Vasopressin in Cardiac Surgery: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To summarize the results of randomized controlled trials on the use of vasopressin as a vasopressor agent in cardiac surgery. DESIGN: Meta-analysis. PARTICIPANTS: Six-hundred-twenty-five adult patients undergoing elective or emergency cardiac surgery. INTERVENTIONS: Arginine vasopressin infusion (n = 313) or control/standard therapy (n = 312). MEASUREMENTS AND MAIN RESULTS: The rates of perioperative complications and postoperative mortality were used as primary and secondary endpoints, respectively. Fixed and/or random effects models were used to compare pooled odds ratios. Arginine vasopressin reduced the pooled odds ratio (OR) of perioperative complications (OR, 0.33; 95% confidence interval [CI], 0.2-0.54; p < 0.0001). A sensitivity analysis excluding the largest trial showed an unchanged reduction in perioperative complications (OR, 0.35; 95% CI, 0.18-0.69; p = 0.002). When analyzing each perioperative complication separately, vasopressin reduced the pooled OR of vasodilatory shock (OR, 0.4; 95% CI, 0.16-0.97; p = 0.04) and new-onset atrial fibrillation (OR, 0.42; 95% CI, 0.21-0.82; p = 0.01). The pooled OR of postoperative death was not different between patients treated with arginine vasopressin and those receiving standard therapy or placebo (OR, 0.83; 95% CI, 0.45-1.53; p = 0.55). The funnel plot for the primary endpoint suggested a relevant publication bias. All included trials suffered from a high risk of bias. CONCLUSION: Our meta-analysis suggests that arginine vasopressin may reduce the rate of perioperative complications in patients undergoing elective or emergency cardiac surgery. No difference in postoperative mortality was observed. An adequately powered multicenter trial is required for reliable estimation of the effects of arginine vasopressin on perioperative complication rates and mortality in cardiac surgical patients.

Histologic pathologies of the myocardium in septic shock: a prospective observational study.

Myocardial depression in septic shock is well known, but its pathophysiological genesis is incompletely understood. To assess the incidence and extent of stress-induced histologic myocardial alterations in septic shock, a prospective, observational, combined clinical and postmortem study was conducted, and 20 patients dying from septic shock were included. Exclusion criteria were younger than 18 years, pregnancy, open heart surgery or cardiopulmonary resuscitation, acute neurologic diseases, pheochromocytoma, and forensic autopsy. A systematic macropathologic evaluation was performed. Nine predefined heart sections were histologically screened for myocytolysis, interstitial fibrosis, contraction band necrosis, mononuclear infiltrates, interstitial edema, and tissue hemorrhage. Stress-induced pathologies were found in 90% to 100% of patients in all heart sections (myocytolysis, 100%; interstitial fibrosis, 100%; contraction band necrosis, 95%; mononuclear infiltrates, 90%; interstitial edema, 90%; tissue hemorrhage, 30%). The incidence and extent of contraction band necrosis, mononuclear infiltrates, and myocytolysis did not differ between sexes; patients with or without chronic ß-blocker, calcium antagonist, and/or statin premedication; or between the binary use of different catecholamine agents (all comparisons P > 0.05). The maximum epinephrine dose correlated with the overall extent of mononuclear infiltrates (Spearman-Rho, r = 0.704; P = 0.05) and myocytolysis (Spearman-Rho, r = 0.933; P = 0.001). Maximum norepinephrine doses correlated with the extent of mononuclear infiltrates in the left ventricular anterior wall (Spearman-Rho, r = 0.519; P = 0.02). The total duration of catecholamine therapy was correlated with the extent of mononuclear infiltrates in the apex (Spearman-Rho, r = 0.571; P = 0.009) and right atrium (Spearman-Rho, r = 0.535; P = 0.02). In conclusion, our results suggest that histologic lesions potentially indicative of stress-induced cardiotoxicity can be observed in most patients dying from septic shock.

The relationship between extravascular lung water and oxygenation in three patients with influenza A (H1N1)-induced respiratory failure.

