Abstract: PURPOSE: Pentraxin 3 (PTX3) is an inflammatory mediator produced by neutrophils, macrophages, myeloid dendritic and endothelial cells. During sepsis a massive inflammatory activation and coagulation/fibrinolysis dysfunction occur. PTX3, as a mediator of inflammation, may represent an early marker of severity and outcome in sepsis. METHODS: This study is based on a prospective trial regarding the impact of glycemic control on coagulation in sepsis. Ninety patients admitted to three general intensive care units were enrolled when severe sepsis or septic shock was diagnosed. At enrollment, we recorded sepsis signs, disease severity, coagulation activation [prothrombin fragments 1 + 2 (F(1+2))] and fibrinolysis inhibition [plasminogen activator inhibitor-1 (PAI-1)]. We measured plasma PTX3 levels at enrollment, everyday until day 7, then at days 9, 11, 13, 18, 23 and 28. Mortality was recorded at day 90. RESULTS: Although not different on day 1, PTX3 remained significantly higher in non-survivors than in survivors over the first 5 days (p = 0.002 by general linear model). On day 1, PTX3 levels were higher in septic shock than in severely septic patients (p = 0.029). Day 1 PTX3 was significantly correlated with platelet count (p < 0.001), SAPS II score (p = 0.006) and SOFA score (p < 0.001). Day 1 PTX3 was correlated with F(1+2) concentration and with PAI-1 activity and concentration (p < 0.05 for all). CONCLUSIONS: Persisting high levels of circulating PTX3 over the first days from sepsis onset may be associated with mortality. PTX3 correlates with severity of sepsis and with sepsis-associated coagulation/fibrinolysis dysfunction.
Abstract: BACKGROUND: Recent data suggest that during mechanical ventilation the lateral-horizontal patient position (in which the endotracheal tube is horizontal) decreases the risk of ventilator-associated pneumonia, compared to the recommended semi-recumbent position (in which the endotracheal tube slopes downward into the trachea). We tested the feasibility of the lateral-horizontal patient position, measured the incidence of aspiration of gastric contents, and watched for any adverse effects related to the lateral-horizontal position. METHODS: Ten adult intensive care unit patients were ventilated for 64 hours in the standard semi-recumbent position, and ten for 12-24 hours in the lateral-horizontal position. Tracheal secretions were collected every 8 hours and every 4 hours, respectively, and tested for pepsin, which is a marker of gastric contents. We also recorded clinical, physiologic, and outcome variables. RESULTS: The patients remained stable during ventilation in the lateral-horizontal position, and no adverse events occurred. Pepsin was detected in the trachea of 7 semi-recumbent patients and in five of the lateral-horizontal patients (P = .32). The number of ventilator-free days was 8 days (range 0-21 days) in the semi-recumbent patients, versus 24 days (range 12-25 days) in the lateral-horizontal patients (P = .04). CONCLUSIONS: Implementing the lateral-horizontal position for 12-24 hours in adult intubated intensive care unit patients is feasible, and our patients had no adverse events. The incidence of aspiration of gastric contents in the lateral-horizontal position seems to be similar to that in the semi-recumbent position.
Abstract: AIM: The outcomes of patients affected by hematologic malignancies (HM) admitted to Intensive Care Units (ICUs) because of life-threatening complications are still considered to be poor. The aim of this study was to assess the incidence and impact of cardiac dysfunction on the outcome of these patients. METHODS: We retrospectively reviewed the records of the 48 patients (both adult and pediatric) with HM admitted in our ICU over the last four years, collecting data on admission diagnosis, type of HM, laboratory values and organ failure. RESULTS: All patients were admitted with respiratory failure. The overall mortality rate was 50% and the mortality rates were similar among patients with different types of HM. Septic shock and multiple organ failure were the leading causes of death. The overall incidence of cardiac dysfunction was high (31%). Interestingly, the ICU mortality of this subgroup was 27%, while the mortality of the rest of the population was 61% (p<0.05). CONCLUSIONS: ICU patients with HM have high mortality. Respiratory failure caused by cardiac dysfunction seems to be associated with a lower risk of death.
