Angiotensin II for the Treatment of Vasodilatory Shock.

BACKGROUND: Vasodilatory shock that does not respond to high-dose vasopressors is associated with high mortality. We investigated the effectiveness of angiotensin II for the treatment of patients with this condition. METHODS: We randomly assigned patients with vasodilatory shock who were receiving more than 0.2 µg of norepinephrine per kilogram of body weight per minute or the equivalent dose of another vasopressor to receive infusions of either angiotensin II or placebo. The primary end point was a response with respect to mean arterial pressure at hour 3 after the start of infusion, with response defined as an increase from baseline of at least 10 mm Hg or an increase to at least 75 mm Hg, without an increase in the dose of background vasopressors. RESULTS: A total of 344 patients were assigned to one of the two regimens; 321 received a study intervention (163 received angiotensin II, and 158 received placebo) and were included in the analysis. The primary end point was reached by more patients in the angiotensin II group (114 of 163 patients, 69.9%) than in the placebo group (37 of 158 patients, 23.4%) (odds ratio, 7.95; 95% confidence interval [CI], 4.76 to 13.3; P<0.001). At 48 hours, the mean improvement in the cardiovascular Sequential Organ Failure Assessment (SOFA) score (scores range from 0 to 4, with higher scores indicating more severe dysfunction) was greater in the angiotensin II group than in the placebo group (-1.75 vs. -1.28, P=0.01). Serious adverse events were reported in 60.7% of the patients in the angiotensin II group and in 67.1% in the placebo group. Death by day 28 occurred in 75 of 163 patients (46%) in the angiotensin II group and in 85 of 158 patients (54%) in the placebo group (hazard ratio, 0.78; 95% CI, 0.57 to 1.07; P=0.12). CONCLUSIONS: Angiotensin II effectively increased blood pressure in patients with vasodilatory shock that did not respond to high doses of conventional vasopressors. (Funded by La Jolla Pharmaceutical Company; ATHOS-3 ClinicalTrials.gov number, NCT02338843 .).

Early assessment of cardiac troponin I predicts the postoperative cardiac status and clinical course after congenital heart disease surgery.

Cardiac troponin I (cTnI) is a regulatory protein with a high sensitivity and specificity for cardiac injury. Preoperative and postoperative elevations of cTnI are usually considered predictors of the mortality and morbidity. However, little is known about the relationship between the cTnI and postoperative course after the congenital heart disease (CHD) operation. Sixty-five consecutive patients who underwent cardiac surgery for CHD at our institution between March 2016 and January 2017 were included. The cTnI was measured after the operation. Also, the association between the cTnI and duration of the catecholamine use, ICU stay, aortic cross clamp time, and other clinical parameters were assessed. The cTnI level on postoperative day 1 was positively correlated with the duration of the catecholamine use (p < 0.001) and ICU stay (p < 0.001). Also, a higher cTnI level was associated with a lower urine volume and higher lactate level 24 h after the ICU admission. In the multivariable regression analysis, the cTnI was a significant independent predictor of the catecholamine use (p = 0.002) and ICU stay (p = 0.003). The cTnI level on postoperative day 1 was a predictor of the duration of the catecholamine use and ICU stay.

Association between high dose catecholamine support and liver dysfunction following cardiac surgery.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass is a well-established procedure. However, up to 20% to 30% of patients require high dose vasopressor or inotropic support following surgery, enhancing the risk of organ dysfunction and impacting mortality. Nonalcoholic fatty liver disease (NAFLD) is a frequent finding in these patients and may be involved in the pathophysiology of vasoplegia and cardiac failure. METHODS: Retrospective analysis of 463 patients undergoing elective cardiac surgery in 2014 at our institution. NAFLD was defined using the NAFLD fibrosis score and the vasoactive-inotropy score was used to determine postoperative vasopressor and inotropic dependency. RESULTS: Patients with NAFLD more often presented with high vasopressor or inotropic support compared to patients without NAFLD, resulting in significant differences after 6 hours (n = 20 [27.0%] of 74 patients), 12 hours (n = 20 [27.0%] of 74 patients), and on the first postoperative day (n = 12 [16.4%] of 73 patients) of intensive care unit (ICU) treatment. Multivariate analysis revealed time of catecholamine application (P = .001), preoperative left ventricular ejection fraction (P = .001), type of surgery (P = .001), model of endstage liver disease on hospital admission (P = .002), pre-existing pulmonary hypertension (P = .004) and NAFLD-time interaction (P = .05) as independent predictors of high vasopressor and inotropic support. Patients with NAFLD had higher degrees of extrahepatic organ dysfunction, were more dependent on hemodialysis, spent more days in the ICU and within the hospital. Patients with NAFLD and high catecholamine support had the highest mortality rates among the study population. CONCLUSIONS: NAFLD is a common finding in elective cardiac surgery patients. Anesthesiologists and intensivists should be sensitive for the specific risk profile of this population.