This case series reports the correlation between extravascular lung water (EVLW) and the partial arterial oxygen pressure/fractional inspiratory oxygen (PaO(2)/FiO(2)) ratio in three patients with severe influenza A (H1N1)-induced respiratory failure. All patients suffered from grave hypoxia (PaO(2), 26-42 mmHg) and were mechanically ventilated using biphasic airway pressure (PEEP, 12-15 mmHg; FiO(2), 0.8-1) in combination with prone positioning at 12 hourly intervals. All patients were monitored using the PICCO system for 8-11 days. During mechanical ventilation, a total of 62 simultaneous determinations of the PaO(2)/FiO(2) ratio and EVLW were performed. A significant correlation between EVLW and the PaO(2)/FiO(2) ratio (Spearman-rho correlation coefficient, -0.852; p < 0.001) was observed. In all patients, a decrease in EVLW was accompanied by an improvement in oxygenation. Serum lactate dehydrogenase levels were elevated in all patients and significantly correlated with EVLW during the intensive care unit stay (Spearman-rho correlation coefficient, 0.786; p < 0.001). In conclusion, EVLW seems increased in patients with severe H1N1-induced respiratory failure and appears to be closely correlated with impairments of oxygenatory function.

Early fish oil supplementation and organ failure in patients with septic shock from abdominal infections: a propensity-matched cohort study.

BACKGROUND: Fish oil (FO) has immunomodulating effects and may improve organ function and outcome in critically ill patients. This retrospective, propensity-matched cohort study investigates the effects of early intravenous FO supplementation on organ failure in patients with septic shock from abdominal infection. METHODS: A medical database was retrospectively searched for critically ill patients admitted because of septic shock from abdominal infection (n = 194). Demographic, clinical, and laboratory data; FO supplementation (10 g/d) (n = 42); rate, degree, and number of organ failures assessed by the Sequential Organ Failure Assessment (SOFA) score; and secondary outcome variables were recorded. A propensity score-based model was used to establish 2 comparable groups (FO, n = 29; control, n = 29). Mann-Whitney rank sum test, Fisher exact test, and logistic regression analyses were used to compare variables between groups. RESULTS: There were no differences in the rate of single organ failures, the maximum SOFA score (median [interquartile range (IQR)], 12 [8-15] vs 11 [9-14]; P = .99), or the number of organ failures (median [IQR], 2 [1-3] vs 2 [1-3]; P = .54] between patients receiving FO supplementation and those not receiving supplementation. There were no group differences in the maximum C-reactive protein levels (P = .1), duration of mechanical ventilation (P = .65) or hemofiltration (P = .21), intensive care unit-acquired infections, intensive care unit length of stay (P = .59), and intensive care unit (P = 1) or hospital mortality (P = 1). CONCLUSIONS: Early intravenous FO may not decrease the number and degree of organ failures in patients with septic shock from abdominal infection. Future trials are needed before FO supplementation in septic shock from abdominal infection can be recommended.

Does standardization of critical care work?

PURPOSE OF REVIEW: This article discusses how standardization of intensive care work may decrease morbidity and mortality in the intensive care unit (ICU) by reducing practice variation and improving the overall quality of care. In this context, standardization should not only apply to the specific medical management of certain high-volume ICU diagnoses but should also be established for daily ICU procedures and information transmission during ward rounds and at the interface of interdisciplinary work. RECENT FINDINGS: Standardized procedures for placement of central venous catheters, implementation of strict hand hygiene and treatment of specific high volume ICU diagnoses using protocol-guided treatment algorithms or treatment bundles have convincingly demonstrated to decrease patient morbidity and mortality and healthcare expenditures. Standardization processes to improve patient-centered communication in the ICU are still in their early stages. SUMMARY: Standardization of most aspects of intensive care medicine has an enormous potential to improve patient care and outcome, reduce ICU/hospital length of stay as well as healthcare expenditures. Despite promising results from large studies standards known to improve patient outcome have not yet been widely implemented.

The association between body-mass index and patient outcome in septic shock: a retrospective cohort study.

