Heart rate reduction with esmolol is associated with improved arterial elastance in patients with septic shock: a prospective observational study.

PURPOSE: Ventricular-arterial (V-A) decoupling decreases myocardial efficiency and is exacerbated by tachycardia that increases static arterial elastance (Ea). We thus investigated the effects of heart rate (HR) reduction on Ea in septic shock patients using the beta-blocker esmolol. We hypothesized that esmolol improves Ea by positively affecting the tone of arterial vessels and their responsiveness to HR-related changes in stroke volume (SV). METHODS: After at least 24 h of hemodynamic optimization, 45 septic shock patients, with an HR ≥95 bpm and requiring norepinephrine to maintain mean arterial pressure (MAP) ≥65 mmHg, received a titrated esmolol infusion to maintain HR between 80 and 94 bpm. Ea was calculated as MAP/SV. All measurements, including data from right heart catheterization, echocardiography, arterial waveform analysis, and norepinephrine requirements, were obtained at baseline and at 4 h after commencing esmolol. RESULTS: Esmolol reduced HR in all patients and this was associated with a decrease in Ea (2.19 ± 0.77 vs. 1.72 ± 0.52 mmHg l(-1)), arterial dP/dt max (1.08 ± 0.32 vs. 0.89 ± 0.29 mmHg ms(-1)), and a parallel increase in SV (48 ± 14 vs. 59 ± 18 ml), all p < 0.05. Cardiac output and ejection fraction remained unchanged, whereas norepinephrine requirements were reduced (0.7 ± 0.7 to 0.58 ± 0.5 µg kg(-1) min(-1), p < 0.05). CONCLUSIONS: HR reduction with esmolol effectively improved Ea while allowing adequate systemic perfusion in patients with severe septic shock who remained tachycardic despite standard volume resuscitation. As Ea is a major determinant of V-A coupling, its reduction may contribute to improving cardiovascular efficiency in septic shock.

A cross-sectional nationwide survey on esophageal atresia and tracheoesophageal fistula.

BACKGROUND: Our study aims at disclosing epidemiology and most relevant clinical features of esophageal atresia (EA) pointing to a model of multicentre collaboration. METHODS: A detailed questionnaire was sent to all Italian Units of pediatric surgery in order to collect data of patients born with EA between January and December 2012. The results were crosschecked by matching date and place of birth of the patients with those of diagnosis-related group provided by the Italian Ministry of Health (MOH). RESULTS: A total of 146 questionnaires were returned plus a further 32 patients reported in the MOH database. Basing on a total of 178 patients with EA born in Italy in 2012, the incidence of EA was calculated in 3.33 per 10,000 live births. Antenatal diagnosis was suspected in 29.5% patients. 55.5% showed associated anomalies. The most common type of EA was Gross type C (89%). Postoperative complications occurred in 37% of type C EA and 100% of type A EA. A 9.5% mortality rate was reported. CONCLUSIONS: This is the first Italian cross-sectional nationwide survey on EA. We can now develop shared guidelines and provide more reliable prognostic expectations for our patients.

Brain-heart crosstalk: the many faces of stress-related cardiomyopathy syndromes in anaesthesia and intensive care.

Neurogenic stress cardiomyopathy (NSC) is a well-known syndrome complicating the early phase after an acute brain injury, potentially affecting outcomes. This article is a review of recent data on the putative role of localization and lateralization of brain lesions in NSC, cardiac innervation abnormalities, and new polymorphisms and other genetic causes of the sympathetic nervous system over-activity. Concerns regarding the management of stress-related cardiomyopathy syndromes during the perioperative period are also discussed. Future clinical research should explore whether specific factors explain different patient susceptibilities to the disease and should be directed towards early identification and stratification of patients at risk, so that such patients can be more carefully monitored and appropriately managed in critical care and during the perioperative period.

Epidemiology and outcome of sepsis syndromes in Italian ICUs: a muticentre, observational cohort study in the region of Piedmont.

