Nils Haake

Detection of Diverse Bacterial Signatures in Atherosclerotic Lesions of Patients With Coronary Heart Disease

Background— Bacterial infection has been discussed as a potential etiologic factor in the pathophysiology of coronary heart disease (CHD). This study analyzes molecular phylogenies to systematically explore the presence, frequency, and diversity of bacteria in atherosclerotic lesions in patients with CHD. Methods and Results— We investigated 16S rDNA signatures in atherosclerotic tissue obtained through catheter-based atherectomy of 38 patients with CHD, control material from postmortem patients (n=15), and heart-beating organ donors (n=11) using clone libraries, denaturating gradient gel analysis, and fluorescence in situ hybridization. Bacterial DNA was found in all CHD patients by conserved PCR but not in control material or in any of the normal/unaffected coronary arteries. Presence of bacteria in atherosclerotic lesions was confirmed by fluorescence in situ hybridization. A high overall bacterial diversity of >50 different species, among them Staphylococcus species, Proteus vulgaris, Klebsiella pneumoniae, and Streptococcus species, was demonstrated in >1500 clones from a combined library and confirmed by denaturating gradient gel analysis. Mean bacterial diversity in atheromas was high, with a score of 12.33±3.81 (range, 5 to 22). A specific PCR detected Chlamydia species in 51.5% of CHD patients. Conclusions— Detection of a broad variety of molecular signatures in all CHD specimens suggests that diverse bacterial colonization may be more important than a single pathogen. Our observation does not allow us to conclude that bacteria are the causative agent in the etiopathogenesis of CHD. However, bacterial agents could have secondarily colonized atheromatous lesions and could act as an additional factor accelerating disease progression.

Postoperative neurocognitive dysfunction in patients undergoing cardiac surgery after remote ischemic preconditioning: a double-blind randomized controlled pilot study.

Background Remote ischemic preconditioning (RIPC) has been shown to enhance the tolerance of remote organs to cope with a subsequent ischemic event. We hypothesized that RIPC reduces postoperative neurocognitive dysfunction (POCD) in patients undergoing complex cardiac surgery. Methods We conducted a prospective, randomized, double-blind, controlled trial including 180 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass. Patients were randomized either to RIPC or to control group. Primary endpoint was postoperative neurocognitive dysfunction 5–7 days after surgery assessed by a comprehensive test battery. Cognitive change was assumed if the preoperative to postoperative difference in 2 or more tasks assessing different cognitive domains exceeded more than one SD (1 SD criterion) or if the combined Z score was 1.96 or greater (Z score criterion). Results According to 1 SD criterion, 52% of control and 46% of RIPC patients had cognitive deterioration 5–7 days after surgery (p = 0.753). The summarized Z score showed a trend to more cognitive decline in the control group (2.16±5.30) compared to the RIPC group (1.14±4.02; p = 0.228). Three months after surgery, incidence and severity of neurocognitive dysfunction did not differ between control and RIPC. RIPC tended to decrease postoperative troponin T release at both 12 hours [0.60 (0.19–1.94) µg/L vs. 0.48 (0.07–1.84) µg/L] and 24 hours after surgery [0.36 (0.14–1.89) µg/L vs. 0.26 (0.07–0.90) µg/L]. Conclusions We failed to demonstrate efficacy of a RIPC protocol with respect to incidence and severity of POCD and secondary outcome variables in patients undergoing a wide range of cardiac surgery. Therefore, definitive large-scale multicenter trials are needed. Trial Registration ClinicalTrials.gov NCT00877305

Automatic Control of Pressure Support for Ventilator Weaning in Surgical Intensive Care Patients

RATIONALE Despite its ability to reduce overall ventilation time, protocol-guided weaning from mechanical ventilation is not routinely used in daily clinical practice. Clinical implementation of weaning protocols could be facilitated by integration of knowledge-based, closed-loop controlled protocols into respirators. OBJECTIVES To determine whether automated weaning decreases overall ventilation time compared with weaning based on a standardized written protocol in an unselected surgical patient population. METHODS In this prospective controlled trial patients ventilated for longer than 9 hours were randomly allocated to receive either weaning with automatic control of pressure support ventilation (automated-weaning group) or weaning based on a standardized written protocol (control group) using the same ventilation mode. The primary end point of the study was overall ventilation time. MEASUREMENTS AND MAIN RESULTS Overall ventilation time (median [25th and 75th percentile]) did not significantly differ between the automated-weaning (31 [19-101] h; n = 150) and control groups (39 [20-118] h; n = 150; P = 0.178). Patients who underwent cardiac surgery (n = 132) exhibited significantly shorter overall ventilation times in the automated-weaning (24 [18-57] h) than in the control group (35 [20-93] h; P = 0.035). The automated-weaning group exhibited shorter ventilation times until the first spontaneous breathing trial (1 [0-15] vs. 9 [1-51] h; P = 0.001) and a trend toward fewer tracheostomies (17 vs. 28; P = 0.075). CONCLUSIONS Overall ventilation times did not significantly differ between weaning using automatic control of pressure support ventilation and weaning based on a standardized written protocol. Patients after cardiac surgery may benefit from automated weaning. Implementation of additional control variables besides the level of pressure support may further improve automated-weaning systems. Clinical trial registered with www.clinicaltrials.gov (NCT 00445289).

Is there really a clinical benefit of using minimized extracorporeal circulation for coronary artery bypass grafting

BACKGROUND Minimized extracorporeal circulation is intended to reduce the negative effects associated with cardiopulmonary bypass. This prospective study was performed to evaluate whether minimized extracorporeal circulation has a clinical benefit for coronary artery surgery patients compared to standard extracorporeal circulation. METHODS Sixty patients were randomized into two study groups: 30 patients underwent coronary artery bypass grafting using minimized extracorporeal circulation and 30 patients were operated using standard extracorporeal circulation. Baseline characteristics, intraoperative details, postoperative data, perioperative blood chemistry determinations of hematocrit, platelets, muscle-brain fraction of the creatine kinase, cardiac troponin T and colloid osmotic pressure as measurements of intrathoracic blood volume index and extravascular lung water index were compared. RESULTS Baseline characteristics and intraoperative details of both groups were similar. Patients who underwent minimized extracorporeal circulation showed more short-term dependency on norepinephrine ( P < 0.01). Their maximal postoperative muscle-brain fraction of the creatine kinase was lower ( P < 0.05) and their hematocrit on arrival in the intensive care unit was higher ( P < 0.01). No other significant differences were found. In both collectives, values for hematocrit ( P < 0.001), platelets ( P < 0.001), colloid osmotic pressure ( P < 0.001) and intrathoracic blood volume index ( P < 0.05) decreased, while the extravascular lung water index did not change significantly during cardiopulmonary bypass. CONCLUSIONS A clinical advantage of minimized over standard extracorporeal circulation was not found. Furthermore, a higher number of patients in the minimized extracorporeal circulation group required postoperative norepinephrine infusions for hemodynamic stabilization. In summary, the presumed superiority of minimized extracorporeal circulation for coronary artery bypass grafting in standard patients could not be confirmed.

Preoperative intra-aortic counterpulsation in high-risk patients undergoing cardiac surgery: a meta-analysis of randomized controlled trials

In contrast to the results of previous studies, recent randomized controlled trials (RCTs) failed to show a benefit of prophylactic aortic counterpulsation in high-risk patients undergoing cardiac surgery. The present analysis aims to redefine the effects of this treatment modality in the light of this new evidence. MEDLINE, EMBASE, CENTRAL/CCTR, Google Scholar and reference lists of relevant articles were searched for full-text articles of RCTs in English or German. Assessments for eligibility, relevance, study validity and data extraction were performed by two reviewers independently using prespecified criteria. The primary outcome was hospital mortality. A total of nine eligible RCTs with 1171 patients were identified: 577 patients were treated preoperatively with intra-aortic balloon pump (IABP) and 594 patients served as controls. The pooled odds ratio (OR) for hospital mortality (22 hospital deaths in the intervention arm, 54 in the control group) was 0.381 (95% CI 0.230-0.629; P < 0.001). The pooled analyses of five RCTs including only patients undergoing isolated on-pump coronary artery bypass grafting (n[IABP] = 348, n[control] = 347) also showed a statistically significant improvement in mortality for preoperative IABP implantation (fixed-effects model: OR 0.267, 95% CI 0.129-0.552, P < 0.001). The pooled OR for hospital mortality from two randomized off-pump trials was 0.556 (fixed-effects model, 95% CI 0.207-1.493, P = 0.226). Preoperative aortic counterpulsation was associated with a significant reduction in low cardiac output syndrome (LCOS) in the total population (fixed-effects model: OR 0.330, 95% CI 0.214-0.508, P < 0.001) as well as in the subgroup of CAGB patients (fixed-effects model: OR 0.113, 95% CI 0.056-0.226, P < 0.001), whereas there was no benefit in the off-pump population (fixed-effects model: OR 0.555, 95% CI 0.209-1.474, P = 0.238). Preoperative IABP implantation was associated with a reduction of intensive care unit (ICU) stay in all investigated populations with a greater effect in the total population [fixed-effects model: standard mean difference (SMD) -0.931 ± 0.198, P < 0.001] as well as in the subgroup of CAGB patients (fixed-effects model: SMD -1.240 ± 0.156, P < 0.001), compared with the off-pump group (fixed-effects model: SMD -0.723 ± 0.128, P < 0.001). Despite contradictory results from recent trials, the present study confirms the findings of previous meta-analyses that prophylactic aortic counterpulsation reduces hospital mortality, incidence of LCOS and ICU requirement in high-risk patients undergoing on-pump cardiac surgery. However, owing to small sample sizes and the lack of a clear-cut definition of high-risk patients, an adequately powered, prospective RCT is necessary to find a definite answer to the question, if certain groups of patients undergoing cardiac surgery benefit from a prophylactic IABP insertion.

Comparison of a continuous noninvasive arterial pressure device with invasive measurements in cardiovascular postsurgical intensive care patients: a prospective observational study.

BACKGROUND Arterial pressure monitoring using the a continuous noninvasive arterial pressure (CNAP) device during general anaesthesia is known to be interchangeable with continuous invasive arterial pressure (CIAP) monitoring. Agreement with invasive measurements in cardiovascular postsurgical intensive care patients has not been assessed. OBJECTIVE The objective of this study is to assess the agreement and interchangeability of CNAP with CIAP in cardiovascular postsurgical patients and to determine the effects of cardiac arrhythmia, catecholamine dosage, respiratory weaning and calibration intervals on agreement. DESIGN A prospective observational study. SETTING German university hospital cardiovascular ICU. Data were collected from April 2010 to December 2011. PATIENTS From 110 enrolled patients, 104 were included. Inclusion criteria were American Society of Anaesthesiologists (ASA) physical status III or IV patients undergoing controlled ventilation. Exclusion criteria included emergencies, complete heart block and marked arterial pressure differences greater than 10 mmHg in the two arms. MAIN OUTCOME MEASURES Bland–Altman plots, bias, precision, 95% limits of agreement, percentage error and agreement : tolerability indexes (ATIs) were estimated to determine clinical agreement. RESULTS From 11 222 arterial pressure readings, biases (SD) for CIAP-CNAP for systolic arterial pressure (SAP), diastolic arterial pressure (DAP) and mean arterial pressure (MAP) for all patients were 4.3 (11.6), −9.4 (8) and −6 (7.6) mmHg, respectively. Cardiac arrhythmia (4.1 (13.1), −14.4 (8.3), −9.5 (8.9) mmHg) and long interval to last calibration [4.5 (15), −9.8 (9.5), −6.4 (9.1) mmHg] impaired the accuracy of CNAP with failed interchangeability criteria defined by the percentage error. In contrast, use of catecholamines (epinephrine or norepinephrine infusions >0.1 &mgr;g kg−1 min−1), short calibration intervals and weaning conditions did not affect accuracy, interchangeability and agreement, especially of MAP. Agreement was defined as acceptable for MAP for all data and subgroups (ATI 0.8 to 1.0) and at worst, marginal for SAP and DAP (ATI 0.9 to 1.6). CONCLUSION CNAP showed acceptable agreement defined by the ATI with invasive measurements for MAP and partially for DAP, but there was considerable variability for SAP. MAP should be preferred for clinical decision making. Cardiac arrhythmia, in contrast to catecholamine dosage or weaning procedures, impaired the accuracy, agreement and interchangeability of CNAP. TRIAL REGISTRATION Clinical trials.gov identifier NCT01003665.

Dantrolene sodium improves the force–frequency relationship and β-adrenergic responsiveness in failing human myocardium

Failing human myocardium is characterized by a negative force–frequency relationship and impaired β‐adrenergic responsiveness which have been related to alterations of the intracellular Ca2 homeostasis. Dantrolene sodium is a clinically used drug that modulates myocardial Ca2 i handling in animal models. This study investigated the effects of dantrolene sodium on intracellular Ca2 handling and contractile function in failing human myocardium.

Predictors for long-term outcome and quality of life of patients after cardiac surgery with prolonged intensive care unit stay

OBJECTIVES This study investigated factors determining the long-term outcome and quality of life of patients with a prolonged intensive care unit (ICU) stay after cardiac surgery. DESIGN A retrospective analysis was performed in 230 patients that had undergone cardiac surgery and suffered from a post-operative ICU stay of 7 or more days at our institution. Among 11 pre-, 13 intra-, and 14 post-operative variables, factors influencing 5-year outcome were identified by logistic regression analysis. Quality of life was determined using the Short Form-36 questionnaire. RESULTS In-hospital mortality was 12%. One hundred and eleven of 187 patients (59%) were alive after 5 years. Non-survivors were older (70 vs. 65 years, p = 0.005) and had a higher additive EuroSCORE (7 vs. 5, p = 0.034). Logistic regression identified pre-operative atrial fibrillation (AF), (28 vs. 10%, p = 0.003) as the strongest predictor for a 5-year outcome, followed by myocardial infarction (62 vs. 41%, p = 0.005), and prolonged mechanical ventilation (8 vs. 5 days, p = 0.036). Survivors did not show an impaired physical component summary SF-36 score (39 vs. 46, p = 0.737) or mental component summary score (55 vs. 55, p = 0.947) compared to an age-matched German Normative Sample. CONCLUSIONS Pre-operative AF proved to be the most important factor determining the 5-year outcome of patients with a prolonged ICU stay after cardiac surgery. Neither physical nor mental health appeared to be impaired in these patients.

Is universal antifungal prophylaxis mandatory in adults after lung transplantation? A review and meta-analysis of observational studies.

Lung transplant (LTX) recipients are at high risk of invasive Aspergillus infections (IAI). However, no randomized‐controlled trials (RCT) or international guidelines on antifungal prophylaxis (AFP) in the LTX population exist.

Impact of the Eurotransplant High-Urgency Heart Allocation System on the Outcome of Transplant Candidates in Germany

BACKGROUND In 2000, the Eurotransplant Foundation changed the allocation criteria following the enactment of the German Transplantation Law (GTL). Our study investigated the impact of the new allocation system on outcomes after heart transplantation (HTx) in Germany. METHODS We compared 2 cohorts of patients who underwent HTx at our institution in two different 3-year periods before (Group 1: 01/1995-12/1997) and after (Group 2: 01/2003-12/2005) implementation of the new system. RESULTS An increase in the ratio of HTx performed on an urgency basis was found in Group 2 (8.3 % vs. 87.2 %; P < 0.001). The median waiting time and the ischemia time were significantly lower in Group 1 ( P < 0.05). Postoperatively, the length of ICU stay was significantly higher in Group 2 ( P = 0.04). CONCLUSION The new allocation system decreased the proportion of local and regional organ harvesting. It generates a higher ischemia time without increasing the number of transplantations and without improving the clinical outcome after HTx. The severity of heart failure, rate of secondary organ impairment, and comorbidity is markedly elevated in patients waiting for HTx on HU.