Acute Catecholamine Exposure Causes Reversible Myocyte Injury Without Cardiac Regeneration.

RATIONALE: Catecholamines increase cardiac contractility, but exposure to high concentrations or prolonged exposures can cause cardiac injury. A recent study demonstrated that a single subcutaneous injection of isoproterenol (ISO; 200 mg/kg) in mice causes acute myocyte death (8%-10%) with complete cardiac repair within a month. Cardiac regeneration was via endogenous cKit(+) cardiac stem cell-mediated new myocyte formation. OBJECTIVE: Our goal was to validate this simple injury/regeneration system and use it to study the biology of newly forming adult cardiac myocytes. METHODS AND RESULTS: C57BL/6 mice (n=173) were treated with single injections of vehicle, 200 or 300 mg/kg ISO, or 2 daily doses of 200 mg/kg ISO for 6 days. Echocardiography revealed transiently increased systolic function and unaltered diastolic function 1 day after single ISO injection. Single ISO injections also caused membrane injury in ≈10% of myocytes, but few of these myocytes appeared to be necrotic. Circulating troponin I levels after ISO were elevated, further documenting myocyte damage. However, myocyte apoptosis was not increased after ISO injury. Heart weight to body weight ratio and fibrosis were also not altered 28 days after ISO injection. Single- or multiple-dose ISO injury was not associated with an increase in the percentage of 5-ethynyl-2'-deoxyuridine-labeled myocytes. Furthermore, ISO injections did not increase new myocytes in cKit(+/Cre)×R-GFP transgenic mice. CONCLUSIONS: A single dose of ISO causes injury in ≈10% of the cardiomyocytes. However, most of these myocytes seem to recover and do not elicit cKit(+) cardiac stem cell-derived myocyte regeneration.

Electronic Medication Regimen Complexity Index at admission and complications during hospitalization in medical wards: a tool to improve quality of care?

OBJECTIVE: Adverse events during hospitalization are a major worry considering their frequency and their burden. Many could be avoided by immediate identification of at-risk patients at admission and adapted prevention. The complexity of a patient's medication regimen immediately available at admission is a good indicator of the complexity of the patient's condition. This study aims to determine whether the electronic Medication Regimen Complexity Index (MRCI) at admission is associated with complications during hospitalization. DESIGN: We performed a multilevel logistic regression model, adjusted for age and sex. SETTING: Premier Perspective™ database, a clinical and financial information system from 417 US hospitals. PARTICIPANTS: Adults hospitalized for more than 3 days in a medical ward and included in Premier's Perspective™ database for 2006. INTERVENTION(S): Multilevel logistic regression. MAIN OUTCOME MEASURE: Association of the MRCI and complications during hospitalization, defined as in-hospital death, hospital-acquired infection, pressure ulcers; and need for highly technical healthcare, identified as the secondary introduction of catecholamines. RESULTS: In total, 1 592 383 admissions were included. The median MRCI at admission was 13 [interquartile range: 9-19]. The higher the MRCI, the higher the adjusted odds ratio of the following: in-hospital mortality, hospital-acquired infections, pressure ulcers and the secondary introduction of catecholamines. CONCLUSIONS: Our results suggested that the MRCI at admission was correlated with patient complexity, independent of age. Considering that patients with complex conditions pose a heavier workload for staff, measuring MRCI at admission could be used to allocate resources in medical wards at an institutional level. The MRCI might be a useful tool to assess the management of care.