BACKGROUND: Sepsis is an important cause of mortality and morbidity in the intensive care unit (ICU). We performed a study to describe the epidemiology of sepsis syndromes in patients admitted to ICUs of the Piedmont region. METHODS: In this prospective, multicentre, observational study, all 3902 patients admitted to a network of 24 ICUs from 17 hospitals during a 180 day period (April 3-September 29, 2006) were included. Patients were followed from the first day of admission until death or ICU discharge. RESULTS: The incidence of sepsis during the ICU stay was 11.4% (N.=446), corresponding to an incidence of 25 cases/100,000 inhabitants/year; 141 (31.6%) patients had only sepsis, 160 patients had severe sepsis (35.9%) and 145 patients (32.5%) had septic shock In 227 patients (50.9%), sepsis was observed within 48 hours after admission to the ICU, and 219 patients (49.1%) developed ICU-acquired sepsis. The main sources of infection were the lungs, abdomen, and urinary tract. ICU mortality was higher (41.3 vs. 17.3%, P<0.0001) and the median ICU length of stay longer (15 vs. 2 days, P<0.0001) in patients with sepsis than in those without sepsis. The mortality rate increased with the severity of sepsis. ICU-acquired sepsis was associated with higher ICU mortality rates than sepsis occurring within 48 hours of ICU admission (49.8 vs. 33.0%, P<0.0001). CONCLUSION: Sepsis is a common occurrence in critically ill patients. Our data underscore the regional variability in the epidemiology and outcome of sepsis syndromes and may be useful to guide appropriate resource allocation.

Donation after cardiac death: is a "paradigm shift" feasible in Italy?

Donation after cardiac death (DCD) is one of the growing strategies to overcome the problem of organ shortage. Cardiac death is defined as "irreversible cessation of circulatory and respiratory function"; the time interval to define irreversibility of cardiac death, the peculiarity of consent, and the framework of end-of-life decision making are the most compelling ethical issues which have been raised with DCD. National protocols that balance medical, ethical, and social issues are mandatory to guide transplant care professionals. In Italy, the 20 min cardiac arrest demonstrated by continuous electrocardiography recording is the time interval necessary for death diagnosis based on cardiopulmonary criteria. This time negatively affects donation after cardiac death because warm ischemic time (WIT) - the most important predictor of grafts' poor outcome - is prolonged. However, this time seems to be prudential to define the irreversibility of death and to respect the "dead donor rule", as established by the National Committee of Bioethics. National reference protocols regulating DCD practice are therefore a compelling issue.

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Sleep disturbances in the critically ill patients: role of delirium and sedative agents.

BACKGROUND: Impairment of sleep quality and quantity has been described in critically ill patients. Delirium, an organ dysfunction that affects outcome of the critically ill patients, is characterized by an acute onset of impaired cognitive function, visual hallucinations, delusions, and illusions. These symptoms resemble the hypnagogic hallucinations and wakeful dreams seen in patients with neurological degenerative disorders and suffering of disorders of rapid eye movement (REM) sleep. We assessed the characteristics of sleep disruption in a cohort of surgical critically ill patients examining the hypothesis that severe impairments of rapid eyes movement (REM) sleep are associated to delirium. METHODS: Surgical patients admitted to the intensive care units of the San G. Battista Hospital (University of Turin) were enrolled. Once weaning was initiated, sleep was recorded for one night utilizing standard polysomnography. Clinical status, laboratory data on admission, co-morbidities and duration of mechanical ventilation were recorded. Patients were a priori classified as having a "severe REM reduction" or "REM reduction" if REM was higher or lower than 6% of the total sleep time (TST), respectively. Occurrence of delirium during intensive care unit (ICU) stay was identified by CAM-ICU twice a day. Multivariate forward stepwise logistic regression analysis was performed with sleep ("severe REM reduction" vs. "REM reduction") as the a priori dependent factor. RESULTS: REM sleep amounted to 44 (16-72) minutes [11 (8-55) % of the TST] in 14 patients ("REM reduction") and to 2.5 (0-36) minutes [1 (0-6) % of the TST] in the remaining 15 patients ("severe REM reduction") (P = 0.0004). SAPS II on admission was higher in " severely REM deprived" then in "REM deprived" patients. Delirium was present in 11 patients (73.3%) of the patients with "severe REM reduction" and lasted for a median of 3 (0-11) days before sleep assessment, while only one patient having "REM reduction" developed delirium that lasted for 1 day. The factors independently associated with a higher risk of developing "severe REM reduction" were delirium and daily dosage of lorazepam. CONCLUSION: The present study shows that while all critically ill patients present a profound fragmentation of sleep with a high frequency of arousals and awakenings and a reduction of REM sleep, a percentage of patients present an extremely severe reduction of REM sleep. Delirium and daily dosage of lorazepam are the factors independently associated to extremely severe REM sleep reduction.

The effects of inhaled nitric oxide after lung transplantation.

