Pulse pressure variation as a predictor of fluid responsiveness in mechanically ventilated patients with spontaneous breathing activity: a pragmatic observational study.

INTRODUCTION: Pulse pressure variation predicts fluid responsiveness in mechanically ventilated patients passively adapted to the ventilator. Its usefulness in actively breathing ventilated patients was examined only by few studies with potential methodological shortcomings. This study sought to describe the performance of pulse pressure variation as a predictor of fluid responsiveness in hypotensive critically ill patients who trigger the ventilator. METHODS: We studied forty two hypotensive, mechanically ventilated patients with documented spontaneous breathing activity in whom a fluid challenge was deemed necessary by the attending physician. All patients were ventilated with a Maquet Servo-i Ventilator in different ventilatory modes with a flow-regulated inspiratory trigger set on position 4. Pulse pressure variation, mean and systolic arterial pressure were observed before and after the fluid challenge, which consisted in the intravenous administration of a 250 ml bolus of 6% hetastarch. Fluid responsiveness was defined as a more than 15% increase in arterial pressure after volume expansion. RESULTS: The area under the receiver operator characteristic curve for pulse pressure variation was 0.87 (95% CI 0.74 -0.99; p<0.0001) and the grey zone limits were 10% and 15%. Pulse pressure variation was correlated with increase in systolic arterial pressure (r2=0.32; p<0.001) and mean arterial pressure (r2=0.10; p=0.037). CONCLUSIONS: Pulse pressure variation predicts fluid responsiveness in patients who actively interact with a Servo-i ventilator with a flow-regulated inspiratory trigger set on position 4.

Early predictive factors on mortality in head injured patients: a retrospective analysis of 112 traumatic brain injured patients.

AIM: Early hyperglycemia is a feature of traumatic brain injured (TBI) patients. The aim of our study was to analyze the impact of early hyperglycemia on in-ICU mortality in isolated TBI and its correlations with other factors responsible for secondary injury. METHODS: We studied admission values (AV) and worse values in the first 48 hours (WV 48 h) of 112 ICU TBI patients (mortality 29.6%) of blood glucose (BG), base excess (BE), mean arterial pressure (MAP), PaO2/FiO2 ratio and serum hemoglobin (Hb). Predictive strength as the area under the receiver operating curves (AUROC) and correlation between all variables were calculated. RESULTS: Data are expressed as median, 1st-3rd quartile. Both BG AV (147.5, 126-182 mg/dL; AUROC 0.716, P=0.0002) and WV 48 h (156.5, 132-192 mg/dL; AUROC 0.721, P=0.0001) are predictive of mortality. AV and WV 48 h are respectively: PaO2/FiO2 (366.8, 237.2-477.6 vs. 320, 214.4-426; P=0.05), MAP (90, 80-100.5 vs. 75, 66-83 mmHg; P<0.0001) and Hb (11.4, 9.7-13.1 vs. 10.6, 9-12.2 g/dL; P<0.02). BG AV and WV 48 h correlates with: age (r=0.419, P<0.0001 and r=0.489, P<0.0001), PaO2/FiO2 AV (r -0.223, P<0.03 and r -0.236, P<0.02), PaO2/FiO2 WV 48 h (r -0.215, P<0.03 and r -0.279, P<0.005) and MAP WV 48 h (r -0.216, P<0.03 and r -0.261, P<0.007). CONCLUSION: Early hyperglycemia is a major predictor of mortality and correlates with other factors responsible for secondary injury. Early hyperglycemia seems to be a marker of inflammatory reaction responsible for early cardiovascular and respiratory impairment.

Changes in microvascular blood flow during coupled plasma filtration and adsorption.