Critical Care Skill Triad for Tactical Evacuations.

OBJECTIVE: Providing medical support to French soldiers deployed on war theater everywhere around the world is the first mission of the French Military Medical Service (FMMS). En-route critical care is critical to maintain the continuum of care and safety during forward and tactical medical evacuation (MEDEVAC). The FMMS has developed specific training programs to ensure optimal en-route critical care air transport. These courses need to be continuously adjusted to the returns of experience and to the operational changes. The aim of our survey was to characterize the critical care skills required for tactical MEDEVAC on fixed wing aircraft. METHODS: A 10-items survey was sent to 22 flight surgeons previously deployed in the Sahel-Saharan Strip. Eight questions focused on basic critical care skills. The 2 last items assessed the flight surgeons' willingness to follow a pre deployment course in a critical care unit and in a transfusion center. RESULTS: Fourteen of the 22 flight surgeons responded to the survey. All but one responder had to deal with at least one critical care skill. The most frequent critical care skills required were the management of mechanical ventilation, catecholamine infusion and blood product transfusion. Five of the 14 responders reported on-board blood product transfusion, including red blood cells, lyophilized plasma and fresh whole blood. CONCLUSION: Our survey highlights the need for the MEDEVAC teams to be skilled in critical care medicine. We defined a triad of critical care skills required for the management of severe casualties, including the management of mechanical ventilation, catecholamine infusion and blood product transfusion.

Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial.

Importance: Low cardiac output syndrome after cardiac surgery is associated with high morbidity and mortality in patients with impaired left ventricular function. Objective: To assess the ability of preoperative levosimendan to prevent postoperative low cardiac output syndrome. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled trial conducted in 13 French cardiac surgical centers. Patients with a left ventricular ejection fraction less than or equal to 40% and scheduled for isolated or combined coronary artery bypass grafting with cardiopulmonary bypass were enrolled from June 2013 until May 2015 and followed during 6 months (last follow-up, November 30, 2015). Interventions: Patients were assigned to a 24-hour infusion of levosimendan 0.1 µg/kg/min (n = 167) or placebo (n = 168) initiated after anesthetic induction. Main Outcomes and Measures: Composite end point reflecting low cardiac output syndrome with need for a catecholamine infusion 48 hours after study drug initiation, need for a left ventricular mechanical assist device or failure to wean from it at 96 hours after study drug initiation when the device was inserted preoperatively, or need for renal replacement therapy at any time postoperatively. It was hypothesized that levosimendan would reduce the incidence of this composite end point by 15% in comparison with placebo. Results: Among 336 randomized patients (mean age, 68 years; 16% women), 333 completed the trial. The primary end point occurred in 87 patients (52%) in the levosimendan group and 101 patients (61%) in the placebo group (absolute risk difference taking into account center effect, -7% [95% CI, -17% to 3%]; P = .15). Predefined subgroup analyses found no interaction with ejection fraction less than 30%, type of surgery, and preoperative use of ß-blockers, intra-aortic balloon pump, or catecholamines. The prevalence of hypotension (57% vs 48%), atrial fibrillation (50% vs 40%), and other adverse events did not significantly differ between levosimendan and placebo. Conclusions and Relevance: Among patients with low ejection fraction who were undergoing coronary artery bypass grafting with cardiopulmonary bypass, levosimendan compared with placebo did not result in a significant difference in the composite end point of prolonged catecholamine infusion, use of left ventricular mechanical assist device, or renal replacement therapy. These findings do not support the use of levosimendan for this indication. Trial Registration: EudraCT Number: 2012-000232-25; clinicaltrials.gov Identifier: NCT02184819.

Early High-Volume Hemofiltration versus Standard Care for Post-Cardiac Surgery Shock. The HEROICS Study.