BACKGROUND: It is unknown whether body-mass index (BMI) and commonly defined BMI categories are associated with mortality in patients with septic shock. METHODS: The database of a multidisciplinary intensive care unit (ICU) was retrospectively screened for adult patients with septic shock. BMI, demographic, clinical and laboratory variables together with outcome measures were collected in all patients. Subjects were categorized as follows: underweight, BMI < 18.5; normal weight, BMI 18.5-24.9; overweight, BMI 25-29.9; obesity, BMI >or= 30. Bivariate and multivariate logistic regression models were used to evaluate the association between BMI and outcome parameters. RESULTS: In total, 301 patients with septic shock were identified. BMI was bivariately associated with ICU mortality (OR 0.91; 95% CI 0.86-0.98; P = 0.007). There was no significant association between BMI and ICU mortality in the multivariate model but an increasing BMI tended to be associated with lower ICU mortality (OR 0.93; 95% CI 0.86-1.01; P = 0.09). Although overweight (OR 0.43; 95% CI 0.19-0.98; P = 0.04) and obese (OR 0.28; 95% CI 0.08-0.93; P = 0.04) patients had an independently lower risk of ICU death than those with normal weight, there was no difference in the risk of ICU death between normal weight and underweight patients (P = 0.22). A high BMI was independently associated with a lower frequency of acute delirium (P = 0.04) and a lower need for ICU re-admission (P = 0.001) but with a higher rate of ICU-acquired urinary tract infections (P = 0.02). CONCLUSIONS: BMI up to 50 does not appear to be associated with worse ICU and hospital mortality in patients with septic shock. In contrast, a high BMI may reduce the risk of death from septic shock.

How to protect the heart in septic shock: a hypothesis on the pathophysiology and treatment of septic heart failure.

Heart failure is a well-recognized manifestation of organ failure in sepsis and septic shock. The pathophysiology of septic heart failure is complex and currently believed to involve several mechanisms. So far, the contributory role of high plasma catecholamine levels has not been investigated. In this manuscript, we present a hypothesis suggesting that excessive catecholamine production and exogenous administration of catecholamines may relevantly contribute to the development of heart failure and cardiovascular collapse in patients suffering from septic shock. Substantially elevated plasma catecholamine levels were measured during critical illness and sepsis or septic shock. There is a growing body of clinical and experimental evidence demonstrating that high catecholamine plasma levels exert direct toxic effects on the heart. The pathophysiologic mechanisms involved in catecholamine-induced cardiomyocyte toxicity may involve a combination of inflammation, oxidative stress, and abnormal calcium handling resulting in myocardial stunning, apoptosis and necrosis. Clinical signs of catecholamine-induced heart failure can present with a wide range of symptoms reaching from subtle histological changes with preserved myocardial pump function to severe heart failure exhibiting a distinctive echocardiographic pattern which became known as "Takotsubo"-like cardiomyopathy or the left ventricular apical ballooning syndrome. In a medical intensive care unit patient population, presence of sepsis was the only variable associated with the development of left ventricular apical ballooning. Since several therapeutic interventions influence catecholamine plasma levels in septic shock patients, treatment strategies aiming at the reduction of endogenous or exogenous catecholamine exposure may protect the heart during septic shock and could facilitate patient survival.

Sympathetic overstimulation during critical illness: adverse effects of adrenergic stress.

The term ''adrenergic'' originates from ''adrenaline'' and describes hormones or drugs whose effects are similar to those of epinephrine. Adrenergic stress is mediated by stimulation of adrenergic receptors and activation of post-receptor pathways. Critical illness is a potent stimulus of the sympathetic nervous system. It is undisputable that the adrenergic-driven ''fight-flight response'' is a physiologically meaningful reaction allowing humans to survive during evolution. However, in critical illness an overshooting stimulation of the sympathetic nervous system may well exceed in time and scope its beneficial effects. Comparable to the overwhelming immune response during sepsis, adrenergic stress in critical illness may get out of control and cause adverse effects. Several organ systems may be affected. The heart seems to be most susceptible to sympathetic overstimulation. Detrimental effects include impaired diastolic function, tachycardia and tachyarrhythmia, myocardial ischemia, stunning, apoptosis and necrosis. Adverse catecholamine effects have been observed in other organs such as the lungs (pulmonary edema, elevated pulmonary arterial pressures), the coagulation (hypercoagulability, thrombus formation), gastrointestinal (hypoperfusion, inhibition of peristalsis), endocrinologic (decreased prolactin, thyroid and growth hormone secretion) and immune systems (immunomodulation, stimulation of bacterial growth), and metabolism (increase in cell energy expenditure, hyperglycemia, catabolism, lipolysis, hyperlactatemia, electrolyte changes), bone marrow (anemia), and skeletal muscles (apoptosis). Potential therapeutic options to reduce excessive adrenergic stress comprise temperature and heart rate control, adequate use of sedative/analgesic drugs, and aiming for reasonable cardiovascular targets, adequate fluid therapy, use of levosimendan, hydrocortisone or supplementary arginine vasopressin.