A 51-year-old man with septic shock underwent three consecutive sessions of coupled plasma filtration-adsorption each lasting 12 hours. Sublingual microvascular perfusion was assessed using the orthogonal polarisation spectral imaging technique at three different times: immediate pre-coupled plasma filtration-adsorption phase, two hours following commencement and two hours after its termination. The video images of the sublingual microcirculation were analysed by an investigator blinded to the time of image acquisition. The De Backer's score was calculated. During the coupled plasma filtration-adsorption, the number of perfused vessels increased compared with the pre-coupled plasma filtration-adsorption period, but decreased again after its termination. It is arguable that the elimination of septic mediators during the procedure could account for the observed variations.

B-type natriuretic peptide as a predictor of outcome in a general intensive care unit.

BACKGROUND: B-type natriuretic peptide is a hormone secreted by the heart in response to ventricular wall stress. Increased B-type natriuretic peptide plasma levels are also found as a consequence of noncardiac conditions including sepsis, surgery-induced systemic inflammatory response syndrome and kidney failure. Since these conditions are common in general intensive care unit patients, we hypothesized that B-type natriuretic peptide could be a helpful marker in predicting outcome in this setting. METHODS: We measured plasma B-type natriuretic peptide concentrations in 228 patients at admission to our general intensive care unit. The primary aim of the study was to investigate the relationship between B-type natriuretic peptide and hospital mortality. The secondary aim of the study was to investigate the association between B-type natriuretic peptide and severity of disease, quantified by the Simplified Acute Physiology Score II. RESULTS: Logistic regression revealed a positive association between B-type natriuretic peptide level and in-hospital death (OR= 1.59; 95% CI 1.30 to 1.95; p<0.0001) and a Cox proportional hazards regression model showed that B-type natriuretic peptide was significantly associated with the risk of death (HR=1.27; 95% CI 1.11 to 1.46; p=0.0005). B-type natriuretic peptide was higher in patients who died in the hospital than in those who survived (371.20 pg/ml vs. 127.10 pg/ml; p<0.0001). There was a positive correlation between B-type natriuretic peptide and Simplified Acute Physiology Score II (r=0.50; 95% CI 0.40 to 0.59; p<0.0001). DISCUSSION: B-type natriuretic peptide on admission is an independent prognostic marker of outcome in an unselected cohort of critically ill patients.

The role of admission surveillance cultures in patients requiring prolonged mechanical ventilation in the intensive care unit.

We undertook a prospective observational cohort study in intensive care unit (ICU) patients requiring mechanical ventilation for four days or more to evaluate normal and abnormal bacterial carriage on admission detected by surveillance cultures of throat and rectum. We assessed the importance of surveillance and diagnostic cultures for the early detection of resistance to third generation cephalosporins employed as the parenteral component of the selective decontamination of the digestive tract. Finally, we sought the risk factors of abnormal carriage on admission to the ICU. During the 58-month study 621 patients were included: 186 patients (30%) carried abnormal flora including methicillin-resistant Staphylococcus aureus (MRSA) and aerobic Gram negative bacilli (AGNB) on admission to the ICU Both MRSA and AGNB carriers were more commonly present in the hospital group of patients than in patients referred from the community (P < 0.001), although overgrowth was equally present both in community and in hospital patients. The incidence of infections during ICU stay was higher in abnormal (n=120, 64.5%) than in normal carriers (n=185, 42.5%) (P < 0.0001), with an odds ratio of 2.46 (95% confidence interval 1.72 to 3.51). Third generation cephalosporins covered ICU admission flora in 482 (78%) of the studied population. AGNB resistant to cephalosporins and MRSA were detected in surveillance cultures of 139 patients (22%), while the same resistant micro-organisms were identified only in 49 diagnostic samples (7.9%). Parenteral cephalosporins were modified in patients with abnormal flora (P < 0.0001). One hundred and ninety-six patients received antibiotics before admission to the ICU and 42% carried AGNB resistant to cephalosporins. Previous antibiotic use was the only risk factor for abnormal carriage in the multivariate analysis (OR 3.5; 95% confidence interval 2.1 to 5.8). The knowledge of carriage on admission using surveillance cultures may help intensivists to identify patients with abnormal carriage on admission and resistant bacterial strains at an early stage even when diagnostic samples are negative. Third generation cephalosporins covered admission flora in about 80% of the enrolled population and were modified in patients with abnormal flora who received antibiotic therapy before ICU admission. Our finding of overgrowth present on admission may justify the immediate administration of enteral antimicrobials.