RATIONALE: Post-cardiac surgery shock is associated with high morbidity and mortality. By removing toxins and proinflammatory mediators and correcting metabolic acidosis, high-volume hemofiltration (HVHF) might halt the vicious circle leading to death by improving myocardial performance and reducing vasopressor dependence. OBJECTIVES: To determine whether early HVHF decreases all-cause mortality 30 days after randomization. METHODS: This prospective, multicenter randomized controlled trial included patients with severe shock requiring high-dose catecholamines 3-24 hours post-cardiac surgery who were randomized to early HVHF (80 ml/kg/h for 48 h), followed by standard-volume continuous venovenous hemodiafiltration (CVVHDF) until resolution of shock and recovery of renal function, or conservative standard care, with delayed CVVHDF only for persistent, severe acute kidney injury. MEASUREMENTS AND MAIN RESULTS: On Day 30, 40 of 112 (36%) HVHF and 40 of 112 (36%) control subjects (odds ratio, 1.00; 95% confidence interval, 0.64-1.56; P = 1.00) had died; only 57% of the control subjects had received renal-replacement therapy. Between-group survivors' Day-60, Day-90, intensive care unit, and in-hospital mortality rates, Day-30 ventilator-free days, and renal function recovery were comparable. HVHF patients experienced faster correction of metabolic acidosis and tended to be more rapidly weaned off catecholamines but had more frequent hypophosphatemia, metabolic alkalosis, and thrombocytopenia. CONCLUSIONS: For patients with post-cardiac surgery shock requiring high-dose catecholamines, the early HVHF onset for 48 hours, followed by standard volume until resolution of shock and recovery of renal function, did not lower Day-30 mortality and did not impact other important patient-centered outcomes compared with a conservative strategy with delayed CVVHDF initiation only for patients with persistent, severe acute kidney injury. Clinical trial registered with www.clinicaltrials.gov (NCT 01077349).

Functional brown adipose tissue limits cardiomyocyte injury and adverse remodeling in catecholamine-induced cardiomyopathy.

Brown adipose tissue (BAT) has well recognized thermogenic properties mediated by uncoupling protein 1 (UCP1); more recently, BAT has been demonstrated to modulate cardiovascular risk factors. To investigate whether BAT also affects myocardial injury and remodeling, UCP1-deficient (UCP1(-/-)) mice, which have dysfunctional BAT, were subjected to catecholamine-induced cardiomyopathy. At baseline, there were no differences in echocardiographic parameters, plasma cardiac troponin I (cTnI) or myocardial fibrosis between wild-type (WT) and UCP1(-/-) mice. Isoproterenol infusion increased cTnI and myocardial fibrosis and induced left ventricular (LV) hypertrophy in both WT and UCP1(-/-) mice. UCP1(-/-) mice also demonstrated exaggerated myocardial injury, fibrosis, and adverse remodeling, as well as decreased survival. Transplantation of WT BAT to UCP1(-/-) mice prevented the isoproterenol-induced cTnI increase and improved survival, whereas UCP1(-/-) BAT transplanted to either UCP1(-/-) or WT mice had no effect on cTnI release. After 3 days of isoproterenol treatment, phosphorylated AKT and ERK were lower in the LV's of UCP1(-/-) mice than in those of WT mice. Activation of BAT was also noted in a model of chronic ischemic cardiomyopathy, and was correlated to LV dysfunction. Deficiency in UCP1, and accompanying BAT dysfunction, increases cardiomyocyte injury and adverse LV remodeling, and decreases survival in a mouse model of catecholamine-induced cardiomyopathy. Myocardial injury and decreased survival are rescued by transplantation of functional BAT to UCP1(-/-) mice, suggesting a systemic cardioprotective role of functional BAT. BAT is also activated in chronic ischemic cardiomyopathy.

Low-dose corticosteroid use and mortality in severe community-acquired pneumonia patients.

The relationship between low-dose corticosteroid use and mortality in patients with severe community-acquired pneumonia (CAP) remains unclear. 6925 patients with severe CAP who received mechanical ventilation with or without shock (defined as use of catecholamines) at 983 hospitals were identified using a Japanese nationwide administrative database. The main outcome measure was 28-day mortality. 2524 patients with severe CAP who received catecholamines were divided into corticosteroid (n=631) and control (n=1893) groups. The 28-day mortality was significantly different between corticosteroid and control groups (unmatched: 24.6% versus 36.3%, p<0.001; propensity score-matched: 25.3% versus 32.6%, p=0.01; inverse probability-weighted: 27.5% versus 34.2%, p<0.001). 4401 patients with severe CAP who did not receive catecholamines were also divided into corticosteroid (n=1112) and control (n=3289) groups. The 28-day mortality was not significantly different between corticosteroid and control groups in propensity score-matched analyses (unmatched: 16.0% versus 19.4%, p=0.01; propensity score-matched: 17.7% versus 15.6%, p=0.22; inverse probability-weighted: 18.8% versus 18.2%, p=0.44). Low-dose corticosteroid use may be associated with reduced 28-day mortality in patients with septic shock complicating CAP.