Macroscopic postmortem findings in 235 surgical intensive care patients with sepsis.

BACKGROUND: Although detailed analyses of the postmortem findings of various critically ill patient groups have been published, no such study has been performed in patients with sepsis. In this retrospective cohort study, we reviewed macroscopic postmortem examinations of surgical intensive care unit (ICU) patients who died from sepsis or septic shock. METHODS: Between 1997 and 2006, the ICU database and autopsy register were reviewed for patients who were admitted to the ICU because of sepsis/septic shock, or who developed sepsis/septic shock at a later stage during their ICU stay and subsequently died from of sepsis/septic shock. Clinical data and postmortem findings were documented in all patients. RESULTS: Postmortem results of 235 patients (84.8%) were available for statistical analysis. The main causes of death as reported in the patient history were refractory multiple organ dysfunction syndrome (51.5%) and uncontrollable cardiovascular failure (35.3%). Pathologies were detected in the lungs (89.8%), kidneys/urinary tract (60%), gastrointestinal tract (54%), cardiovascular system (53.6%), liver (47.7%), spleen (33.2%), central nervous system (18.7%), and pancreas (8.5%). In 180 patients (76.6%), the autopsy revealed a continuous septic focus. The most common continuous foci were pneumonia (41.3%), tracheobronchitis (28.9%), peritonitis (23.4%), uterine/ovarial necrosis (9.8% of female patients), intraabdominal abscesses (9.1%), and pyelonephritis (6%). A continuous septic focus was observed in 63 of the 71 patients (88.7%) who were admitted to the ICU because of sepsis/septic shock and treated for longer than 7 days. CONCLUSIONS: Relevant postmortem findings explaining death in surgical ICU patients who died because of sepsis/septic shock were a continuous septic focus in approximately 80% and cardiac pathologies in 50%. The most frequently affected organs were the lungs, abdomen, and urogenital tract. More diagnostic, therapeutic and scientific efforts should be launched to identify and control the infectious focus in patients with sepsis and septic shock.

Arterial blood pressure during early sepsis and outcome.

OBJECTIVE: To evaluate the association between arterial blood pressure (ABP) during the first 24 h and mortality in sepsis. DESIGN: Retrospective cohort study. SETTING: Multidisciplinary intensive care unit (ICU). PATIENTS AND PARTICIPANTS: A total of 274 septic patients. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Hemodynamic, and laboratory parameters were extracted from a PDMS database. The hourly time integral of ABP drops below clinically relevant systolic arterial pressure (SAP), mean arterial pressure (MAP), and mean perfusion pressure (MPP = MAP - central venous pressure) levels was calculated for the first 24 h after ICU admission and compared with 28-day-mortality. Binary and linear regression models (adjusted for SAPS II as a measure of disease severity), and a receiver operating characteristic (ROC) analysis were applied. The areas under the ROC curve were largest for the hourly time integrals of ABP drops below MAP 60 mmHg (0.779 vs. 0.764 for ABP drops below MAP 55 mmHg; P < or = 0.01) and MPP 45 mmHg. No association between the hourly time integrals of ABP drops below certain SAP levels and mortality was detected. One or more episodes of MAP < 60 mmHg increased the risk of death by 2.96 (CI 95%, 1.06-10.36, P = 0.04). The area under the ROC curve to predict the need for renal replacement therapy was highest for the hourly time integral of ABP drops below MAP 75 mmHg. CONCLUSIONS: A MAP level > or = 60 mmHg may be as safe as higher MAP levels during the first 24 h of ICU therapy in septic patients. A higher MAP may be required to maintain kidney function.

The vasopressin and copeptin response to infection, severe sepsis, and septic shock.