Early and prolonged ECG alterations resembling a myocardial injury after severe amitriptyline poisoning.

Evidence of cardiovascular toxicity is present in the majority of tricyclic antidepressant overdoses. We report the case of a 63-year-old woman admitted to our department with a severe amitriptyline poisoning. The ECG at admission showed a pattern mimicking an acute anteroseptal subepicardial infarction. This pattern persisted for 11 days. Myocardial enzymes and echocardiographic findings never confirmed an ischemic event. At discharge, the ECG returned normal without cardiac or neurologic sequelae. Our experience suggest that after severe tricyclic antidepressant ingestion, ECG alterations resembling myocardial injury may occur early and last for a longer period than previously reported.

Remifentanil to treat hypertension in overweight patients during a fentanyl-based cardiac anesthesia A case series.

Cardiac surgery is associated with intense nociceptive and autonomic stimulation especially during sternotomy and aortic root dissection and moderate-to-high dose opioids are required to blunt the hemodynamic and neuroendocrine response to this kind of procedures. However, episodes of unwanted sympathetic activation leading to intraoperative hypertension are not always preventable with a fentanyl-based anesthesia regimen and antihypertensive drugs without anesthetic properties are added to obtain hemodynamic stability. We report on five cardiac surgical cases in which intraoperative hypertension unresponsive to incremental doses of fentanyl was successfully treated adding a remifentanil target-controlled infusion instead of a non-anesthetic vasoactive drug. This approach could help to avoid the dilemma: when should we stop adding anesthetics and switch to antihypertensive drugs in cardiac surgery? 

Impact of selective decontamination of the digestive tract on carriage and infection due to Gram-negative and Gram-positive bacteria: a systematic review of randomised controlled trials.

Meta-analyses of randomised controlled trials of selective digestive decontamination have clinical outcome measures, mainly pneumonia and mortality. This meta-analysis has a microbiological endpoint and explores the impact of selective digestive decontamination on Gram-negative and Gram-positive carriage and severe infections. We searched electronic databases, Cochrane Register of Controlled Trials, previous meta-analyses and conference proceedings with no language restrictions. We included randomised controlled trials which compared the selective digestive decontamination protocol with no treatment or placebo. Three reviewers independently applied selection criteria, performed the quality assessment and extracted the data. The outcome measures were carriage and severe infection due to Gram-negative and Gram-positive bacteria. Odds ratios were pooled with the random effect model. Fifty-four randomised controlled trials comprising 9473 patients were included; 4672 patients received selective digestive decontamination and 4801 were controls. Selective digestive decontamination significantly reduced oropharyngeal carriage (odds ratio [OR] 0.13, 95% confidence interval [CI] 0.07 to 0.23), rectal carriage (OR 0.15, 95% CI 0.07 to 0.31), overall infection (OR 0.17, 95% CI 0.10 to 0.28), lower respiratory tract infection (OR 0.11, 95% CI 0.06 to 0.20) and bloodstream infection (OR 0.35, 95% CI 0.21 to 0.67) due to Gram-negative bacteria. Reduction in Gram-positive carriage was not significant. Gram-positive lower airway infections were significantly reduced (OR 0.52, 95% CI 0.34 to 0.78). Gram-positive bloodstream infections were not significantly increased (OR 1.03, 95% CI 0.75 to 1.41). The association of parenteral and enteral antimicrobials was superior to enteral antimicrobials in reducing carriage and severe infections due to Gram-negative bacteria. This meta-analysis confirms that selective digestive decontamination mainly targets Gram-negative bacteria; it does not show a significant increase in Gram-positive infection.