Abstract: BACKGROUND: Prone position ventilation for acute hypoxemic respiratory failure (AHRF) improves oxygenation but not survival, except possibly when AHRF is severe. OBJECTIVE: To determine effects of prone versus supine ventilation in AHRF and severe hypoxemia [partial pressure of arterial oxygen (PaO(2))/inspired fraction of oxygen (FiO(2)) <100 mmHg] compared with moderate hypoxemia (100 mmHg </= PaO(2)/FiO(2) </= 300 mmHg). DESIGN: Systematic review and meta-analysis. DATA SOURCES: Electronic databases (to November 2009) and conference proceedings. METHODS: Two authors independently selected and extracted data from parallel-group randomized controlled trials comparing prone with supine ventilation in mechanically ventilated adults or children with AHRF. Trialists provided subgroup data. The primary outcome was hospital mortality in patients with AHRF and PaO(2)/FiO(2) <100 mmHg. Meta-analyses used study-level random-effects models. RESULTS: Ten trials (N = 1,867 patients) met inclusion criteria; most patients had acute lung injury. Methodological quality was relatively high. Prone ventilation reduced mortality in patients with PaO(2)/FiO(2) <100 mmHg [risk ratio (RR) 0.84, 95% confidence interval (CI) 0.74-0.96; p = 0.01; seven trials, N = 555] but not in patients with PaO(2)/FiO(2) >/=100 mmHg (RR 1.07, 95% CI 0.93-1.22; p = 0.36; seven trials, N = 1,169). Risk ratios differed significantly between subgroups (interaction p = 0.012). Post hoc analysis demonstrated statistically significant improved mortality in the more hypoxemic subgroup and significant differences between subgroups using a range of PaO(2)/FiO(2) thresholds up to approximately 140 mmHg. Prone ventilation improved oxygenation by 27-39% over the first 3 days of therapy but increased the risks of pressure ulcers (RR 1.29, 95% CI 1.16-1.44), endotracheal tube obstruction (RR 1.58, 95% CI 1.24-2.01), and chest tube dislodgement (RR 3.14, 95% CI 1.02-9.69). There was no statistical between-trial heterogeneity for most clinical outcomes. CONCLUSIONS: Prone ventilation reduces mortality in patients with severe hypoxemia. Given associated risks, this approach should not be routine in all patients with AHRF, but may be considered for severely hypoxemic patients.
Abstract: PURPOSE OF REVIEW: We report on the evolution of airway pressure and flow monitoring from a pathophysiological tool to the cornerstone of ventilator-induced lung injury (VILI) prevention. RECENT FINDINGS: Protective ventilatory strategies are based on reduction of volume and pressures delivered to the lungs. New evidence, which will need confirmation in further studies, suggests that transpulmonary pressure (alveolar pressure minus pleural pressure), could be used to titrate both the positive end-expiratory pressure (PEEP) level and the inspiratory pressure applied by the ventilator. A limited number of animal studies are strongly supporting a role for inspiratory flow on the development of VILI.Moreover, different airway flow patterns may affect secretion movement, both global, to the alveoli or the glottis, and regional, from lower to higher compliance regions. This intra-lung transfer may be a primary mechanism for the propagation of infections and inflammatory mediators.Alternative monitoring techniques (among others) are the rapid interrupter technique, which can be used to measure airway resistance and patients' inspiratory effort and the forced oscillation technique which could become a bedside technique to estimate recruitment/derecruitment and titrate PEEP. SUMMARY: Airway pressure and flow monitoring is essential for VILI prevention and for an appropriate setting of mechanical ventilation.
Abstract: PURPOSE OF REVIEW: We report on recent advances and achievements on the use of extracorporeal gas exchange for long-term application in the therapy of critically ill patients with various forms of respiratory failure. RECENT FINDINGS: The most important results regarding the use of extracorporeal gas exchange are expected from the Conventional Ventilatory Support vs. Extracorporeal Membrane Oxygenation for Severe Adult Respiratory Failure (CESAR) study, a randomized clinical trial assessing the effectiveness of extracorporeal lung assist in acute respiratory distress syndrome patients. Although not yet formally published, the results of this study, if confirmed, represent the first positive randomized clinical trial on adult extracorporeal membrane oxygenation application in acute respiratory distress syndrome patients. Other important results come from the clinical application of interventional lung assist, a pumpless arteriovenous extracorporeal technique, in different clinical conditions (acute respiratory distress syndrome, bridge to transplantation, asthma, and trauma). Among technical progress, of particular interest is the development of microfiber, microporous polymethylpentene membrane lungs, which offer low resistance to blood flow, high gas transfer capability, and high leak-proof performance. SUMMARY: Results of recent clinical trials, widespread use of clinical applications, and technical progress are leading to reevaluation and extension of extracorporeal gas exchange in critically ill patients with respiratory failure of various forms. Further developments may come from low invasive techniques with high efficiency of CO2 removal from low blood flow.
