Correction to: A decade of progress in critical care echocardiography: a narrative review.

The original version of this article unfortunately contained a mistake.

A decade of progress in critical care echocardiography: a narrative review.

INTRODUCTION: This narrative review focusing on critical care echocardiography (CCE) has been written by a group of experts in the field, with the aim of outlining the state of the art in CCE in the 10 years after its official recognition and definition. RESULTS: In the last 10 years, CCE has become an essential branch of critical care ultrasonography and has gained general acceptance. Its use, both as a diagnostic tool and for hemodynamic monitoring, has increased markedly, influencing contemporary cardiorespiratory management. Recent studies suggest that the use of CCE may have a positive impact on outcomes. CCE may be used in critically ill patients in many different clinical situations, both in their early evaluation of in the emergency department and during intensive care unit (ICU) admission and stay. CCE has also proven its utility in perioperative settings, as well as in the management of mechanical circulatory support. CCE may be performed with very simple diagnostic objectives. This application, referred to as basic CCE, does not require a high level of training. Advanced CCE, on the other hand, uses ultrasonography for full evaluation of cardiac function and hemodynamics, and requires extensive training, with formal certification now available. Indeed, recent years have seen the creation of worldwide certification in advanced CCE. While transthoracic CCE remains the most commonly used method, the transesophageal route has gained importance, particularly for intubated and ventilated patients. CONCLUSION: CCE is now widely accepted by the critical care community as a valuable tool in the ICU and emergency department, and in perioperative settings.

Diagnostic workup, etiologies and management of acute right ventricle failure : A state-of-the-art paper.

INTRODUCTION: This is a state-of-the-art article of the diagnostic process, etiologies and management of acute right ventricular (RV) failure in critically ill patients. It is based on a large review of previously published articles in the field, as well as the expertise of the authors. RESULTS: The authors propose the ten key points and directions for future research in the field. RV failure (RVF) is frequent in the ICU, magnified by the frequent need for positive pressure ventilation. While no universal definition of RVF is accepted, we propose that RVF may be defined as a state in which the right ventricle is unable to meet the demands for blood flow without excessive use of the Frank-Starling mechanism (i.e. increase in stroke volume associated with increased preload). Both echocardiography and hemodynamic monitoring play a central role in the evaluation of RVF in the ICU. Management of RVF includes treatment of the causes, respiratory optimization and hemodynamic support. The administration of fluids is potentially deleterious and unlikely to lead to improvement in cardiac output in the majority of cases. Vasopressors are needed in the setting of shock to restore the systemic pressure and avoid RV ischemia; inotropic drug or inodilator therapies may also be needed. In the most severe cases, recent mechanical circulatory support devices are proposed to unload the RV and improve organ perfusion CONCLUSION: RV function evaluation is key in the critically-ill patients for hemodynamic management, as fluid optimization, vasopressor strategy and respiratory support. RV failure may be diagnosed by the association of different devices and parameters, while echocardiography is crucial.

Therapeutic advances in the treatment of Peyronie's disease.

Peyronie's disease (PD) is an under-diagnosed condition with prevalence in the male population as high as 9%. It is a localized connective tissue disorder of the penis characterized by scarring of the tunica albuginea. Its pathophysiology, however, remains incompletely elucidated. For the management of the acute phase of PD, there are currently numerous available oral drugs, but the scientific evidence for their use is weak. In terms of intralesional injections, collagenase clostridium histolyticum is currently the only Food and Drug Administration-approved drug for the management of patients with PD and a palpable plaque with dorsal or dorsolateral curvature >30°. Other available intralesional injectable drugs include verapamil and interferon-alpha-2B, however, their use is considered off-label. Iontophoresis, shockwave therapy, and radiation therapy have also been described with unconvincing results, and as such, their use is currently not recommended. Traction therapy, as part of a multimodal approach, is an underused additional tool for the prevention of PD-associated loss of penile length, but its efficacy is dependent on patient compliance. Surgical therapy remains the gold standard for patients in the chronic phase of the disease. In patients with adequate erectile function, tunical plication and/or incision/partial excision and grafting can be offered, depending on degree of curvature and/or presence of destabilizing deformity. In patients with erectile dysfunction non-responsive to oral therapy, insertion of an inflatable penile prosthesis with or without straightening procedures should be offered.