OBJECTIVE: To compare the course of arginine vasopressin (AVP) and copeptin plasma concentrations between patients with infection, severe sepsis, and septic shock. DESIGN: Prospective, closed-cohort study. SETTING: Twelve-bed general and surgical intensive care unit and 33-bed internal medicine ward in a university hospital. PATIENTS: Ten patients with infection, 22 with severe sepsis, and 28 with septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Hemodynamic, laboratory and clinical data were recorded daily during the first 7 days after intensive care unit or hospital admission. Parallel thereto, blood was withdrawn to determine plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations. Standard tests, a mixed effects model, and a linear regression analysis were used for statistical analysis. The AVP response was different between the three study groups (p < 0.001) but did not change over time (p = 0.12). Although patients with severe sepsis and septic shock had higher AVP levels than did patients with infection (both p < 0.001), no difference in AVP concentrations was seen between severe sepsis and septic shock patients (p = 0.98). No difference in AVP was observed between survivors and nonsurvivors at day 28 (p = 0.87). In patients with severe sepsis, serum osmolarity (p < 0.001), arterial pH (p = 0.001), lactate (p < 0.001), and Pao2 (p = 0.04) were associated with the course of AVP plasma levels, whereas it was serum osmolarity alone in patients with septic shock (p = 0.03). Plasma AVP concentrations correlated with copeptin (r = .614, p < 0.001), but this correlation was influenced by continuous veno-venous hemofiltration (p = 0.002). CONCLUSIONS: Severe sepsis induced a stronger AVP response than infection without systemic inflammation. However, the lack of a difference in AVP plasma concentrations between patients with and without shock indicates that the AVP system does not function normally in severe sepsis. Our data support the hypothesis that impaired AVP response is at least partially responsible for the failure to restore vascular tone in septic shock.

Postoperative vasopressin and copeptin levels in noncardiac surgery patients: a prospective controlled trial.

Further information on the endogenous arginine vasopressin (AVP) response in patients with postoperative systemic inflammatory response syndrome (SIRS) and vasodilatory shock would provide more insight into the pathophysiology of SIRS-associated cardiovascular failure and help indicate AVP therapy. Patients after uncomplicated abdominal surgery without SIRS (n = 10), critically ill patients after noncardiac surgery with SIRS (n = 9), and patients with SIRS plus vasodilatory shock (n = 22) were included in this prospective trial. Plasma AVP (radioimmunoassay) and copeptin (immunoluminometric assay) concentrations together with clinical parameters were documented daily during the first 7 days postoperative. The AVP response significantly differed between the three groups. Patients without SIRS had lower AVP concentrations than SIRS patients with (P = 0.001) or without shock (P = 0.003). Patients with SIRS and shock had higher AVP levels than patients with SIRS alone (P < 0.001). Arginine vasopressin decreased over time (P = 0.007) in all groups. At day 28, nonsurvivors had higher AVP levels than did survivors (P < 0.001). In SIRS patients without shock, serum osmolarity was indirectly associated with AVP levels, whereas mean arterial blood pressure and serum osmolarity were associated with AVP in SIRS patients with shock. Arginine vasopressin and copeptin correlated significantly with each other (P < 0.001; r = 0.76). In patients without hemofiltration, copeptin levels predicted 28-day mortality with high sensitivity and specificity. The postoperative AVP response in noncardiac surgery patients seems well maintained. The possibility that AVP plays a contributory role in the failure to restore vascular tone in patients with vasodilatory shock cannot be excluded but seems less important than in septic or postcardiotomy shock.

Differences in critical care practice between an industrialized and a developing country.

BACKGROUND: Few data are available on intensive care unit (ICU) patient populations and critical care medicine practices in developing countries. METHODS: This prospective study evaluated differences in patient characteristics, ICU practice, and outcome between the ICUs of a Mongolian 400-bed tertiary university hospital (MonICU) and an Austrian 429-bed secondary hospital (AutICU). Demographics, chronic health status, clinical parameters, disease and therapeutic severity scores, and outcome were documented for all patients admitted to the two ICUs during a period of four and a half months. Standard tests and multiple regression analysis were used for statistical analysis. RESULTS: A total of 203 critically ill patients were admitted to MonICU and 257 to AutICU. MonICU patients had fewer chronic diseases than AutICU patients (0.9 +/- 0.8 vs. 2.7 +/- 1.5, P < 0.001) but more frequently suffered from tuberculosis (2.5% vs. 0%, P = 0.01) and more frequently had never been medically examined before ICU admission (10.8% vs. 0%, P < 0.001). Admission diagnoses differed both in type and relative proportions in the two ICUs (P < 0.001). Admission of MonICU patients was more frequently unplanned (69% vs. 50.2%, P < 0.001), and although disease was more severe in these patients they received fewer therapeutic interventions than the AutICU patients. Overall mortality was higher in the MonICU patients (19.7 vs. 6.2%, P < 0.001). CONCLUSIONS: Patient characteristics and ICU practices varied significantly between the two ICUs. Mortality was substantially greater at MonICU, particularly among patients suffering from multiple-organ dysfunction. Strategies to improve the care of critically ill patients at MonICU should address both system- and staff-related problems, improve acceptance of the ICU service among physicians of other disciplines and upgrade the training of ICU staff.