Low predictability of three different noninvasive methods to determine fluid responsiveness in critically ill children.

OBJECTIVE: To predict fluid responsiveness by noninvasive methods in a pediatric critical care population. DESIGN: Prospective observational clinical trial. SETTING: PICU in a tertiary care academic hospital. PATIENTS: Thirty-one pediatric patients aged from 1 day to 13 years under mechanical ventilation and on catecholamine support. INTERVENTIONS: We tested three noninvasive methods to predict fluid responsiveness: an esophageal Doppler system (CardioQ), a pulse contour analysis algorithm system (LiDCOrapid), and respiratory variations in vena cava inferior diameter. Stroke volume index was measured by transthoracic echocardiography before and after fluid challenge to determine fluid responders. Infusion of 10 mL/kg hydroxyethylstarch 130/0.4. MEASUREMENTS AND MAIN RESULTS: Predictability of fluid responsiveness was only found in Doppler peak velocity of descending aortal blood flow. Increased peak velocity with reduction after fluid bolus was predictive for nonresponding to IV fluid challenge. Sensitivity and specificity of peak velocity were 69% and 73%, respectively. The cut point was set at 135.5 cm/s. The lower the Doppler peak velocity, the higher was the probability for a fluid response. Neither stroke volume variations nor respiratory variations in vena cava inferior diameter during mechanical ventilation were useful in predicting fluid responsiveness in this pediatric patient population. None of the children had abdominal hypertension measured by bladder pressure. CONCLUSIONS: Dynamic preload variables such as stroke volume variation or respiratory variations in vena cava inferior diameter may not be useful for predicting fluid responsiveness in certain pediatric patient populations. Esophageal Doppler peak velocity was predictive of fluid responsiveness where a target value of more than 135,5 cm/s may be a signal to terminate further fluid challenges. This target value may be different in different age groups, as esophageal Doppler peak velocity varies with age.

[Treatment of acute heart failure]. / Therapie der akuten Herzinsuffizienz.

Acute heart failure is a symptom complex of heterogeneous etiology. Clinically, it comprises a broad spectrum ranging from hypertensive pulmonary edema in patients with preserved left ventricular systolic function up to cardiogenic shock in patients with severely depressed left ventricular function. The pathophysiology of acute heart failure is based on a mismatch between myocardial pump function and afterload. Besides causal measures, vasodilators and diuretics are the mainstay of therapy. Catecholamines are indicated only when other drugs are unsuccessful. Opioids are often used in clinical practice but should be used cautiously as they are associated with a negative prognosis. Further adjunctive treatment consists of thromboembolism prophylaxis, non-invasive ventilation and in some cases mechanical circulatory support and renal replacement therapy. This article discusses the differential use of these treatment modalities.

Hypotension following patent ductus arteriosus ligation: the role of adrenal hormones.

OBJECTIVE: To test the hypothesis that an impaired adrenal response to stress might play a role in the hypotension that follows patent ductus arteriosus (PDA) ligation. STUDY DESIGN: We performed a multicenter study of infants born at <32 weeks' gestation who were about to undergo PDA ligation. Serum adrenal steroids were measured 3 times: before and after a cosyntropin (1.0 µg/kg) stimulation test (performed before the ligation), and at 10-12 hours after the ligation. A standardized approach for diagnosis and treatment of postoperative hypotension was followed at each site. A modified inotrope score (1 × dopamine [µg/kg/min] + 1 × dobutamine) was used to monitor the catecholamine support an infant received. Infants were considered to have catecholamine-resistant hypotension if their greatest inotrope score was >15. RESULTS: Of 95 infants enrolled, 43 (45%) developed hypotension and 14 (15%) developed catecholamine-resistant hypotension. Low postoperative cortisol levels were not associated with the overall incidence of hypotension after ligation. However, low cortisol levels were associated with the refractoriness of the hypotension to catecholamine treatment. In a multivariate analysis: the OR for developing catecholamine-resistant hypotension was OR 36.6, 95% CI 2.8-476, P = .006. Low cortisol levels (in infants with catecholamine-resistant hypotension) were not attributable to adrenal immaturity or impairment; their cortisol precursor concentrations were either low or unchanged, and their response to cosyntropin was similar to infants without catecholamine-resistant hypotension. CONCLUSION: Infants with low cortisol concentrations after PDA ligation are likely to develop postoperative catecholamine-resistant hypotension. We speculate that decreased adrenal stimulation, rather than an impaired adrenal response to stimulation, may account for the decreased production.