Prognostic implications of tissue oxygen saturation in human septic shock.

PURPOSE: To analyze the prognostic value of tissue oxygen saturation (StO(2)) in septic shock patients with restored mean arterial pressure (MAP). METHODS: This was a prospective observational study of patients admitted to the ICU in the early phase of septic shock, after restoration of MAP. Demographic data, severity score, hemodynamics, blood lactate, acid-base status, and StO(2) were measured at inclusion followed by a transient vascular occlusion test (VOT) to obtain the StO(2)-deoxygenation (DeOx) and StO(2)-reoxygenation (ReOx) rates. Sequential organ failure assessment (SOFA) score was measured at inclusion and after 24 h. RESULTS: Thirty-three patients were studied. StO(2) was 76 ± 10%, DeOx -12.2 ± 4.2%/min, and ReOx 3.02 ± 1.70%/s. MAP showed a significant correlation with VOT-derived slopes (r = -0.4, p = 0.04 for DeOx; and r = 0.55, p < 0.01 for ReOx). After 24 h, 17 patients (52%) had improved SOFA scores. Patients who did not improve their SOFA showed less negative DeOx values at inclusion. The association between DeOx and SOFA evolution was not affected by MAP. Both DeOx and ReOx impairment correlated with longer ICU stay (r = 0.44, p = 0.05; and r = -0.43, p = 0.05, respectively). CONCLUSIONS: In a population of septic shock patients with restored MAP, impaired DeOx was associated with no improvement in organ failures after 24 h. Decrements in DeOx and ReOx were associated with longer ICU stay. DeOx and ReOx were linked to MAP, and thus, their interpretation needs to be made relative to MAP.

Dapoxetine for premature ejaculation.

Premature ejaculation (PE) is the most common form of male sexual dysfunction, with an estimated worldwide prevalence of 20­30%.1 Although PE is not life threatening, it has significant impact on quality of life. The fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR)defines PE as "persistent or recurrent ejaculation with minimal sexual stimulation before, on, or shortly after penetration and before the person wishes it" that "causes marked distress or interpersonal difficulty" and "is not due exclusively to the direct effects of a substance."2 The International Society for Sexual Medicine, which recently modified the definition to include the threshold ejaculatory latency time, defines PEas "male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within 1 min of vaginal penetration; the inability to delay ejaculation on all or nearly all vaginal penetrations; and negative personal consequences such as distress, bother, frustration, and/or the avoidance of sexual intimacy."3 The lack of ejaculatory control is consistent among all clinical definitions of PE and is a highly sensitive predictor of the condition.

Fluid and volume monitoring.

BACKGROUND: Fluid resuscitation is not only used to prevent acute kidney injury (AKI) but fluid management is also a cornerstone of treatment for patients with established AKI and renal failure. Ultrafiltration removes volume initially from the intravascular compartment inducing a relative degree of hypovolemia. Normal reflex mechanisms attempt to sustain blood pressure constant despite marked changes in blood volume and cardiac output. Thus, compensated shock with a normal blood pressure is a major cause of AKI or exacerbations of AKI during ultrafiltration. METHODS: We undertook a systematic review of the literature using MEDLINE, Google Scholar and PubMed searches. We determined a list of key questions and convened a 2-day consensus conference to develop summary statements via a series of alternating breakout and plenary sessions. In these sessions, we identified supporting evidence and generated clinical practice recommendations and/or directions for future research. RESULTS: We defined three aspects of fluid monitoring: i) normal and pathophysiological cardiovascular mechanisms; ii) measures of volume responsiveness and impending cardiovascular collapse during volume removal, and; iii) measured indices of each using non-invasive and minimally invasive continuous and intermittent monitoring techniques. The evidence documents that AKI can occur in the setting of normotensive hypovolemia and that under-resuscitation represents a major cause of both AKI and mortality ion critically ill patients. Traditional measures of intravascular volume and ventricular filling do not predict volume responsiveness whereas dynamic functional hemodynamic markers, such as pulse pressure or stroke volume variation during positive pressure breathing or mean flow changes with passive leg raising are highly predictive of volume responsiveness. Numerous commercially-available devices exist that can acquire these signals. CONCLUSIONS: Prospective clinical trials using functional hemodynamic markers in the diagnosis and management of AKI and volume status during ultrafiltration need to be performed. More traditional measure of preload be abandoned as marked of volume responsiveness though still useful to assess overall volume status.