Prediction of successful defibrillation in human victims of out-of-hospital cardiac arrest: a retrospective electrocardiographic analysis.

In the present study we sought to examine the efficacy of an electrocardiographic parameter, 'amplitude spectrum area' (AMSA), to predict the likelihood that any one electrical shock would restore a perfusing rhythm during cardiopulmonary resuscitation in human victims of out-of-hospital cardiac arrest. AMSA analysis is not invalidated by artefacts produced by chest compression and thus it can be performed during CPR, avoiding detrimental interruptions of chest compression and ventilation. We hypothesised that a threshold value of AMSA could be identified as an indicator of successful defibrillation in human victims of cardiac arrest. Analysis was performed on a database of electrocardiographic records, representing lead 2 equivalent recordings from automated external defibrillators including 210 defibrillation attempts from 90 victims of out-of-hospital cardiac arrest. A 4.1 second interval of ventricular fibrillation or ventricular tachycardia, recorded immediately preceding the delivery of the shock, was analysed using the AMSA algorithm. AMSA represents a numerical value based on the sum of the magnitude of the weighted frequency spectrum between two and 48 Hz. AMSA values were significantly greater in successful defibrillation (restoration of a perfusing rhythm), compared to unsuccessful defibrillation (P < 0.0001). An AMSA value of 12 mV-Hz was able to predict the success of each defibrillation attempt with a sensitivity of 0.91 and a specificity of 0.97. In conclusion, AMSA analysis represents a clinically applicable method, which provides a real-time prediction of the success of defibrillation attempts. AMSA may minimise the delivery of futile and detrimental electrical shocks, reducing thereby post-resuscitation myocardial injury.

Mechanical loads modulate tidal volume and lung washout during high-frequency percussive ventilation.

High-frequency percussive ventilation (HFPV) has been proved useful in patients with acute respiratory distress syndrome. However, its physiological mechanisms are still poorly understood. The aim of this work is to evaluate the effects of mechanical loading on the tidal volume and lung washout during HFPV. For this purpose a single-compartment mechanical lung simulator, which allows the combination of three elastic and four resistive loads (E and R, respectively), underwent HFPV with constant ventilator settings. With increasing E and decreasing R the tidal volume/cumulative oscillated gas volume ratio fell, while the duration of end-inspiratory plateau/inspiratory time increased. Indeed, an inverse linear relationship was found between these two ratios. Peak and mean pressure in the model decreased linearly with increasing pulsatile volume, the latter to a lesser extent. In conclusion, elastic or resistive loading modulates the mechanical characteristics of the HFPV device but in such a way that washout volume and time allowed for diffusive ventilation vary agonistically.

Systemic and organ dysfunction response during infusion of recombinant human activated protein C (rhAPC) in severe sepsis and septic shock.

AIM: The aim of this study was the assessment of the efficacy of recombinant human activated protein C (rhAPC) in septic patients. METHODS: A continuous observational prospective study on ICU patients with severe sepsis and septic shock was carried out. Applying the inclusion criteria of a national trial on the use of rhAPC, 15 patients (12 males and 3 females) were enrolled, mean age was 65.9 (SD 9.6), APACHE II score was > or =25. The following variables were assessed on 7 time-points (T1-T7): overall SOFA score; organ-specific SOFA score; APACHE II score; PCR, APTT, INR, fibrinogen, platelet count. Wilcoxon's statistical test and Spearman's correlation test (rho coefficient) between the SOFA and APACHE II scores were used. Test results with a P value below 0.05 were deemed significant. RESULTS: A significant correlation was identified between the APACHE II and SOFA scores. No significant change was found in Friedman's test and the respiratory, haematological and hepatic SOFA score, whereas cardiovascular, renal and neurological SOFA scores showed a significant trend between the ranks at the 7 time-points (chi2=14; df=6; P=0.029). During rhAPC treatment Friedman's test showed significant changes of PCR values over the 7 time-points (chi2=19.2; df=6; P=0.02). Wilcoxon's test indicated a significant decrease in the values recorded during the T2-T6 period. On day 28, 12 of the 15 patients originally enrolled were still alive. Mortality rate was therefore 20% (CI 95%). CONCLUSIONS: RhAPC is the first biological agent approved for the treatment of severe sepsis and septic shock. Our experience is confined to patients with severe sepsis and septic shock, and some severity indexes showed a modulation of the inflammatory processes and haemostatic balance, 2 factors which play a key role in the evolution of sepsis and organ dysfunction.