Abstract: PURPOSE: Assessing feasibility and physiological effects of sedation with sevoflurane, administered with the anesthetic conserving device (AnaConDa), in comparison with propofol and remifentanil. METHODS: Seventeen patients undergoing mechanical ventilation underwent sedation with sevoflurane delivered with AnaConDa (phase SevAn), preceded and followed by sedation with propofol and remifentanil (phases ProRe(1), ProRe(2)), with the same sedation targets. RESULTS: With both strategies it was possible to achieve the sedation targets. Time required to sedate and awake patients was greater during SevAn than ProRe(1): respectively, 3.3 +/- 3.0 versus 8.9 +/- 6.1 and 7.47 +/- 5.05 versus 16.3 +/- 11.4 min. During SevAn the PaCO(2) and minute ventilation increased. Hemodynamics was stable between ProRe(1) and SevAn, except for an increase in heart rate in the SevAn phase. Environmental pollution from sevoflurane was within the safety limits. CONCLUSIONS: Sevoflurane can be effectively and safely used for short-term sedation of ICU patients with stable hemodynamic conditions.
Abstract: PURPOSE: The purpose of this study is to describe and test a modified Boussignac system for non-invasive continuous positive airway pressure, aimed at reducing the decrease in inspiratory oxygen fraction (FiO(2)) with higher inspiratory peak flow rates. METHODS: We modified a Boussignac circuit by inserting a T-piece between the Boussignac valve and the face mask. The T-piece was connected to a reservoir balloon receiving oxygen by an independent source. The system was tested in a bench study, consisting of five steps, with increasing inspiratory peak flow rates (V(insp)) Three levels of PEEP were tested: 7, 10 and 13 cmH(2)O. The following devices were tested: Boussignac, Boussignac with reservoir but without supplementary oxygen, Boussignac with reservoir and 10 (SUPER-Boussignac(10)) and 30 l/min (SUPER-Boussignac(30)) of supplementary oxygen. In each step we measured FiO(2), tidal volumes, and airway pressure. RESULTS: FiO(2) increased with PEEP and decreased at increasing V(insp) with all the systems. However, FiO(2) increased with SUPER-Boussignac(10) (7-10%) and with SUPER-Boussignac(30) (10-30%). Moreover, in the latter case, for V(insp) values up to 60 l/min, FiO(2) became independent of V(insp). The SUPER-Boussignac allowed also smaller drop in airway pressure during inspiration and higher tidal volumes. CONCLUSIONS: The SUPER-Boussignac represents a simple way to significantly improve the performance of the Boussignac device.
Abstract: AIM: Recombinant human activated protein C (rh-APC) and tight glycemic control (TGC) have been shown to reduce mortality in septic patients. Both interventions can reduce the plasma concentration and/or activity of the most powerful suppressor of fibrinolysis, plasminogen activator inhibitor-1 (PAI-1). Our aim was to evaluate the effects on the fibrinolytic system after the administration of rh-APC in septic patients undergoing conventional or TGC. METHODS: Posthoc analysis of data was collected from 90 patients with severe sepsis/septic shock, randomized to either conventional or TGC groups. Independent of these treatments, patients with at least two organ dysfunctions simultaneously received rh-APC. Plasma levels of multiple biochemical markers for fibrinolysis, coagulation, and inflammation were determined every day for the 1st week and then on study days 9, 11, 13, 18, 23, and 28. Clinical data and sepsis-related organ failure assessment (SOFA) scores were also recorded. RESULTS: Patients who had received rh-APC exhibited significantly more impairments in fibrinolysis at baseline (PAI-1 activity 49.76 [24.61-71.82] vs 21.92 [6.47-55-83] IU/mL, P=0.03). The reductions in plasma PAI-1 activity over time associated with rh-APC treatment were different according to whether the treatment was administered to patients undergoing conventional or TGC (P=0.01). However, the most prominent reductions were in patients undergoing conventional glycemic control. Significant interactions between the two study interventions were also found for PAI-1 concentration (P<0.001), C-reactive protein (P=0.02), and interleukin-6 levels (P<0.001). CONCLUSIONS: Both rh-APC and TGC appear to improve fibrinolysis in septic patients. The reduction in the impairment of fibrinolysis associated with rh-APC treatment seems greater in patients undergoing conventional glycemic control than in those undergoing TGC.