Targets for resuscitation from shock.

Resuscitation from circulatory and respiratory failure represent mainstays of emergency and critical care management. Importantly, no amount of resuscitative effort will be successful in promoting patient survival if the primary reason for the shock state is not identified and treated, independent of resuscitation. Having said that, aggressive resuscitation to normal functional levels of blood flow and organ perfusion pressure during the first 6 hours following the development of shock improves outcome both in patients with trauma or sepsis. However, clinical studies have demonstrated that restoration of total blood flow to supranormal levels in subjects with established shock that has been present for over 6 hours does not improve survival. Still, some defined clinical targets are essential in these patients as well to prevent further organ injury due to ischemia and its associated inflammatory response. Thus, the rapid restoration of normal hemodynamics by conventional means, including fluid resuscitation and surgical repair, results in a better log term outcome than inadequate or delayed resuscitative efforts. Clear initial targets for resuscitation are a mean arterial pressure > 60 mm Hg, and a cardiac output and O(2) transport to the body adequate enough to prevent tissue hypoperfusion. The level of cardiac output needed to achieve this goal is probably different among subjects and within subjects over time. Indirect signposts of adequate perfusion, such as venous O2 saturation, mentation, urine output and local measures of tissue blood flow are useful in monitoring this response.

Nitric oxide contamination of hospital compressed air improves gas exchange in patients with acute lung injury.

OBJECTIVE: We tested the hypothesis that NO contamination of hospital compressed air also improves PaO(2) in patients with acute lung injury (ALI) and following lung transplant (LTx). DESIGN: Prospective clinical study. SETTING: Cardiothoracic intensive care unit. PATIENTS: Subjects following cardiac surgery (CABG, n=7); with ALI (n=7), and following LTx (n=5). INTERVENTIONS: Four sequential 15-min steps at a constant FiO(2) were used: hospital compressed air-O(2) (H1), N(2)-O(2) (A1), repeat compressed air-O(2) (H2), and repeat N(2)-O(2) (A2). MEASUREMENTS AND RESULTS: NO levels were measured from the endotracheal tube. Cardiorespiratory values included PaO(2) were measured at the end of each step. FiO(2) was 0.46+/-0.05, 0.53+/-0.15, and 0.47+/-0.06 (mean+/-SD) for three groups, respectively. Inhaled NO levels during H1 varied among subjects (30-550 ppb, 27-300 ppb, and 5-220 ppb, respectively). Exhaled NO levels were not detected in 4/7 of CABG (0-300 ppb), 3/6 of ALI (0-140 ppb), and 3/5 of LTx (0-59 ppb) patients during H1, whereas during A1 all but one patient in ALI and three CABG patients had measurable exhaled NO levels (P<0.05). Small but significant decreases in PaO(2) occurred for all groups from H1 to A1 and H2 to A2 (132-99 Torr and 128-120 Torr, P <0.01, respectively). There was no correlation between inhaled NO during H1 and exhaled NO during A1 or the change in PaO(2) from H1 to A1. CONCLUSIONS: Low-level NO contamination improves PaO(2) in patients with ALI and following LTx.

Mitochondrial membrane potential and apoptosis peripheral blood monocytes in severe human sepsis.