Primary graft failure (PGF) is one of the major complications that occurs immediately following lung transplantation and greatly contributes to increased morbidity and mortality. The incidence of PGF is correlated with a marked decline in endogenous nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) levels. Therefore, the administration of NO during lung transplantation has been proposed as a possible therapeutic treatment to prevent or attenuate PGF pathogenesis. Despite the initial positive results of experimental and uncontrolled clinical trials, recent randomized clinical trials do not support the prophylactic administration of inhaled nitric oxide (iNO) for the prevention of PGF following lung transplantation under the conditions tested. Nonetheless, there is evidence that iNO administration during PGF can improve oxygenation and reduce pulmonary hypertension without altering systemic vascular resistance. This suggests that iNO may prevent the need for extracorporeal membrane oxygenation (ECMO) during the hypoxic phase of PGF. During the intraoperative phase of transplantation, one-lung ventilation (OLV) and pulmonary artery clamping usually increase PVR, causing decreased right ventricular function and hemodynamic instability. The administration of iNO during these lung transplant procedures could decrease right ventricular dysfunction by reducing PVR and help to avoid the use of cardiopulmonary bypass.

Management to optimize organ procurement in brain dead donors.

The demand for donor organs continues to exceed the number of organs available for transplantation. Many reasons may account for this discrepancy, such as the lack of consent, the absence of an experienced coordinator team able to solve logistical problems, the use of strict donor criteria, and suboptimal, unstandardized critical care management of potential organ donors. This has resulted in efforts to improve the medical care delivered to potential organ donors, so as to reduce organ shortages, improve organ procurement, and promote graft survival. The physiological changes that follow brain death entail a high incidence of complications jeopardizing potentially transplantable organs. Adverse events include cardiovascular changes, endocrine and metabolic disturbances, and disruption of internal homeostasis. Brain death also upregulates the release of pro-inflammatory molecules. Recent findings support the hypothesis that a preclinical lung injury characterized by an enhanced inflammatory response is present in potential donors and may predispose recipients to an adverse clinical prognosis following lung transplantation. In clinical practice, hypotension, diabetes insipidus, relative hypothermia, and natremia are more common than disseminated intravascular coagulation, cardiac arrhythmias, pulmonary oedema, acute lung injury, and metabolic acidosis. Strategies for the management of organ donors exist and consist of the normalization of donor physiology. Management has been complicated by the recent use of ''marginal'' donors and donors of advanced age or with ''extended'' criteria. Current guidelines suggest that the priority of critical care management for potential organ donors should be shifted from a ''cerebral protective'' strategy to a multimodal strategy aimed to preserve peripheral organ function.

[Validity of urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) as biomarker of exposure to very low concentrations of carbon disulphide: preliminary results]. / Validiti dell'acido 2-tiotiazolidin-4-carbossilico (TTCA) urinario quale indicatore biologico dell'esposizione a concentrazioni molto basse di solfuro di carbonio: risultati preliminori.

The possibility to use urinary 2-thiothiazolidine-4-carboxylic acid (TTCA) as biomarker of occupational exposure to very low doses of carbon disulphide (CS2) was evaluated preliminarily in 10 workers employed in a chemical plant where rubber vulcanization accelerators are produced, and in 10 workers, residents in the same geographical area and not occupationally exposed to CS2 and dithiocarbamates (DTC). Exposure to airborne CS2 was assessed, only for exposed workers, by both personal and area samplers. For the determination of TTCA, a spot urine sample was collected for each worker, exposed and non exposed, at the end of work-shift. A questionnaire probing lifestyle and dietary habits and non occupational exposure to CS2 and DTC was administered to all workers involved in the study. Environmental exposure to CS2 in 2007 ranged between 0.21 mg/m3 and 0.73 mg/m3 for personal sampling, and between 0.23 mg/m3 and 0.41 mg/m3 for area sampling. Urinary TTCA levels resulted very low and did not show any significant difference between exposed (Median: 10.8 microg/g creat; Range: 6.1-26.4 microg/g creat) and non exposed workers (Median: 9.3 microg/g creat; Range: 3.0-33.0 microg/g creat), while higher, but not significant concentrations of TTCA were observed in smokers than in non smokers (p = 0.09). No correlation was found between urinary TTCA levels and environmental exposure to CS2, age, body mass index, smoking and dietary habits. In conclusion, the low sensibility and specificity in the assessment of occupational exposure to low doses of CS2 in workers compared to general population subjects, makes urinary TTCA a biomarker with a low usefulness in biological monitoring. ACGIH, besides, should also introduce "B" (background) notation, at present not considered for the BEI indicated for urinary TTCA.