Anticoagulation After Biological Aortic Valve Replacement: Is There An Optimal Regimen?

BACKGROUND: The anticoagulation of biological heart valves remains a 'hot spot' of discussion in various domains due to the risk of developing valve thrombosis and arterial thromboembolism. The situation has always been controversial, especially during the early postoperative phase. The American College of Cardiology/ American Heart Association and European Society of Cardiology guidelines recommend the use of warfarin for the first three months after biological aortic valve replacement (BAVR), although the American College of Chest Physicians guidelines suggest that these recommendations are experience-based and that the risk/benefit is unclear. The aim of the present study was to compare the efficacy of aspirin and warfarin in patients after BAVR. METHODS: A total of 863 patients who underwent BAVR between 2008 and 2015 was allocated to two groups. Each group was managed with a specific anticoagulation regimen, with 430 patients receiving warfarin during the first three postoperative months, and 433 receiving aspirin. The major study end points were bleeding, cerebral ischemic events, and survival. RESULTS: In total, 10 and 15 postoperative cerebral ischemic events occurred between 24 h and three months after surgery in patients treated with aspirin and warfarin, respectively. After three months the incidence of cerebral ischemic events did not differ greatly between the two groups. The rate of major bleeding events and rates of stroke-free survival and overall survival were not statistically significant between the warfarin and aspirin groups. CONCLUSIONS: Plasma anticoagulation with warfarin during the early postoperative phase was shown statistically to be inferior to platelet aggregation inhibition by aspirin with regards to postoperative bleeding risk, cerebral ischemic events, and survival.

Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis: The HYPRESS Randomized Clinical Trial.

Importance: Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. Objective: To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. Design, Setting, and Participants: Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. Interventions: Patients were randomly allocated 1:1 either to receive a continuous infusion of 200 mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). Main Outcomes and Measures: The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level >150 mg/dL [to convert to millimoles per liter, multiply by 0.0555]). Results: The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. Conclusions and Relevance: Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients. Trial Registration: clinicaltrials.gov Identifier: NCT00670254.

Impairment of renal function using hyperoncotic colloids in a two hit model of shock: a prospective randomized study.

INTRODUCTION: One of the therapeutic essentials in severe sepsis and septic shock is an adequate fluid replacement to restore and maintain circulating plasma volume, improve organ perfusion and nutritive microcirculatory flow. The type of solution to be used as a fluid replacement remains under discussion. The aim of the study was to evaluate the effects of clinically used fluid replacement solutions on renal function and inflammatory response. METHODS: A total of 23 anesthetized and ventilated female German Landrace pigs were investigated over 19 hours using a two-hit model that combined hemorrhagic and septic shock. The septic shock was induced using an Escherichia coli laden clot placed into the abdominal cavity. Infusions of 6% hydroxyethylstarch 130/0.42 in acetate (6% HES 130), 4% gelatin in acetate (4% gelatin) and 10% hydroxyethylstarch 200/0.5 in saline (10% HES200) compared to Ringer's acetate (RAc) were used for fluid replacement to maintain a central venous pressure of 12 mmHg. Ringer's acetate was also used in the sham-treated group (SHAM). RESULTS: At study end the cardiac output (10% HES200 143±48 ml/kgBW; 6% HES130 171±47 ml/kgBW; RAc 137±32 ml/kgBW; 4% gelatin 160±42 ml/kgBW), as well as mean arterial pressure did not differ between groups. N-acetyl-beta-D-glucosamidase was significantly higher in the hydroxyethylstarch 200 (157±115 U/g creatinine; P<0.05) group compared to hydroxyethylstarch 130 (24±9 U/g creatinine), Ringer's acetate (2±3 U/g creatinine) and SHAM (21±15 U/g creatinine) at the study's end. Creatinine significantly increased by 87±84 percent of baseline in the 10% HES200 group compared to RAc and 6% HES130. We demonstrated in the histology of the kidneys a significant increase in osmotic-nephrosis like lesions for 4% gelatin compared to RAc, 6% HES130 and SHAM. Urine output was lowest in the 10% HES200 and 4% gelatin group, however not significantly.Interleukin(IL)-6 levels were significantly elevated in the 10% HES200 group (3,845±1,472 pg/ml) two hours after sepsis induction compared to all other groups (6% HES130 1,492±604 pg/ml; RAc 874±363 pg/ml; 4% gelatin 1,623±1,242 pg/ml). CONCLUSIONS: Despite similar maintenance of macrocirculation 6% hydroxyethylstarch 130/0.42 and Ringer's acetate significantly preserve renal function and attenuate tubular damage better than 10% hydroxyethylstarch 200/0.5 in saline.