UNLABELLED: Reduced mitochondrial membrane potential (Delta(Psi)m), which is considered as an initial and irreversible step towards apoptosis, as well as cell death regulating proteins, such as Fas, Hsp70, or Bcl-2, may play an important role in sepsis. We studied the relationship between sepsis severity and peripheral blood monocyte Delta(Psi)m, cell death (necrosis and apoptosis), soluble Fas ligand, Hsp70, and Bcl-2 expression over time in 18 patients with sepsis, and compared these data with those of a group of 17 healthy control subjects. All measurements were performed within 3 d of the onset of severe sepsis (T1), then 7 to 10 d later (T2), and finally at hospital discharge (T3). Delta(Psi)m was expressed as the percent monocytes with altered Delta(Psi)m (%Delta(Psi)m). Patients with sepsis had greater %Delta(Psi)m at T1 and T2 but not at T3 (14.6 +/- 2.6% and 15.9 +/- 2%, respectively, versus control 6.6 +/- 0.2%, p < 0.01). Septic patients exhibited greater cell death in their monocytes and had greater Hsp70 expression only at T1. Bcl-2 levels were similar in septic and control subjects. Comparing survivors with non-survivors of sepsis, nonsurvivors had a greater %Delta(Psi)m at T1 (26.4 +/- 5.3% versus 10.1 +/- 2.7%, p < 0.01) and a significant decrease in Bcl-2 expression, whereas no difference was found in Hsp70 levels. These results indicate that mitochondrial dysfunction and subsequent cell death occur in severe sepsis and suggest that %Delta(Psi)m is a marker of severity in human sepsis. KEYWORDS: mitochondria; apoptosis; sepsis; heat-shock protein 70; proto-oncogene protein c-Bcl-2

Implications of arterial pressure variation in patients in the intensive care unit.

Positive-pressure ventilation alters stroke volume by transiently increasing intrathoracic pressure and thereby decreasing preload. This phasic variation in stroke volume results in a cyclic fluctuation in arterial pressure with a phase length equal to the respiratory rate. Measuring ventilation-induced arterial pressure variation allows the clinician to predict the cardiovascular response to changes in intravascular volume status. Thus, one may predict preload responsiveness because the greater the amount of ventilation-associated arterial pressure variation, the greater the patient's preload responsiveness. This variation in arterial pressure can been defined as a variation in either systolic pressure or pulse pressure. Although pulse pressure gives a clearer signal, systolic pressure variation may be easier to measure bedside without invasive hemodynamic monitoring. Newer methods of quantifying this arterial pressure variation include the respiratory systolic variation test, which can performed without an apneic baseline, and the pulse pressure variation, a potentially more accurate measure of preload responsiveness.

Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care.

OBJECTIVE: To determine the incidence, cost, and outcome of severe sepsis in the United States. DESIGN: Observational cohort study. SETTING: All nonfederal hospitals (n = 847) in seven U.S. states. PATIENTS: All patients (n = 192,980) meeting criteria for severe sepsis based on the International Classification of Diseases, Ninth Revision, Clinical Modification. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We linked all 1995 state hospital discharge records (n = 6,621,559) from seven large states with population and hospital data from the U.S. Census, the Centers for Disease Control, the Health Care Financing Administration, and the American Hospital Association. We defined severe sepsis as documented infection and acute organ dysfunction using criteria based on the International Classification of Diseases, Ninth Revision, Clinical Modification. We validated these criteria against prospective clinical and physiologic criteria in a subset of five hospitals. We generated national age- and gender-adjusted estimates of incidence, cost, and outcome. We identified 192,980 cases, yielding national estimates of 751,000 cases (3.0 cases per 1,000 population and 2.26 cases per 100 hospital discharges), of whom 383,000 (51.1%) received intensive care and an additional 130,000 (17.3%) were ventilated in an intermediate care unit or cared for in a coronary care unit. Incidence increased >100-fold with age (0.2/1,000 in children to 26.2/1,000 in those >85 yrs old). Mortality was 28.6%, or 215,000 deaths nationally, and also increased with age, from 10% in children to 38.4% in those >85 yrs old. Women had lower age-specific incidence and mortality, but the difference in mortality was explained by differences in underlying disease and the site of infection. The average costs per case were $22,100, with annual total costs of $16.7 billion nationally. Costs were higher in infants, nonsurvivors, intensive care unit patients, surgical patients, and patients with more organ failure. The incidence was projected to increase by 1.5% per annum. CONCLUSIONS: Severe sepsis is a common, expensive, and frequently fatal condition, with as many deaths annually as those from acute myocardial infarction. It is especially common in the elderly and is likely to increase substantially as the U.S. population ages.