Sepsis and organ dysfunction: an ongoing challenge.

In recent years the problem of infection has become increasingly significant, especially in intensive care hospital wards such as Intensive Care Units (ICU), emergency medicine, surgery and critically ill patient care departments. Sepsis is a complex, multifactorial syndrome that can develop into conditions of different severity, described as severe sepsis or septic shock. In these conditions the triggering event may coincide with the functional impairment of one or more vital organs or systems, thus leading to poorer prognosis in patients with overt signs of sepsis or systemic inflammation syndromes. The available data are quite alarming, as most prevention and treatment is performed empirically and requires considerable human and technological resources. Clinical signs are often misleading and, in some circumstances, it may be difficult or even impossible to identify the source of the infection which might otherwise be removed relatively simply, using proper antimicrobial treatment or a less invasive surgical removal of the area from which the infection originates based on needle-guided radiology. In addition, the complex pathophysiological mechanisms involved can be an obstacle to gaining a full understanding of the various biohumoral interactions or mediators action mechanisms. It may not be easy to enroll patients belonging to homogeneous groups in terms of age, underlining disease, immune profile or genetic predisposition, although the use of specific severity indexes has proved helpful also to establish the prognosis. Although the interpretation of generalised inflammation as a warning sign also in the absence of clear signs of infection or a state of overt inflammation has to rely largely on simple intuition, it has helped to drive experimental and clinical research work towards the investigation of interaction between different factors such as infection and sepsis, or inflammation and coagulation. An additional useful tool is the possibility of modulating the endothelial response which may support the process of disseminated thrombosis typical of sepsis evolution. In this context the improvement of standards of care can shed light on the efficacy of different treatments.

Control of imported and acquired methicillin-resistant Staphylococcus aureus (MRSA) in mechanically ventilated patients: a dose-response study of enteral vancomycin to reduce absolute carriage and infection.

This study aimed to quantify the animate source provided by the patients using the concept of "absolute carriage" by multiplying the carrier rate by the level of carriage; and to compare the impact of a low and high dose of an oropharyngeal vancomycin gel on the absolute MRSA carriage and infection. In all, 265 patients were included, 126 were MRSA positive. Fifty-five patients received 2% vancomycin gel during the first year whilst 4% vancomycin gel was given to 50 patients during the second year. Surveillance swabs of throat and rectum were obtained from all eligible patients on admission and then twice weekly. The vancomycin protocol was started as soon as the surveillance cultures were positive for MRSA. Those patients received one gram of enteral vancomycin daily, divided into four doses. During the first year 2% vancomycin gel 4 ml (80 mg) was applied in the oropharynx in four doses in addition to the enteral solution (Group A). During the second year 4% vancomycin gel 4 ml (160 mg) was used (Group B). The absolute carriage was high during both periods: 3.6 for Group A, and 3.2 for Group B. The 4% vancomycin protocol significantly reduced the absolute carriage, compared to the 2% vancomycin protocol: 2.6 versus 1.5 (P < 0.01). Significant reduction in secondary endogenous infections was found in the second year: seven versus 15 patients (P < 0.05). A total of 3,588 microbiological samples were processed. Neither Staphylococcus aureus with intermediate sensitivity to vancomycin (VISA) nor vancomycin-resistant enterococci (VRE) were detected.

Use of IgM and IgA-enriched immunoglobulins in the treatment of severe sepsis and septic shock. Clinical experience.