Hydroxyethylstarch impairs renal function and induces interstitial proliferation, macrophage infiltration and tubular damage in an isolated renal perfusion model.

INTRODUCTION: The aim of the study was to evaluate some of the underlying pathomechanisms of hydroxyethylstarch (HES) induced adverse effects on renal function using 24 porcine kidneys in an isolated perfusion model over six hours. METHODS: Infusion of either 10% HES 200/0.5, 6% HES 130/0.42 or Ringer's lactate (RL) was performed to achieve an haematocrit of 20% in eight kidneys from four animals per group. Physiological and pathophysiological parameters were determined (including N-acetyl-beta-aminoglucosidase as a marker for lysosomal tubular damage). Histological investigations and immunohistological stainings of the kidneys were performed. RESULTS: Initially after haemodilution, HES 130/0.42 and HES 200/0.5 reduced urine output compared with RL (P < 0.01). After six hours, N-acetyl-beta-aminoglucosidase was significantly higher in HES 200/0.5 (81 +/- 23 U/L) compared with HES 130/0.42 (38 +/- 12 U/L) and RL (21 +/- 13 U/L; P < 0.001). Osmotic nephrosis-like lesions (OL) of the tubuli were present in all groups showing a significantly lower number of OL in RL (1.1 +/- 0.4; P = 0.002) compared with both HES groups (HES 200/0.5 = 2.1 +/- 0.6; HES 130/0.42 = 2.0 +/- 0.5). Macrophage infiltration was significantly higher in HES 200/0.5 compared with HES 130/0.42 (1.3 +/- 1.0 vs. 0.2 +/- 0.04; P = 0.044). There was a significant increase in interstitial cell proliferation in the HES 200/0.5 group vs. HES 130/0.42 (18.0 +/- 6.9 vs. 6.5 +/- 1.6; P = 0.006) with no significant difference in RL (13.5 +/- 4.0). CONCLUSIONS: We observed impaired diuresis and sodium excretion by HES and identified renal interstitial proliferation, macrophage infiltration and tubular damage as potential pathological mechanisms of HES-induced adverse effects on renal function using an isolated porcine renal perfusion model. Furthermore, we demonstrated that 10% HES 200/0.5 had more of a pro-inflammatory effect compared with 6% HES 130/0.42 and caused more pronounced tubular damage than 6% HES 130/0.42 and RL. OL were present in all groups, but to a lesser degree after RL administration.

Measurement of cardiac output in ventricular rupture following acute myocardial infarction--pulmonary artery catheter vs transpulmonary thermodilution--a case report.

We compared the cardiac output measured by the transpulmonary aortic single indicator thermodilution method with that by the pulmonary artery catheterization in a patient with ventricular septal rupture after acute myocardial infarction. Though the former cardiac output was lower than the latter, in the presence of the ventricular septal rupture, the cardiac outputs were equal after the rupture was closed. This indicates that, while the cardiac output measured by the pulmonary artery catheter is influenced by the ventricular left-to-right shunt, transpulmonary aortic thermodilution method measures the true cardiac output of the left heart, which is responsible for organ perfusion.