Impact of catecholamines in cardiac arrest due to acute asphyxia--a study in piglets.

BACKGROUND: Early intravenous epinephrine administration may help to achieve return of spontaneous circulation in cardiac arrest (CA). However, venous access can be challenging in small children. This study investigates the effect of intravenous and intramuscular epinephrine in treatment of asphyxial CA. METHODS: Twenty-eight, 2-5-weeks-old, anesthetized piglets were asphyxiated by ventilation withdrawal. CA was untreated for 8 min, followed by 2 min of basic life support. Following this, epinephrine iv (10 µg·kg(-1) , group IV), epinephrine im (100 µg·kg(-1) , group IM), or normal saline (group NS) were administered. Further doses of epinephrine were given in group IV every 4 min, in group IM after 10 min if required. After twenty-two minutes of CA, iv epinephrine was given to all animals still in CA. Outcome measures were survival and epinephrine plasma concentrations. RESULTS: Ten animals regained spontaneous circulation after 2 min of basic life support. Therefore, no drug treatment was administered (drop out). Resuscitation was effective in 2 pigs of group IM (n = 6), in 6 of group NS (n = 8) and in all of group IV (n = 4). Nonsurvivors had higher epinephrine (P < 0.01) and norepinephrine (P < 0.01) plasma concentrations prior to start of resuscitation. Median increase in epinephrine plasma concentration from T0 to T5 was 138, 134, and 29 nm in group IV, IM, and NS, respectively. CONCLUSIONS: Intravenous and intramuscular administered epinephrine led to similar increase in plasma concentrations during resuscitation of asphyxial CA without hemodynamic or survival benefit. High endogenous epinephrine and norepinephrine plasma concentrations were negative predictors for survival.

[Anesthetic management of a hemodialysis patient presenting with apparent LV diastolic dysfunction after undergoing extensive pericardiectomy for constrictive pericarditis].

We present a case of anesthetic management in a hemodialysis patient suffering from constrictive pericarditis who underwent pericardiectomy. The patient was a 54-year-old male, complicated with hypertension, diabetes and coronary artery disease, with congestive heart disease of NYHA III. After anesthetic induction with midazolam and fentanyl, pericardiectomy was performed with CPB stand by for unexpected surgical blood loss. Transesophageal echocardiography (TEE) revealed severely constricted ventricles with normal ejection fraction. CPB was induced due to refractory ventricular fibrillation during pericardiectomy. CPB was discontinued after performing pericardiectomy and CABG, and cardiac index increased from 1.3 to 3.0 l x min(-1) x m(-2) and stroke index increased from 18.6 to 34.1 ml x beats(-1) x m(-2). However, continuous catecholamine infusion including adrenaline and noradrenaline and intraaortic balloon pumping were necessary to maintain systemic blood pressure against systemic hypotension with pulmonary hypertension, regardless of normal cardiac index. TEE after pericardiectomy revealed a dilated right ventricle and unchanged size of the left ventricle compared with those at pre-operative exam. The patient remained in an intensive care for 9 days and was discharged on the 21st post-operative day. NYHA status improved from III to II after the surgery. Post-operative echocardiography revealed dilated left atrium and apparent diastolic dysfunction with normal ejection fraction compared with those in the pre-operative period.

[Anesthetic management of patients with dilated cardiomyopathy undergoing non-cardiac surgery].