Abstract: BACKGROUND: Many studies have attempted to determine the "best" anaesthetic technique for neurosurgical procedures in patients without intracranial hypertension. So far, no study comparing intravenous (IA) with volatile-based neuroanaesthesia (VA) has been able to demonstrate major outcome differences nor a superiority of one of the two strategies in patients undergoing elective supratentorial neurosurgery. Therefore, current practice varies and includes the use of either volatile or intravenous anaesthetics in addition to narcotics. Actually the choice of the anaesthesiological strategy depends only on the anaesthetists' preferences or institutional policies. This trial, named NeuroMorfeo, aims to assess the equivalence between volatile and intravenous anaesthetics for neurosurgical procedures. METHODS/DESIGN: NeuroMorfeo is a multicenter, randomized, open label, controlled trial, based on an equivalence design. Patients aged between 18 and 75 years, scheduled for elective craniotomy for supratentorial lesion without signs of intracranial hypertension, in good physical state (ASA I-III) and Glasgow Coma Scale (GCS) equal to 15, are randomly assigned to one of three anaesthesiological strategies (two VA arms, sevoflurane + fentanyl or sevoflurane + remifentanil, and one IA, propofol + remifentanil). The equivalence between intravenous and volatile-based neuroanaesthesia will be evaluated by comparing the intervals required to reach, after anaesthesia discontinuation, a modified Aldrete score > or = 9 (primary end-point). Two statistical comparisons have been planned: 1) sevoflurane + fentanyl vs. propofol + remifentanil; 2) sevoflurane + remifentanil vs. propofol + remifentanil. Secondary end-points include: an assessment of neurovegetative stress based on (a) measurement of urinary catecholamines and plasma and urinary cortisol and (b) estimate of sympathetic/parasympathetic balance by power spectrum analyses of electrocardiographic tracings recorded during anaesthesia; intraoperative adverse events; evaluation of surgical field; postoperative adverse events; patient's satisfaction and analysis of costs. 411 patients will be recruited in 14 Italian centers during an 18-month period. DISCUSSION: We presented the development phase of this anaesthesiological on-going trial. The recruitment started December 4th, 2007 and up to 4th, December 2008, 314 patients have been enrolled.
Abstract: PURPOSE: Non-invasive continuous positive airway pressure (CPAP) is effective in reducing intubation rate and mortality of patient with acute cardiogenic pulmonary edema (ACPE). We report our experience on pre-hospital application of CPAP by helmet as an adjunct to medical therapy or as a stand alone procedure in patient with presumed ACPE. METHODS: In pre-hospital treatment of 62 patients with presumed ACPE, CPAP was added to standard medical treatment while in another 59 patients, CPAP was used as a sole therapy. RESULTS: Helmet CPAP was feasible in all patients. No patient required pre-hospital intubation. In both groups, CPAP significantly improved oxygenation (SpO(2) went from 79 +/- 12 to 97 +/- 3% and from 81 +/- 13 to 98 +/- 3%), reduced respiratory rate (from 26 +/- 4 to 21 +/- 3 bpm and from 30 +/- 9 to 22 +/- 8 bpm) and improved hemodynamics, with a more pronounced decrease in blood pressure in the group with medical treatment than in the one without it. In the two cohorts, four and five patients were, respectively, intubated in Emergency Department and 11 and 9 eventually died. CONCLUSIONS: Helmet CPAP is feasible, efficient and safe in pre-hospital treatment of presumed ACPE. A significant improvement of physiological variables was observed also in the group treated with CPAP in the absence of a drug therapy. We propose helmet CPAP as first line pre-hospital treatment of presumed severe ACPE.