Low-dose intravenous midazolam reduces etomidate-induced myoclonus: a prospective, randomized study in patients undergoing elective cardioversion.

BACKGROUND: Myoclonic movements are a common problem in unpremedicated patients during induction of anesthesia with etomidate. METHODS: In a double-blind fashion, 40 patients (ASA physical status III-IV) scheduled for elective cardioversion were randomly assigned to receive either 0.015 mg/kg midazolam or placebo 90 s before the injection of 0.3 mg/kg etomidate. Myoclonic movements and sedation were recorded on a scale between 0 and 3. Pulse oximetry, noninvasive arterial blood pressure, and heart rate were recorded during the study period. RESULTS: Two patients (10%) in the midazolam group had myoclonic movements after the administration of etomidate, whereas 10 of the 20 patients (50%) receiving placebo experienced such movements (P = 0.006). No other differences were found between the groups; in particular, there was no difference in recovery 5 min after the administration of etomidate. CONCLUSIONS: IV midazolam 0.015 mg/kg administered 90 s before induction of anesthesia with etomidate is effective in reducing myoclonic movements and does not prolong recovery in unpremedicated patients after short procedures.

Percutaneous transtracheal ventilation: effects of a new oxygen flow modulator on oxygenation and ventilation in pigs compared with a hand triggered emergency jet injector.

The application of percutaneous transtracheal jet ventilation for emergency ventilation depends on special equipment which is often not available outside the operating room. The oxygen flow modulator is a new specially designed device for emergency ventilation using a low pressure oxygen supply. We studied the effects of the new device in comparison with a hand triggered emergency jet injector on oxygenation and ventilation in six pigs (21+/-1 kg). The animals were anaesthetized, tracheally intubated, and mechanically ventilated. Following central venous and pulmonary artery catheterization, a Paratrend 7 sensor was placed in the left femoral artery for continuous measurements of PaO(2) and PaCO(2). Then an emergency transtracheal airway catheter was inserted into the trachea after surgical exposure. In randomized order each animal was ventilated via the transtracheal airway catheter with the hand triggered emergency jet injector (inspiratory/expiratory (I/E) ratio of 1:1; respiratory rate of 60 min(-1); driving pressure 1.5 bar; FjetO(2) 1.0) and the oxygen flow modulator (FiO(2) 1.0 at an oxygen flow of 15 l min(-1); respiratory rate of 60 min(-1); I/E ratio of approximately 1:1) for 15 min each. After each phase of the experiment respiratory and hemodynamic variables were measured. Whereas PaO(2) was not significantly different between the two devices, PaCO(2) was higher during the hand-triggered jet ventilation. Thus, the efficacy of the oxygen flow modulator during the experiment was comparable with the efficacy of the hand triggered emergency jet injector.

Arterial pressure-based cardiac output monitoring: a multicenter validation of the third-generation software in septic patients.

PURPOSE: Second-generation FloTrac software has been shown to reliably measure cardiac output (CO) in cardiac surgical patients. However, concerns have been raised regarding its accuracy in vasoplegic states. The aim of the present multicenter study was to investigate the accuracy of the third-generation software in patients with sepsis, particularly when total systemic vascular resistance (TSVR) is low. METHODS: Fifty-eight septic patients were included in this prospective observational study in four university-affiliated ICUs. Reference CO was measured by bolus pulmonary thermodilution (iCO) using 3-5 cold saline boluses. Simultaneously, CO was computed from the arterial pressure curve recorded on a computer using the second-generation (CO(G2)) and third-generation (CO(G3)) FloTrac software. CO was also measured by semi-continuous pulmonary thermodilution (CCO). RESULTS: A total of 401 simultaneous measurements of iCO, CO(G2), CO(G3), and CCO were recorded. The mean (95%CI) biases between CO(G2) and iCO, CO(G3) and iCO, and CCO and iCO were -10 (-15 to -5)% [-0.8 (-1.1 to -0.4) L/min], 0 (-4 to 4)% [0 (-0.3 to 0.3) L/min], and 9 (6-13)% [0.7 (0.5-1.0) L/min], respectively. The percentage errors were 29 (20-37)% for CO(G2), 30 (24-37)% for CO(G3), and 28 (22-34)% for CCO. The difference between iCO and CO(G2) was significantly correlated with TSVR (r(2) = 0.37, p < 0.0001). A very weak (r(2) = 0.05) relationship was also observed for the difference between iCO and CO(G3). CONCLUSIONS: In patients with sepsis, the third-generation FloTrac software is more accurate, as precise, and less influenced by TSVR than the second-generation software.