AIM: The aim of this study was to evaluate if the currently available clinical data and the time elapsing from the diagnosis to the administration of IgM and IgA-enriched immunoglobulins can predict the outcome of patients with severe sepsis and septic shock not responding to the current treatments. METHODS: All patients with these diagnoses, who did not respond to the standard treatment from August 1999 to September 2002, were retrospectively enrolled in the study. The variables evaluated included: (a) SAPS II and age at admission; (b) body temperature, mean arterial pressure, PaO2/FIO2 ratio, creatinine, blood white cell count on the day before the administration of the IgM and IgA-enriched immuno-globulins; (c) sequential organ failure assessment (SOFA) score before and during the treatment; (d) time elapsing between the diagnosis and the treatment; (e) outcome. RESULTS: Overall, 22 patients have been enrolled (17 M, 5 F, age 54.3+/-14.5 years). Eleven (50%) survived. None of the variables measured was different among survivors and nonsurvivors. Only the time elapsing from the diagnosis of severe sepsis and septic shock and the beginning of the treatment significantly differed among survivors and nonsurvivors (2.72 +/- 1.49 days vs 7.45 +/- 3.41 days respectively, p<0.005). CONCLUSION: In patients with severe sepsis and septic shock the currently available clinical variables and severity score are not valuable in identifying those patients who could take the maximal advantage from the administration of the IgM and IgA-enriched immunoglobulins. Thus, their time of administration plays a major role in the treatment of septic patients unresponding to the conventional treatment.

Cytomegalovirus endocarditis. A case report and a review of the literature.

The authors describe the case of a 75-year-old man admitted to our intensive care unit due to coma and respiratory failure; the history revealed a chronic renal failure due to an ANCA+ arteritis; subsequently, he developed a thrombotic thrombocytopenic purpura which was treated with plasma exchange. During his clinical course the patient developed polymicrobial and fungine sepsis and ultimately died. The autopsy demonstrated a severe cytomegalovirus endocarditis, which is extremely uncommon in non-immunodepressed patients as those receiving a solid-organ transplantation.

High frequency percussive ventilation (HFPV). Principles and technique.

In recent years, the usefulness of high frequency ventilation (HFV) has been clinically reassessed as an alternative to conventional mechanical ventilation (CMV). HFV has often been combined with or in some cases even completely replaced CMV in the attempt to reduce iatrogenic injury. High frequency percussive ventilation (HFPV) is a specific mode of HFV that has been successfully applied in the treatment of acute respiratory failure after smoke inhalation; it has also been more widely used in pediatric than in adult patients. This article gives an introduction to and a description of the basic principles of HFPV, a mode of ventilation which we found particularly versatile and reliable in our preliminary clinical experience with the maneuver.

High frequency percussive ventilation (HFPV). Case reports.

Treatment of acute respiratory failure is still a hot issue in intensive care everyday practice: in the last few years high frequency ventilation techniques have been employed as a therapy for adult respiratory distress syndrome (ARDS) and acute respiratory failure (ARF). We applied high frequency percussive ventilation (HFPV) to 3 patients affected by ARDS or ARF, who did not improve after 24 hours of conventional mechanical ventilation (CMV). All our patient underwent 12 hours of HFPV, and showed an improvement of both respiratory exchange and radiological imaging. Even if the pathogenesis of ARF was quite different, in all patient we registered a good response and no complications.

[Descending necrotizing mediastinitis. Clinical experience and review of the literature]. / La mediastiniti discendenti. Esperienza clinica e revisione della lettertaura.

The occurrence of a Descending Necrotizing Mediastinistis (DNM) usually is a consequence of oropharyngeal infections, which ultimately invade the mediastinum via the cervical fasciae. The clinical course is rapid and often fatal, and is associated with severe systemic symptoms, including fever and hypotension. In these cases, an aggressive surgical approach associated with an appropriate antibiotic treatment is mandatory. Personal experience in the treatment of DNM is presented and a review of the current literature is made; moreover an operative algorhythm is presented.