Abstract: OBJECTIVE: To investigate whether tight glycemic control, in patients with sepsis, may restore a normal fibrinolysis by lowering plasminogen activator inhibitor (PAI)-1 levels. DESIGN: Prospective randomized clinical trial. SETTING: Three Italian university hospital intensive care units. PATIENTS: Ninety patients with severe sepsis/septic shock. INTERVENTIONS: Patients were randomized to receive either tight glycemic control (treatment group, target glycemia, 80-110 mg/dL) or conventional glycemic control (control group, target glycemia, 180-200 mg/dL). MEASUREMENTS: Inflammation, coagulation, and fibrinolysis markers were assessed, along with Sepsis-related Organ Failure Assessment scores, >28 days. MAIN RESULTS: In the whole population, at enrolment, inflammation and coagulation were activated in >80 of 90 patients, whereas fibrinolysis, as assessed by PAI-1 activity and concentration, was impaired in only 34 patients. The extent of the inflammatory reaction or of the coagulation activation was unrelated to outcome. In contrast, 90-day mortality rate of the 34 patients in whom fibrinolysis was definitely inhibited at study entry was twice that of the 56 patients in whom fibrinolysis was intact (44% vs. 21%, p = 0.02). After randomization, during the study, daily glycemia averaged 112 +/- 23 mg/dL in the treatment group and 159 +/- 31 mg/dL in controls (p < 0.001), with total daily administered insulin 57 +/- 59 IU and 36 +/- 44 IU, respectively (p < 0.001). A small, but significant, enhancement of fibrinolysis could be observed in the treatment group, as indicated by the time course of PAI-1 activity (p < 0.001), PAI-1 concentration (p = 0.004), and plasmin-antiplasmin complexes (p < 0.001). Morbidity, rated with the Sepsis-related Organ Failure Assessment score, became significantly lower (p = 0.03) in the treatment group. CONCLUSIONS: Fibrinolysis inhibition, in severe sepsis/septic shock, seems to have a relevant pathogenetic role. In this context, tight glycemic control seems to reduce, with time, the fibrinolytic impairment and morbidity.
Abstract: CONTEXT: Post hoc analysis of a previous trial has suggested that prone positioning may improve survival in patients with severe hypoxemia and with acute respiratory distress syndrome (ARDS). OBJECTIVE: To assess possible outcome benefits of prone positioning in patients with moderate and severe hypoxemia who are affected by ARDS. DESIGN, SETTING, AND PATIENTS: The Prone-Supine II Study, a multicenter, unblinded, randomized controlled trial conducted in 23 centers in Italy and 2 in Spain. Patients were 342 adults with ARDS receiving mechanical ventilation, enrolled from February 2004 through June 2008 and prospectively stratified into subgroups with moderate (n = 192) and severe (n = 150) hypoxemia. INTERVENTIONS: Patients were randomized to undergo supine (n = 174) or prone (20 hours per day; n = 168) positioning during ventilation. MAIN OUTCOME MEASURES: The primary outcome was 28-day all-cause mortality. Secondary outcomes were 6-month mortality and mortality at intensive care unit discharge, organ dysfunctions, and the complication rate related to prone positioning. RESULTS: Prone and supine patients from the entire study population had similar 28-day (31.0% vs 32.8%; relative risk [RR], 0.97; 95% confidence interval [CI], 0.84-1.13; P = .72) and 6-month (47.0% vs 52.3%; RR, 0.90; 95% CI, 0.73-1.11; P = .33) mortality rates, despite significantly higher complication rates in the prone group. Outcomes were also similar for patients with moderate hypoxemia in the prone and supine groups at 28 days (25.5% vs 22.5%; RR, 1.04; 95% CI, 0.89-1.22; P = .62) and at 6 months (42.6% vs 43.9%; RR, 0.98; 95% CI, 0.76-1.25; P = .85). The 28-day mortality of patients with severe hypoxemia was 37.8% in the prone and 46.1% in the supine group (RR, 0.87; 95% CI, 0.66-1.14; P = .31), while their 6-month mortality was 52.7% and 63.2%, respectively (RR, 0.78; 95% CI, 0.53-1.14; P = .19). CONCLUSION: Data from this study indicate that prone positioning does not provide significant survival benefit in patients with ARDS or in subgroups of patients with moderate and severe hypoxemia. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00159939.
