median cross-clamp time was 67.5 (57.8-76) min, median CPB time 105 (91.8-119) min, and median operation time 164.5 (144.5-183.2) min. There were no conversions to full sternotomy, 4 cases of revision for bleeding and 2 pacemaker implantations for 3rd degree heart block. Prosthesis function was good (median ΔPmean 10.9 [7.4-13.6] mmHg). Thirty-day-mortality was 0%. The log-likelihood graph never crossed the upper boundary, and after a steady decrease, crossed the lower boundary at 93 patients. CONCLUSIONS: RALT-AVR can be performed with acceptable procedural times and satisfactory outcomes. For a well-trained surgeon, adapting to this new procedure does not expose patients to an increased risk, when patient selection and procedural planning are applied appropriately. Cumulative sum failure analysis is an appropriate tool to monitor the transition from standard AVR to the technically more demanding RALT-AVR.

SLL-PEEP Ventilation to Improve Exposure in Minimally Invasive Right Anterolateral Minithoracotomy Aortic Valve Replacement.

OBJECTIVE: An accepted landmark to assess feasibility of surgical aortic valve replacement (SAVR) via right anterolateral minithoracotomy (RALT) is the aortic-midpoint to right-sternal-edge distance. We aimed to evaluate single left lung positive-end-expiratory-pressure (SLL-PEEP) ventilation inducing an intraoperative rightward shift of the ascending aorta to improve exposure. METHODS: Nineteen patients with aortic stenosis undergoing SAVR via RALT were prospectively analyzed. SLL-PEEP ventilation (20,395 cmH2O) via a double-lumen endotracheal tube was applied immediately before transthoracic aortic cross-clamping, thereby inducing rightward shift of the ascending aorta to enhance exposure. We analyzed preoperative computed tomography (CT) reconstructions and intraoperative video recordings. Primary endpoint was extent of rightward shift induced by SLL-PEEP ventilation; secondary endpoints were procedure times and safety events. RESULTS: Mean age was 61 ± 14.8 years and 6 of 19 (31.6%) were female. Mean EuroSCORE II was 0.81% ± 0.04%, STS-PROM was 1.13% ± 0.74%, and mean aortic rightward shift induced by SLL-PEEP ventilation was 10.32 ± 4.14 mm (4 to 17 mm; P = 0.003). Median shift in the group considered suitable for the RALT approach by preoperative CT-scan evaluation was 14.2 mm (IQR 11) and in the less suitable group 11.5 mm (IQR 5). Mean procedure time was 167 ± 28.9 min, CPB time was 105.7 ± 18.4 min, and cross-clamp time was 64.5 ± 13 min. Fifteen patients (79%) received SAVR via RALT with implantation of a bioprosthesis, whereas a rapid-deployment-prosthesis was used in 4 patients (21%). Ten of 19 (53%) patients who were classified as less suitable preoperatively received SAVR via RALT after SLL-PEEP ventilation. No strokes were observed. CONCLUSIONS: The SLL-PEEP ventilation maneuver during SAVR via RALT significantly enhances aortic exposure. There were no safety events associated with this maneuver and we were able to demonstrate significant rightward aortic shift in every single patient.

State of the Art Review: Surgical Treatment of Acute Type A Aortic Dissection.

Acute type A aortic dissection (ATAAD) is a life-threatening event that requires immediate surgical treatment. Improvements in surgical treatment, graft technology, organ protection and imaging techniques have led to improved clinical outcomes. Individualized treatment concepts have emerged based on more advanced planning tools that allow for a tailored approach even in complex situations such as multi-level malperfusion. This review provides an overview of the current surgical treatment of ATAAD, focusing on new disease classifications, preoperative computed tomography angiography (CTA) assessment, new prosthesis and stent technologies, and organ-protection strategies.

Minimally invasive surgical aortic valve replacement through a right anterolateral thoracotomy.

In the field of minimally invasive surgical aortic valve replacement, the right anterolateral minithoracotomy is an approach that offers very limited procedural trauma. Our method of right anterolateral minithoracotomy uses femoral percutaneous cannulation, a high-definition thoracoscope and a transthoracic cross-clamp. It allows a minimized skin incision and full preservation of the sternum, sternocostal cartilages, and ribs. The patient we present in this video tutorial is a low-risk male with severe bicuspid aortic valve stenosis. We provide detailed insight into our preoperative planning and step-by-step guidance throughout the right anterolateral minithoracotomy aortic valve replacement procedure.

Preventing SARS-CoV-2 In-Hospital Infections in Cardiovascular Patients and Medical Staff: An Observational Study From the German Heart Center Berlin.