There is little information on the perioperative management of patients with dilated cardiomyopathy (DCM) undergoing non-cardiac surgery. The presence of a history or signs of heart failure and un-diagnosed DCM preoperatively, may be associated with an increased risk during non-cardiac surgery. In these patients, preoperative assessment of LV function, including echocardiography, and assessment of an individual's capacity to perform a spectrum of common daily tasks may be recommended to quantify the severity of systolic function. It is important to prevent low cardiac output and arrhythmia for the perioperative management of patients with DCM. Sympathetic hyperactivity often causes atrial or ventricular tachyarrhythmia, which could worsen systemic hemodynamics in these patients. In particular, the prevention of life-threatening arrhythmia, such as, ventricular tachycardia or ventricular fibrillation is important. To prevent perioperative low output syndrome, inotropic support, using catecholamines or phosphodiesterase inhibitors with or without vasodilators should be performed under careful monitoring. It is desirable to use a pulmonary-artery catheter during moderate to high risk surgery, because the optimum level of left ventricular pre-load is very narrow in these patients. Every effort must be made to detect postoperative heart failure by careful monitoring, including PAC, and physical examination.

Association between plasma cyclic guanosine monophosphate levels and hemodynamic instability during liver transplantation.

The activation of cyclic guanosine monophosphate (cGMP) production in patients with end-stage liver disease (ESLD) has been associated with hemodynamic instability during orthotopic liver transplantation (OLT). The aim of this prospective, observational study was to investigate the involvement of cGMP in the mediation of profound hypotension during liver graft reperfusion. An additional objective was to determine whether preoperative cGMP levels are associated with intraoperative hemodynamic instability. Forty-four consecutive patients undergoing OLT were included in the study. Blood samples for cGMP analysis were obtained from (1) the radial artery before the surgical incision; (2) the radial artery, portal vein, and flush blood during the anhepatic phase; and (3) the radial artery 20 minutes after liver graft reperfusion. On the basis of a statistical analysis, the patients were divided into 2 groups: group 1 (preoperative cGMP level ≥ 0.05 µmol/L) and group 2 (preoperative cGMP level < 0.05 µmol/L). We demonstrated a significant correlation between the preoperative levels of cGMP and the amount of catecholamine required to maintain hemodynamic stability during reperfusion (r = 0.52, P < 0.001), the length of the hospital stay (r = 0.38, P = 0.01), and the length of the intensive care unit (ICU) stay (r = 0.44, P = 0.004). We also demonstrated a significantly higher intraoperative catecholamine requirement (P < 0.001) and a prolonged postoperative ICU stay (P = 0.02) in group 1 patients versus group 2 patients. In conclusion, this study demonstrates increased baseline cGMP production in patients with ESLD, which is significantly associated with severe hypotension during OLT. We suggest that preoperative levels of cGMP correlate with hemodynamic instability during liver graft reperfusion.

Influence of prehospital volume replacement on outcome in polytraumatized children.

INTRODUCTION: Severe bleeding after trauma frequently results in poor outcomes in children. Prehospital fluid replacement therapy is regarded as an important primary treatment option. Our study aimed, through a retrospective analysis of matched pairs, to assess the influence of prehospital fluid replacement therapy on the post-traumatic course of severely injured children. METHODS: The data for 67,782 patients from the TraumaRegister DGU® of the German Trauma Society were analyzed. The following inclusion criteria were applied: injury severity score ≥16 points, primary admission, age 1 to 15 years old, systolic blood pressure ≥20 mmHg at the accident site and transfusion of at least one unit of packed red blood cells (pRBC) in the emergency trauma room prior to intensive care admission. As volume replacement therapy depends on age and body weight, especially in children, three subgroups were formed according to the mean value of the administered prehospital volume. The children were matched and enrolled into two groups according to the following criteria: intubation at the accident site (yes/no), Abbreviated Injury Scale (four body regions), accident year, systolic blood pressure and age group. RESULTS: A total of 31 patients in each group met the inclusion criteria. An increase in volume replacement was associated with an elevated need for a transfusion (≥10 pRBC: low volume, 9.7%; high volume, 25.8%; P = 0.18) and a reduction in the ability to coagulate (prothrombin time ratio: low volume, 58.7%; high volume, 55.6%; P = 0.23; prothrombin time: low volume, 42.2 seconds; high volume, 50.1 seconds; P = 0.38). With increasing volume, the mortality (low volume, 19.4%; high volume, 25.8%; P = 0.75) and multiple organ failure rates (group 1, 36.7%; group 2, 41.4%; P = 0.79) increased. With increased volume, the rescue time also increased (low volume, 62 minutes; high volume, 71.5 minutes; P = 0.21). CONCLUSION: For the first time, a tendency was shown that excessive prehospital fluid replacement in children leads to a worse clinical course with higher mortality and that excessive fluid replacement has a negative influence on the ability to coagulate.