Present-day prehospital airway management in the former Eastern German state of Thuringia: equipment and education of emergency physicians.

We describe the condition of education and equipment regarding prehospital airway management in the German federal state of Thuringia, representing a part of former Eastern Germany. In 2006 a postal survey of the 39 emergency medical stations (EMS) in Thuringia was carried out. The response rate was 100%. In 72% of the EMS, a device for extraglottic airway management and in all EMS a device for cricothyrotomy was available. A device to monitor end-tidal CO2 was available in 41%. Difficulties in airway management in the past two years were reported from 74% of the EMS. Ongoing training and education in airway management is provided in 82% of the emergency districts. This survey reveals wide variations in the equipment for airway management available to prehospital emergency physicians in Thuringia. Given the reported difficulties in airway management, availability of a more standardized set of airway management devices in Thuringia may be helpful.

Students insert the laryngeal tube quicker and more often successful than the esophageal-tracheal combitube in a manikin.

BACKGROUND: Endotracheal intubation remains the standard of airway management. Because intubation skills are difficult to acquire, for medical students teaching of easier to learn techniques should be considered. METHODS: We retrospectively analyzed data that were collected in a University teaching facility. 264 medical students were taught how to use laryngeal tube (LT) and Esophageal Tracheal Combitube((R)) (ETC) in a manikin. The students underwent one of two different types of extraglottic airway management training consisting of either long lecture (30min) and intensive training (2h) (group IT, n=48), or brief (10min) lecture and 20min of training (group BT, n=216). Both groups underwent a test 6 weeks after training, group IT had an additional test 24h after training. RESULTS: After 24h students in group IT were faster using the LT than the ETC (31.7s+/-2.1 vs. 51.9s+/-5.8, p<0.001). Up to 6 weeks after training students were able to place the LT significantly faster than the ETC in both groups (26.5s+/-2.1 vs. 53.9s+/-5.8 group IT and 43.4s+/-1.6 vs. 103.8s+/-4.4 group BT, p<0.001). At 24h and 6 weeks following intensive training, there was no statistical difference in the time required for insertion of either device. CONCLUSION: Following different training scenarios in a manikin, students were able to place the LT much faster than the ETC. Even brief training was sufficient to generate short insertion times for the LT.

The level of cardiac output affects the relationship and agreement between pulmonary artery and transpulmonary aortic thermodilution measurements in an animal model.

OBJECTIVE: The authors investigated the relationship between pulmonary artery and transpulmonary aortic thermodilution cardiac output measurements under conditions of increasing cardiac output (CO). DESIGN: Animal study with repeated simultaneous measurements comparing 2 cardiac output measurement techniques. SETTING: Experimental animal facility of a university hospital. PARTICIPANTS: Ten female pigs. INTERVENTIONS: In anesthetized pigs, an aortic thermistor catheter and a pulmonary artery catheter (PAC) were inserted. Then dobutamine was infused under continuous cardiac output (CCO) monitoring to target different levels of CO. After each L/min increase of CCO simultaneous aortic and PAC thermodilution, CO measurements were performed by using a bolus injection of cooled normal saline and the amount of thermal indicator loss (TL) was calculated. MEASUREMENTS AND MAIN RESULTS: Pooled analysis of CO data with the method of Bland and Altman showed that aortic thermodilution CO was higher than PAC thermodilution CO with a bias of 3.8% +/- 11.1%. The range of TL was 30.4% to -10.1%. Differential analysis according to the range of CO revealed that, in each animal under conditions of low CO, aortic thermodilution CO was higher than PAC thermodilution CO, whereas results were inverse under conditions of high CO. CONCLUSIONS: The authors concluded that the amount of CO differentially affects the relationship between aortic and PAC thermodilution CO. TL and recirculation may be the explanation for this finding.