Objective: COVID-19 is a highly contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Preventing in-hospital infections is crucial to protect patients and hospital staff. Methods: At the very beginning of the COVID-19 pandemic, the German Heart Center initiated obligatory wearing of surgical face masks for patients and employees, SARS-CoV-2 screening for all patients, and symptom-based testing for employees. In addition, access restriction, closure of outpatient departments, and postponing non-urgent procedures were implemented with community-initiated regulations. Results: During the observation period (03/16/2020-04/27/2020), 1,128 SARS-CoV-2 tests were performed in 983 persons (1.1 tests/person; 589 in patients and 394 in hospital employees). Up to 60% of the clinical workforce was tested based on symptoms and risk (62.5% symptoms, 19.3% direct or indirect contact to known COVID-19, 4.5% returnee from risk area, 13.7% without specific reason). Patient testing for SARS-CoV-2 was obligatory (100% tested). The overall prevalence of positive tests during the observation period was 0.4% (n = 5 out of 1,128 tests performed). The incidence of new infections with SARS-CoV-2 was 0.5% (n = 5 out of 983 individuals; three healthcare workers, two patients). No nosocominal infections occurred, despite a mean number of 14.8 in-hospital contacts. Conclusion: Comprehensive SARS-CoV-2 testing and surgical face masks for patients and hospital staff, in addition to others measures, are key factors for the early detection of COVID-19 and to prevent spreading in the vulnerable hospital population.

Transcatheter Valve-in-Valve and Valve-in-Ring Interventions for Failing Bioprostheses and Annuloplasty Rings.

Transcatheter aortic valve implantation has dramatically changed the treatment of valvular heart disease over the past decade. At the same time, the indications for bioprosthesis implantation have been continuously extended toward younger patients, driven by excellent clinical results and improved durability. While the omission of oral anticoagulation reduces the risk of severe bleeding complications, the long-term durability of bioprostheses is still limited. In light of the growing number of elderly transcatheter aortic valve replacement (TAVR) patients, the prevalence of patients with failed bioprostheses and advanced comorbidities is expected to rise. Currently, transcatheter valve-in-valve (ViV) and valve-in-ring (ViR) interventions represent a valuable alternative treatment option for patients with a high risk for surgical reoperation. Several reports have described a high procedural success rate and low postprocedural morbidity and mortality during mid-term follow-up. We are still facing valve-specific and procedure-related challenges in all types of procedures, but especially in transcatheter ViR interventions. Considering the high technical demand of these interventions, a strong and highly specialized heart team in heart valve centers is the cornerstone of successful patient treatment. This review focuses on individualized patient selection, procedure-specific risk factors and technical aspects of transcatheter ViV/R interventions, and explores the currently available literature on postinterventional outcome.

Hypercapnia in late-phase ALI/ARDS: providing spontaneous breathing using pumpless extracorporeal lung assist.

OBJECTIVE: The fibroproliferative phase of late ALI/ARDS as described by Hudson and Hough (Clin Chest Med 27:671-677, 2006) is associated with pronounced reductions in pulmonary compliance and an accompanying hypercapnia complicating low tidal volume mechanical ventilation. We report the effects of extracorporeal CO(2) removal by means of a novel pumpless extracorporeal lung assist (p-ECLA) on tidal volumes, airway pressures, breathing patterns and sedation management in pneumonia patients during late-phase ARDS. DESIGN: Retrospective analysis. SETTING: Fourteen-bed university hospital ICU. PATIENTS: Ten consecutive late-phase ALI/ARDS patients with low pulmonary compliance, and severe hypercapnia. INTERVENTION: Gas exchange, tidal volumes, airway pressures, breathing patterns and sedation requirements before (baseline) and after (2-4 days) initiation of treatment with p-ECLA were analysed. Patients were ventilated in a pressure-controlled mode with PEEP adjusted to pre-defined oxygenation goals. MEASUREMENTS AND MAIN RESULTS: Median reduction in pCO(2) was 50% following institution of p-ECLA. Extracorporeal CO(2) removal enabled significant reduction in tidal volumes (to below 4 ml/kg predicted body weight) and inspiratory plateau pressures [30 (28.5/32.3) cmH(2)O, median 25, 75% percentiles]. Normalization of pCO(2) levels permitted significant reduction in the dosages of analgesics and sedatives. The proportion of assisted spontaneous breathing increased within 24 h of instituting p-ECLA. CONCLUSION: Elimination of CO(2) by p-ECLA therapy allowed reduction of ventilator-induced shear stress through ventilation with tidal volumes below 4 ml/kg predicted body weight in pneumonia patients with severely impaired pulmonary compliance during late-phase ARDS. p-ECLA treatment supported control of breathing pattern while sedation requirements were reduced and facilitated the implementation of assisted spontaneous breathing.