Report from Mongolia -- How much do we know about the incidence of rare cases in less developed countries: a case series.

INTRODUCTION: Case reports are important instruments to describe rare disease conditions and give a rough estimation of their global incidence. Even though collected in international databases, most case reports are published by clinicians from industrialized nations and little is known about the incidence of rare cases in less developed countries, which are home to 75% of the world's population. CASE PRESENTATION: We present seven patients who suffered from diseases which are either considered to be rare or have not yet been described before according to international databases, but occurred during a 5-month period in one intensive care unit of a less developed country. During the observation period, patients with a spontaneous infratentorial subdural hematoma (Asian, female, 41 years), general exanthema and acute renal failure after diesel ingestion (Asian, male, 30 years), transient cortical blindness complicating hepatic encephalopathy (Asian, female, 49 years), Fournier gangrene complicating acute necrotizing pancreatitis (Asian, male, 37 years), acute renal failure due to acetic acid intoxication (Asian, male, 42 years), haemolytic uremic syndrome following septic abortion (Asian, female, 45 years), and a metal needle as an unusual cause of chest pain (Asian, male, 41 years) were treated. According to the current literature, all seven disease conditions are considered either rare or have so far not yet been reported. CONCLUSION: The global incidence of rare cases may be underestimated by contemporary international databases. Diseases which are currently considered to be rare in industrialized nations may occur at a higher frequency in less developed countries. Reasons may not only be a geographically different burden of certain diseases, limited diagnostic and therapeutic facilities, but also a relevant publication bias.

Combined milrinone and enteral metoprolol therapy in patients with septic myocardial depression.

INTRODUCTION: The multifactorial etiology of septic cardiomyopathy is not fully elucidated. Recently, high catecholamine levels have been suggested to contribute to impaired myocardial function. METHODS: This retrospective analysis summarizes our preliminary clinical experience with the combined use of milrinone and enteral metoprolol therapy in 40 patients with septic shock and cardiac depression. Patients with other causes of shock or cardiac failure, patients with beta-blocker therapy initiated more than 48 hours after shock onset, and patients with pre-existent decompensated congestive heart failure were excluded. In all study patients, beta blockers were initiated only after stabilization of cardiovascular function (17.7 +/- 15.5 hours after shock onset or intensive care unit admission) in order to decrease the heart rate to less than 95 beats per minute (bpm). Hemodynamic data and laboratory parameters were extracted from medical charts and documented before and 6, 12, 24, 48, 72, and 96 hours after the first metoprolol dosage. Adverse cardiovascular events were documented. Descriptive statistical methods and a linear mixed-effects model were used for statistical analysis. RESULTS: Heart rate control (65 to 95 bpm) was achieved in 97.5% of patients (n = 39) within 12.2 +/- 12.4 hours. Heart rate, central venous pressure, and norepinephrine, arginine vasopressin, and milrinone dosages decreased (all P < 0.001). Cardiac index and cardiac power index remained unchanged whereas stroke volume index increased (P = 0.002). In two patients (5%), metoprolol was discontinued because of asymptomatic bradycardia. Norepinephrine and milrinone dosages were increased in nine (22.5%) and six (15%) patients, respectively. pH increased (P < 0.001) whereas arterial lactate (P < 0.001), serum C-reactive protein (P = 0.001), and creatinine (P = 0.02) levels decreased during the observation period. Twenty-eight-day mortality was 33%. CONCLUSION: Low doses of enteral metoprolol in combination with phosphodiesterase inhibitors are feasible in patients with septic shock and cardiac depression but no overt heart failure. Future prospective controlled trials on the use of beta blockers for septic cardiomyopathy and their influence on proinflammatory cytokines are warranted.