Abstract: AIM: The aim of this study was to investigate the hypothesis that periodical sampling of the tracheo-bronchial tree in the absence of clinical suspicion of pneumonia is useful to identify bacteria responsible for subsequent late ventilator associated pneumonia (VAP). This was a retrospective observational human study carried out in two medical-surgical intensive care units of two different hospitals. From January 1999 to December 2000, 559 patients, who received invasive respiratory support for more than 48 hours, were screened. METHODS: Tracheal aspiration (TA) was performed once or twice weekly in all mechanically ventilated patients. The microbiological findings from TA surveillance cultures done in the eight days before suspicion of VAP were compared to those isolated from the positive diagnostic samples done for late onset VAP (after more than four days of mechanical ventilation). The sensitivity, specificity, and positive/negative predictive values of the ability of the surveillance sample to anticipate the VAP pathogen were calculated. RESULTS: Among the microorganisms isolated from TA, 68% were retrieved from diagnostic samples. All VAP pathogens previously isolated were from 43% of the TA samples. If TA was collected 2-4 days before the clinical diagnosis of VAP, pathogens were detected in 58% of samples. In contrast, only 27% were collected more than four days earlier (P<0.05). The positive predictive values for Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus from routine TA samples were 92% and 90%, respectively. The negative predictive values for Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus from routine TA samples were 75% and 89%, respectively. CONCLUSIONS: TA cultures in ventilated patients may help to predict pathogens. Early detection may lead to earlier treatment in long term ventilated patients when VAP is suspected.
Abstract: After the first outbreak identified in Mexico in late March 2009, influenza A sustained by a modified H1N1 virus ("swine flu") rapidly spread to all continents. This article describes the first Italian case of life-threatening ARDS associated with H1N1 infection, treated with extracorporeal respiratory assistance (venovenous extracorporeal membrane oxygenation [ECMO]). A 24-year-old, previously healthy man was admitted to the Intensive Care Unit (ICU) of the local hospital for rapidly progressive respiratory failure with refractory impairment of gas exchange unresponsive to rescue therapies (recruitment manoeuvres, pronation and nitric oxide inhalation). An extracorporeal respiratory assistance (venovenous ECMO) was performed. It allowed a correction of the respiratory acidosis and made possible the transportation of the patient to the ICU (approximately 150 km from the first hospital). A nasal swab tested positive for H1N1 infection and treatment with oseltamivir was started. The chest computed tomography scan showed bilateral massive, patchy consolidation of lung parenchyma; lab tests showed leukopenia, elevated CPK levels and renal failure. The patient required high dosages of norepinephrine for septic shock and continuous renal replacement therapy. The clinical course was complicated by Pseudomonas aeruginosa superinfection, treated with intravenous and aerosolised colistin. ECMO was withheld after 15 days, while recovery of renal and respiratory function was slower. The patient was discharged from the ICU 34 days after admission. In this case, ECMO was life-saving and made the inter-hospital transfer of the patient possible.
Abstract: OBJECTIVE:: To demonstrate the technical feasibility of CO2 removal with a commercial hemofilter and a replacement solution containing sodium hydroxide to replace bicarbonate. DESIGN:: Prospective animal experiment in sheep. SUBJECTS:: Seven mixed-breed female sheep. INTERVENTIONS:: Blood ultrafiltrate containing half of the metabolic production of CO2 was removed with a commercial hemofilter and a replacement solution containing sodium hydroxide was given as replacement. Minute ventilation was lowered to less than half of its baseline value. Ultrafiltration was stopped at 18 hrs, and Paco2 was allowed to increase for about 1 hr; at this time, the sheep were electively killed. MEASUREMENTS AND MAIN RESULTS:: Every 6 hrs, blood was sampled from the carotid artery, the pulmonary artery, and from the extracorporeal perfusion circuit (before the hemofilter, immediately after the hemofilter, and after mixing with the replacement solution). To maintain normocapnia, minute ventilation was reduced from 3.8 +/- 0.1 L/min to 1.9 +/- 0.7 L/min; Paco2 remained near constant during the study. The average blood pH, after mixing with the replacement solution, was 7.64 +/- 0.12. One hour after the ultrafiltration had stopped, