Incidence of Hypocapnia, Hypercapnia, and Acidosis and the Associated Risk of Adverse Events in Preterm Neonates.

BACKGROUND: Permissive hypercapnia is a lung-protection strategy. We sought to review our current clinical practice for the range of permissive hypercapnia and identify the relationship between PaCO2 and pH and adverse outcomes. METHODS: A secondary analysis of a delayed cord-clamping clinical trial was performed on all arterial blood gas tests in the first 72 h in infants < 32 weeks gestational age. All arterial blood gas values were categorized into a clinical range to determine the percent likelihood of occurring in the total sample. The univariate and multivariate relationships of severe adverse events and the time-weighted PaCO2 , fluctuation of PaCO2 , maximal and minimal PaCO2 , base excess, and pH were assessed. RESULTS: 147 infants with birthweight of 1,206 ± 395 g and gestational age of 28 ± 2 weeks were included. Of the 1,316 total samples, < 2% had hypocapnia (PaCO2 <30 mm Hg), 47% were normocapnic (PaCO2 35-45 mm Hg), 26.5% had mild hypercapnia (PaCO2 45-55 mm Hg), 13% had moderate hypercapnia (PaCO2 55-65 mm Hg), and 6.5% had severe hypercapnia (PaCO2 ≥ 65 mm Hg). There were no adverse events associated with hypocapnia. Subjects with death/severe intraventricular hemorrhage had a higher mean PaCO2 of 52.3 versus 44.7 (odds ratio [OR] 1.16, 95% CI 1.04-1.29, P = .006), higher variability of PaCO2 with a standard deviation of 12.6 versus 7.8 (OR 1.15, 95% CI 1.03-1.27, P = .01), and a lower minimum pH of 7.03 versus 7.23 (OR 0, 95% CI 0-0.06, P = .003). There was no significant difference in any variables in subjects who developed other adverse events. CONCLUSION: The routine targeting of higher than normal PaCO2 goals may lead to a low incidence of hypocapnia and associated adverse events. Hypercapnia is common, and moderate hypercapnia may increase the risk of neurologic injury and provide little pulmonary benefit.

The Neu-Prem Trial: Neuromonitoring of Brains of Infants Born Preterm During Resuscitation-A Prospective Observational Cohort Study.

OBJECTIVE: To determine whether monitoring cerebral oxygen tissue saturation (StO2) with near-infrared spectroscopy (NIRS) and brain activity with amplitude-integrated electroencephalography (aEEG) can predict infants at risk for intraventricular hemorrhage (IVH) and death in the first 72 hours of life. STUDY DESIGN: A NIRS sensor and electroencephalography leads were placed on 127 newborns <32 weeks of gestational age at birth. Ten minutes of continuous NIRS and aEEG along with heart rate, peripheral arterial oxygen saturation, fraction of inspired oxygen, and mean airway pressure measurements were obtained in the delivery room. Once the infant was transferred to the neonatal intensive care unit, NIRS, aEEG, and vital signs were recorded until 72 hours of life. An ultrasound scan of the head was performed within the first 12 hours of life and again at 72 hours of life. RESULTS: Thirteen of the infants developed any IVH or died; of these, 4 developed severe IVH (grade 3-4) within 72 hours. There were no differences in either cerebral StO2 or aEEG in the infants with low-grade IVH. Infants who developed severe IVH or death had significantly lower cerebral StO2 from 8 to 10 minutes of life. CONCLUSIONS: aEEG was not predictive of IVH or death in the delivery room or in the neonatal intensive care unit. It may be possible to use NIRS in the delivery room to predict severe IVH and early death. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605733.

Delayed Cord Clamping in Newborns Born at Term at Risk for Resuscitation: A Feasibility Randomized Clinical Trial.

Infants may benefit if resuscitation could be provided with an intact umbilical cord. Infants identified at risk for resuscitation were randomized to 1- or 5-minute cord clamping. The 5-minute group had greater cerebral oxygenation and blood pressure. Studies are needed to determine whether this translates into improved outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02827409.

Treatment of gram-positive deep sternal wound infections in cardiac surgery--experiences with daptomycin.

The reported incidence of deep sternal wound infection (DSWI) after cardiac surgery is 0.4-5% with Staphylococcus aureus being the most common pathogen isolated from infected wound sternotomies and bacteraemic blood cultures. This infection is associated with a higher morbidity and mortality than other known aetiologies. Little is reported about the optimal antibiotic management. The aim of the study is to quantify the application of daptomycin treatment of DSWI due to gram-positive organisms post cardiac surgery. We performed an observational analysis in 23 cases of post sternotomy DSWI with gram-positive organisms February 2009 and September 2010. When the wound appeared viable and the microbiological cultures were negative, the technique of chest closure was individualised to the patient. The incidence of DSWI was 1.46%. The mean dose of daptomycin application was 4.4 ± 0.9 mg/kg/d and the average duration of the daptomycin application was 14.47 ± 7.33 days. In 89% of the patients VAC therapy was used. The duration from daptomycin application to sternal closure was 18 ± 13.9 days. The parameters of infection including, fibrinogen (p = 0.03), white blood cell count (p = 0.001) and C-reactive protein (p = 0.0001) were significantly reduced after daptomycin application. We had no mortality and wound healing was successfully achieved in all patients. Treatment of DSWI due to gram-positive organisms with a daptomycin-containing antibiotic regimen is safe, effective and promotes immediate improvement of local wound conditions.Based on these observations, daptomycin may offer a new treatment option for expediting surgical management of DSWI after cardiac surgery.

Relation between renal dysfunction requiring renal replacement therapy and promoter polymorphism of the erythropoietin gene in cardiac surgery.

Several genetic polymorphisms have been identified to play a role in the occurrence and progression of renal dysfunction after cardiac surgery with cardiopulmonary bypass (CPB). Recently, it was demonstrated that the T allele of SNP rs1617640 in the promoter of the erythropoetin (EPO) gene is significantly associated with proliferative diabetic retinopathy (PDR) and end-stage renal disease (ESRD) due to increased EPO expression. This disease risk-associated gene and its potential pathway mediating severe microvascular complications in T-allele carriers could also play a role on renal dysfunction in patients who underwent cardiac surgery with CPB. We hypothesized that the patients' ability to produce increased EPO concentrations will affect morbidity and mortality after CPB. We conducted a prospective single center study between April 2006 and May 2007. In 481 patients who underwent cardiac surgery with CPB we prospectively examined the SNP rs1617640 in the promoter of the EPO gene by DNA sequencing. The patients were grouped according to their genotype (GG, GT, and TT). The genotype distribution of SNP rs1617640 in the promoter of the EPO gene was 36% (TT), 49% (TG), and 15% (GG). There was no difference in age, body mass index, gender, CPB time, or length of stay in intensive care unit. The hospitalization was irrespective of the patients' genotypes. The baseline creatinine in the TT group was 0.2 points higher than in the other groups; however this was without statistical significance in the multivariate analysis. No significant difference was shown in Euroscore, the Simplified Acute Physiology Score II, the Acute Physiology and Chronic Health Evaluation Score II, Acute Renal Failure Score, or the Risk, Injury, Failure, Loss of Kidney Function Score. The mortality was equal across the genotypes. However, an association between the TT genotype and acute renal replacement therapy (P=0.03), intra-aortic balloon pump usage (P=0.02), and serum creatine phosphokinase-MB increase (P=0.03) were observed after cardiac surgery. Our analysis suggests that the risk allele (T) of rs1617640 plays a role in the development of renal dysfunction after cardiac surgery with CPB. Patients with the TT risk allele required more frequent acute renal replacement therapy. Since our result is close to the border of significance, this hypothesis should be investigated in larger prospective studies with long-term follow-up to emphasize this polymorphism as a potential risk factor.

The role of phospho-adenosine monophosphate-activated protein kinase and vascular endothelial growth factor in a model of chronic heart failure.

We established a stable and reproducible animal model of chronic heart failure (CHF) in sheep to investigate biomolecular changes. Therefore, two biomarkers, adenosine monophosphate-activated protein kinase (AMPK) and vascular endothelial growth factor-A (VEGF-A) were examined to reveal their role during chronic ischemic conditions of the heart. AMPK was studied because it plays an important role in cellular energy homeostasis and its upregulation is associated with myocardial ischemia, whereas VEGF-A was studied because it acts as an important signaling protein for neoangiogenesis. We examined 15 juvenile sheep (mean weight, 78±4kg; control, n=3; ShamOP, n=2; coronary microembolization [CME], n=10). CHF was induced under fluoroscopic guidance by multiple sequential microembolizations (MEs) through bolus injection of polysterol microspheres (90µm, n=25.000) into the left main coronary artery. CME was repeated up to three times at 2- to 3-week intervals until animals started to develop stable signs of CHF. All animals were followed for 3 months. Phosphorylation of AMPK, marking the activated protein form, was detected by Western blotting. VEGF-A and vascular endothelial growth factor-receptor 2 (VEGF-R2) mRNA were detected by real-time polymerase chain reaction. Glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) was used as a reference housekeeping gene. All 10 CHF animals developed clinical signs of CHF as indicated by a significant decrease of cardiac output, decreased ejection fraction, as well as occurrence of tachycardia and tachypnoea. Western blots showed significant phosphorylation of AMPK in CME animals compared to the control group (phospho-adenosine monophosphate-activated protein kinase α) (GAPDH control: 0.0, CME left ventricle [LV]: 0.39±0.20, CME right ventricle [RV]: 0.53±0.30; P<0.05). VEGF-A and VEGF-R2 expression in CME animal myocardium was within the range of the control group, but this data did not reach statistical significance due to the small size of this group. While microinjection was performed into the left main coronary artery, phosphorylation of AMPK and expression of VEGF-A and VEGF-R2 were significantly higher in the RV than in the LV. Multiple sequential intracoronary MEs can effectively induce myocardial dysfunction with clinical and biomolecular signs of chronic ischemic cardiomyopathy. Quantitative analysis of biomolecular markers showed a significantly higher phosphorylation of AMPK in CHF animals compared with control myocardium.

Extracorporeal life support in pediatric cardiac dysfunction.

BACKGROUND: Low cardiac output (LCO) after corrective surgery remains a serious complication in pediatric congenital heart diseases (CHD). In the case of refractory LCO, extra corporeal life support (ECLS) extra corporeal membrane oxygenation (ECMO) or ventricle assist devices (VAD) is the final therapeutic option. In the present study we have reviewed the outcomes of pediatric patients after corrective surgery necessitating ECLS and compared outcomes with pediatric patients necessitating ECLS because of dilatated cardiomyopathy (DCM). METHODS: A retrospective single-centre cohort study was evaluated in pediatric patients, between 1991 and 2008, that required ECLS. A total of 48 patients received ECLS, of which 23 were male and 25 female. The indications for ECLS included CHD in 32 patients and DCM in 16 patients. RESULTS: The mean age was 1.2 ± 3.9 years for CHD patients and 10.4 ± 5.8 years for DCM patients. Twenty-six patients received ECMO and 22 patients received VAD. A total of 15 patients out of 48 survived, 8 were discharged after myocardial recovery and 7 were discharged after successful heart transplantation. The overall mortality in patients with extracorporeal life support was 68%. CONCLUSION: Although the use of ECLS shows a significantly high mortality rate it remains the ultimate chance for children. For better results, ECLS should be initiated in the operating room or shortly thereafter. Bridge to heart transplantation should be considered if there is no improvement in cardiac function to avoid irreversible multiorgan failure (MFO).

Morphological investigations of type A aortic dissection.

PURPOSE: The aim of this study was to analyze systematically the morphology of aortal segments of Type A dissection. METHODS: Nineteen patients were operated on for Type A dissection in the Department of Thoracic, Cardiac, and Vascular Surgery in Goettingen, Germany, from January 2002 to January 2005. All diagnoses were confirmed by transesophageal echocardiography and computed tomography of the chest. All taken aortic segments were examined by the conventional histological and electron microscopical method. RESULTS: Besides subadventitial hyperplasia of collagen filaments, the preparations showed hyperplasia of endothelial cells with loose cellular junctions, desquamation of endothelial cells, and morphological changes of endothelial cells with villius development, as well as signs of aortitis. CONCLUSION: The present results arouse suspicion of local inflammation of the aortic wall, but with moderate progress under strong hyperplasia. Because of rupture of the intima, the inflammation appears as an acute disease.

Daptomycin as a possible new treatment option for surgical management of Methicillin-Resistant Staphylococcus aureus sternal wound infection after cardiac surgery.

We present a case of a 77-year old female who had undergone a coronary artery bypass grafting with an aortic valve replacement and developed three month later a Methicillin-Resistant Staphylococcus aureus (MRSA) sternal wound infection which was successful treated with Daptomycin combined with vacuum-assisted closure (VAC).

Bentall procedure 39 years after implantation of a Starr-Edwards aortic caged-ball-valve prosthesis.

We report a case of a male patient who received an implantation of a Starr-Edwards-caged-ball-valve-prosthesis in 1967. The surgery and postoperative course were without complications and the patient recovered well after the operation. For the next four decades, the patient remained asymptomatic--no restrictions on his lifestyle and without any complications. In 2006, 39 years after the initial operation, we performed a Bentall-Procedure to treat an aortic ascendens aneurysm with diameters of 6.0 x 6.5 cm: we explanted the old Starr-Edwards-aortic-caged-ball-valve-prosthesis and replaced the ascending aorta with a 29 mm St.Jude Medical aortic-valve-composite-graft and re-implanted the coronary arteries.This case represents the longest time period between Starr-Edwards-caged-ball-valve-prosthesis-implantation and Bentall-reoperation, thereby confirming the excellent durability of this valve.

CABG surgery with long coronary endarterectomy of the LAD.

Diffuse atherosclerosis of the anterior descending artery may require unconventional surgical treatment to increase graft flow. A 74-year-old man with severe, diffuse 3-vessel-coronary artery disease was presented to our institution with progredient angina pectoris symptoms. Intraoperatively, the revascularization of the left anterior descending coronary artery (LAD) was technically challenging because of the extremely calcified coronary artery disease; therefore we performed the longest endarterectomy of the LAD that has thus far been described.

AMPK - Activated Protein Kinase and its Role in Energy Metabolism of the Heart.

Adenosine monophosphate - activated kinase (AMPK) plays a key role in the coordination of the heart's anabolic and catabolic pathways. It induces a cellular cascade at the center of maintaining energy homeostasis in the cardiomyocytes.. The activated AMPK is a heterotrimeric protein, separated into a catalytic α - subunit (63kDa), a regulating ß - subunit (38kDa) and a γ - subunit (38kDa), which is allosterically adjusted by adenosine triphosphate (ATP) and adenosine monophosphate (AMP). The actual binding of AMP to the γ - subunit is the step which activates AMPK. AMPK serves also as a protein kinase in several metabolic pathways of the heart, including cellular energy sensoring or cardiovascular protection. The AMPK cascade represents a sensitive system, activated by cellular stresses that deplete ATP and acts as an indicator of intracellular ATP/AMP. In the context of cellular stressors (i.e. hypoxia, pressure overload, hypertrophy or ATP deficiency) the increasing levels of AMP promote allosteric activation and phosphorylation of AMPK. As the concentration of AMP begins to increase, ATP competitively inhibits further phosphorylation of AMPK. The increase of AMP may also be induced either from an iatrogenic emboli, percutaneous coronary intervention, or from atherosclerotic plaque rupture leading to an ischemia in the microcirculation. To modulate energy metabolism by phosphorylation and dephosphorylation is vital in terms of ATP usage, maintaining transmembrane transporters and preserving membrane potential. In this article, we review AMPK and its role as an important regulatory enzyme during periods of myocardial stress, regulating energy metabolism, protein synthesis and cardiovascular protection.

Daptomycin for treatment of methicillin-resistant Staphylococcus epidermidis saphenectomy wound infection after coronary artery bypass graft operation (CABG): a case report.

We report a case of successful treatment of postoperative saphenectomy wound infection of the upper left leg with the antibiotic drug Daptomycin.

Myocardial ischemia with left ventricular outflow obstruction.

We report an unusual case of a 32-year old man who was treated for a hypertrophic obstructive cardiomyopathy (HOCM) with a DDD pacing with short AV delay reduction in the past. Without prior notice the patient developed ventricular fibrillation and an invasive cardiac diagnostic was performed, which revealed a myocardial bridging around of the left anterior descending artery (LAD). We suspected ischemia that could be either related to LAD artery compression or perfusion abnormalities due to AV delay reduction with related to diastolic dysfunction.

Early results of coronary artery bypass grafting with coronary endarterectomy for severe coronary artery disease.

BACKGROUND: Despite the existence of controversial debates on the efficiency of coronary endarterectomy (CE), it is still used as an adjunct to coronary artery bypass grafting (CABG). This is particularly true in patients with endstage coronary artery disease. Given the improvements in cardiac surgery and postoperative care, as well as the rising number of elderly patient with numerous co-morbidities, re-evaluating the pros and cons of this technique is needed. METHODS: Patient demographic information, operative details and outcome data of 104 patients with diffuse calcified coronary artery disease were retrospectively analyzed with respect to functional capacity (NYHA), angina pectoris (CCS) and mortality. Actuarial survival was reported using a Kaplan-Meyer analysis. RESULTS: Between August 2001 and March 2005, 104 patients underwent coronary artery bypass grafting (CABG) with adjunctive coronary endarterectomy (CE) in the Department of Thoracic-, Cardiac- and Vascular Surgery, University of Goettingen. Four patients were lost during follow-up. Data were gained from 88 male and 12 female patients; mean age was 65.5 +/- 9 years. A total of 396 vessels were bypassed (4 +/- 0.9 vessels per patient). In 98% left internal thoracic artery (LITA) was used as arterial bypass graft and a total of 114 vessels were endarterectomized. CE was performed on right coronary artery (RCA) (n = 55), on left anterior descending artery (LAD) (n = 52) and circumflex artery (RCX) (n = 7). Ninety-five patients suffered from 3-vessel-disease, 3 from 2-vessel- and 2 from 1-vessel-disease. Closed technique was used in 18%, open technique in 79% and in 3% a combination of both. The most frequent endarterectomized localization was right coronary artery (RCA = 55%). Despite the severity of endstage atherosclerosis, hospital mortality was only 5% (n = 5). During follow-up (24.5 +/- 13.4 months), which is 96% complete (4 patients were lost caused by unknown address) 8 patients died (cardiac failure: 3; stroke: 1; cancer: 1; unknown reasons: 3). NYHA-classification significantly improved after CABG with CE from 2.2 +/- 0.9 preoperative to 1.7 +/- 0.9 postoperative. CCS also changed from 2.4 +/- 1.0 to 1.5 +/- 0.8 CONCLUSION: Early results of coronary endarterectomy are acceptable with respect to mortality, NYHA & CCS. This technique offers a valuable surgical option for patients with endstage coronary artery disease in whom complete revascularization otherwise can not be obtained. Careful patient selection will be necessary to assure the long-term benefit of this procedure.