Measuring cardiac output in one-lung ventilation: a comparison of pulmonary artery and transpulmonary aortic measurements in pigs.

OBJECTIVE: The agreement between cardiac output measurements via pulmonary artery thermodilution (CO[PA]) and transpulmonary aortic thermodilution (CO[AT]) during one-lung ventilation was studied. DESIGN: Animal study with repeated simultaneous measurements comparing 2 cardiac output measurement techniques. SETTING: Experimental animal facility of a university department. PARTICIPANTS: Forty-eight female pigs (26-42 kg). INTERVENTIONS: The pigs were anesthetized, tracheally intubated, and mechanically ventilated. After placement of an aortic thermistor catheter via the femoral artery and a pulmonary artery catheter, a double-lumen tube was placed via tracheotomy. During one-lung ventilation in each animal, 3 measurements with pulmonary artery thermodilution and transpulmonary aortic thermodilution were performed in different hemodynamic states. Both thermistors were connected to 1 computer system, and 144 simultaneous cardiac output measurements were analyzed. MEASUREMENTS AND MAIN RESULTS: Linear regression analyses revealed a close relationship between the 2 methods: CO(AT) = 0.81 CO(PA) + 1.04 (L/min) (r = 0.96, p < 0.0001). Bland-Altman analysis showed that CO(AT) was slightly higher than the CO(PA) with a bias of 0.2 +/- 0.5 L/min. However, in higher CO states, an inversion of this relationship was found, possibly because of indicator loss and recirculation. CONCLUSIONS: The pulmonary artery thermodilution and the transpulmonary aortic thermodilution techniques both accurately measure cardiac output during one-lung ventilation.

Lung perfusion, shunt fraction, and oxygenation during one-lung ventilation in pigs: the effects of desflurane, isoflurane, and propofol.

OBJECTIVE: To study how desflurane, isoflurane, and propofol affect pulmonary perfusion, shunt fraction, and systemic oxygenation during one-lung ventilation (OLV) in vivo. DESIGN: Prospective animal study with a crossover design. SETTING: Animal laboratory of a university hospital. PARTICIPANTS: Twelve female pigs. INTERVENTIONS: The pigs were anesthetized, tracheally intubated, and mechanically ventilated. After placement of femoral arterial and thermodilution pulmonary artery catheters, a left-sided, double-lumen tube (DLT) was placed via tracheotomy. After DLT placement, F(I)O(2) was adjusted at 0.8, and anesthesia was continued in random order with 1 minimal alveolar concentration of desflurane, 1 minimal alveolar concentration of isoflurane, or propofol. MEASUREMENTS AND MAIN RESULTS: Measurements of respiratory and hemodynamic parameters were made after stabilization at each anesthetic. During OLV, perfusion of the nonventilated lung and shunt fraction were comparable during all 3 anesthetics. PaO(2) was lower during desflurane and isoflurane anesthesia as compared with propofol anesthesia. Mixed venous PO(2) and cardiac output were lower with desflurane and isoflurane as compared with propofol. CONCLUSIONS: In a clinically relevant model of OLV cardiac output, PaO(2) and mixed venous PO(2) decreased during desflurane and isoflurane as compared with propofol, whereas perfusion of the nonventilated lung and shunt fraction remained comparable.