[Epidemiology and Pathophysiology of the acute respiratory distress syndrome (ARDS)]. / Epidemiologie und Pathophysiologie des akuten Lungenversagens (ARDS).

Despite the implementation of a multimodal concept of treatment, the acute respiratory distress syndrome (ARDS) is still afflicted with high mortality rates. A reasonable application and combination of possible treatment strategies, such as prone position, positive end-expiratory pressure (PEEP), restrictive volume therapy or nitric oxide (NO), requires pathophysiological and epidemiological knowledge. In the following article we describe basic pathophysiological parameters in development, progression and therapy of ARDS. Furthermore, we try to elucidate possible reasons for considerable limitations of multicentric studies in this field.

Influence of the hemoglobin solution HBOC-201 on tissue oxygenation in the rat R1H-tumor.

BACKGROUND: HBOC-201 is an ultra purified bovine hemoglobin solution. It has already been used in clinical phase II/III trials for emergency treatments. Animal experiments have shown that HBOC-201 is highly effective in tissue oxygenation. The study was performed in order to assess the potential of low dose HBOC-201 to improve tumor oxygenation. METHODS: 30 rats with a subcutaneously growing rhabdomyosarcoma R1H tumor were randomly assigned either to be ventilated with carbogen (n = 10), or to receive an IV injection of 0.3 g/kg HBOC-201 (n = 10) or a combination of 0.3 g/kg HBOC-201 and carbogen breathing (n = 10). Under general anesthesia the effects of the respective treatment on the tissue oxygen tension (tpO2) of the tumor were determined using a flexible stationary probe at baseline (b) and 15 and 60 min after application of the respective medication. RESULTS: HBOC-201 alone failed to improve tumor tpO2 (b: 1.3 +/- 1.2mmHg; 15min: 1.4 +/- 1 mmHg; 60min: 1 +/- 1 mmHg). In combination with carbogen the mean tpO2 of the tumor raised in comparison to baseline values (b: 3.1 +/- 4.6 mmHg; mmHg; 15min: 8.5 +/- 11*mmHg; 60min: 4.8 +/- 5mmHg; *p < 0.05 vs. b), but this effect was less pronounced than the increase in tpO2 by carbogen alone (b: 3.4 +/- 3.4mmHg; 15min: 9 +/- 10* mmHg; 60 min: 13 +/- 19* mmHg; *p < 0.05 vs. b). CONCLUSION: The application of low dose hemoglobin solution HBOC-201 does not result in improvement of tissue oxygenation in the rat rhabdomyosarcoma R1H.

No effect of the hemoglobin solution HBOC-201 on the response of the rat R1H tumor to fractionated irradiation.

BACKGROUND AND PURPOSE: Tumor hypoxia is regarded as one important underlying feature of radioresistance. The authors report on an experimental approach to improve tumor response to radiation by combining fractionated irradiation with HBOC-201, an ultrapurified polymerized hemoglobin solution, which is currently used in clinical phase II/III trials as alternative oxygen carrier and proved to be highly effective in tissue oxygenation (tpO(2)). MATERIAL AND METHODS: Subcutaneously growing rhabdomyosarcoma R1H tumors of the rat were treated with either 40 Gy (2 Gy/fraction, 20 fractions in 2 weeks, ambient) followed by graded top-up doses (clamped) alone, or in combination with HBOC-201, or with HBOC-201 plus carbogen (95% O(2) + 5% CO(2)). Local tumor control (TCD50%) and growth delay were used as endpoints. In addition, the effect of HBOC-201 alone or in combination with carbogen on the tpO(2) of tumor and muscle was determined using a flexible stationary probe (Licox, GMS). RESULTS: TCD50% values of 119 Gy (95% confidence interval 103;135), 111 Gy (84;138), and 102 Gy (83;120) were determined for tumors irradiated alone, in combination with HBOC-201, and with HBOC-201 plus carbogen, respectively. Although the dose-response curves showed a slight shift to lower doses when HBOC-201 or HBOC-201 plus carbogen was added, the differences in TCD50% were not statistically significant. No effect was seen on the growth delay of recurrent tumors. HBOC-201 alone did not effect tumor or muscle tpO(2). In combination with carbogen the mean tpO(2) of muscle raised from 23.9 mmHg to 59.3 mmHg (p < 0.05), but this effect was less pronounced than the increase in tpO(2) by carbogen alone. CONCLUSION: Low-dose application of HBOC-201 does not improve the response of the rhabdomyosarcoma R1H of the rat to fractionated irradiation.