[Investigation of the outcomes and complications in right thoracotomy approach for mitral valve reoperation].

BACKGROUND: Right thoracotomy is an alternative surgical technique for mitral valve reoperation. The purpose of this study is to determine whether right thoracotomy for mitral valve reoperation affects its perioperative outcomes and complications. METHODS: We investigated the perioperative events in consecutive mitral valve reoperations between January 2006 and November 2009. Demographic, intraoperative and postoperative data were collected and analyzed retrospectively. RESULTS: Five right thoracotomy cases and 22 repeated sternotomy cases were included. Thoracotomy group needed more platelet transfusion (median, 20 units in thoracotomy; 10 units in sternotomy; P=0.047). We had a higher frequency of adrenaline administration (60% in thoracotomy; 4.6% in sternotomy; P=0.005) and needed more doses of dobutamine in thoracotomy group (median, 16.0 microg x kg(-1) x min(-1) in thoracotomy ; 7.5 microg x kg(-1) x min(-1) in sternotomy; P=0.037) to wean them from cardiopulmonary bypass. Right thoracotomy did not reduce cardiopulmonary bypass time (median, 265 min in thoracotomy ; 199 min in sternotomy; P=0.126). We experienced two serious complications requiring reoperation in thoracotomy group, but diagnosed them with intraoperative transesophageal echocardiography. CONCLUSIONS: When we choose right thoracotomy for mitral valve reoperation, we should prepare more blood products and inotropic agents and should evaluate cardiac function by using intraoperative transesophageal echocardiography.

Vasopressin versus norepinephrine infusion in patients with septic shock.

BACKGROUND: Vasopressin is commonly used as an adjunct to catecholamines to support blood pressure in refractory septic shock, but its effect on mortality is unknown. We hypothesized that low-dose vasopressin as compared with norepinephrine would decrease mortality among patients with septic shock who were being treated with conventional (catecholamine) vasopressors. METHODS: In this multicenter, randomized, double-blind trial, we assigned patients who had septic shock and were receiving a minimum of 5 microg of norepinephrine per minute to receive either low-dose vasopressin (0.01 to 0.03 U per minute) or norepinephrine (5 to 15 microg per minute) in addition to open-label vasopressors. All vasopressor infusions were titrated and tapered according to protocols to maintain a target blood pressure. The primary end point was the mortality rate 28 days after the start of infusions. RESULTS: A total of 778 patients underwent randomization, were infused with the study drug (396 patients received vasopressin, and 382 norepinephrine), and were included in the analysis. There was no significant difference between the vasopressin and norepinephrine groups in the 28-day mortality rate (35.4% and 39.3%, respectively; P=0.26) or in 90-day mortality (43.9% and 49.6%, respectively; P=0.11). There were no significant differences in the overall rates of serious adverse events (10.3% and 10.5%, respectively; P=1.00). In the prospectively defined stratum of less severe septic shock, the mortality rate was lower in the vasopressin group than in the norepinephrine group at 28 days (26.5% vs. 35.7%, P=0.05); in the stratum of more severe septic shock, there was no significant difference in 28-day mortality (44.0% and 42.5%, respectively; P=0.76). A test for heterogeneity between these two study strata was not significant (P=0.10). CONCLUSIONS: Low-dose vasopressin did not reduce mortality rates as compared with norepinephrine among patients with septic shock who were treated with catecholamine vasopressors. (Current Controlled Trials number, ISRCTN94845869 [controlled-trials.com].).