Quantifying learning in medical students during a critical care medicine elective: a comparison of three evaluation instruments.

OBJECTIVE: To compare three different evaluative instruments and determine which is able to measure different aspects of medical student learning. DESIGN: Student learning was evaluated by using written examinations, objective structured clinical examination, and patient simulator that used two clinical scenarios before and after a structured critical care elective, by using a crossover design. PARTICIPATION: Twenty-four 4th-yr students enrolled in the critical care medicine elective. INTERVENTIONS: All students took a multiple-choice written examination; evaluated a live simulated critically ill patient, requested data from a nurse, and intervened as appropriate at different stations (objective structured clinical examination); and evaluated the computer-controlled patient simulator and intervened as appropriate. MEASUREMENTS AND MAIN RESULTS: Students' knowledge was assessed by using a multiple-choice examination containing the same data incorporated into the other examinations. Student performance on the objective structured clinical examination was evaluated at five stations. Both objective structured clinical examination and simulator tests were videotaped for subsequent scores of responses, quality of responses, and response time. The videotapes were reviewed for specific behaviors by faculty masked to time of examination. Students were expected to perform the following: a) assess airway, breathing, and circulation; b) prepare a mannequin for intubation; c) provide appropriate ventilator settings; d) manage hypotension; and e) request, interpret, and provide appropriate intervention for pulmonary artery catheter data. Students were expected to perform identical behaviors during the simulator examination; however, the entire examination was performed on the whole-body computer-controlled mannequin. The primary outcome measure was the difference in examination scores before and after the rotation. The mean preelective scores were 77 +/- 16%, 47 +/- 15%, and 41 +/- 14% for the written examination, objective structured clinical examination, and simulator, respectively, compared with 89 +/- 11%, 76 +/- 12%, and 62 +/- 15% after the elective (p <.0001). Prerotation scores for the written examination were significantly higher than the objective structured clinical examination or the simulator; postrotation scores were highest for the written examination and lowest for the simulator. CONCLUSION: Written examinations measure acquisition of knowledge but fail to predict if students can apply knowledge to problem solving, whereas both the objective structured clinical examination and the computer-controlled patient simulator can be used as effective performance evaluation tools.

Sepsis: a pro- and anti-inflammatory disequilibrium syndrome.

Severe sepsis and probably most prolonged critical illnesses reflect a paradox of combined increased activation and depression of the immune apparatus. The increased activation of the inflammatory response is evidenced from the increased levels of circulating proinflammatory cytokines in the blood, increased endothelial activation with increased expression of inducible nitric oxide synthase, and increased de novo CD11b expression on circulating immune effector cells, such as PMNs, monocytes and lymphocytes. However, coexisting with this proinflammatory process is a profound anti-inflammatory state characterized by increased circulating levels of anti-inflammatory species that both directly block the binding of proinflammatory stimuli to their cell surface receptors (IL-1ra, soluble TNF receptors) and also induce an anti-inflammatory state on their own (IL-10, TFG-beta). This humoral anti-inflammatory state is mirrored at the cellular levels by decreased monocyte ability to process antigen, characterized by a reduced HLA-DR expression and impaired PMN upregulation in response to clearly proinflammatory stimuli. Accordingly, severe sepsis reflects a combined pro- and anti-inflammatory state. Both the pro- and anti-inflammatory arms have protective and destructive aspects, making their modulation by treatment less predictable than if their actions were purely beneficial or detrimental.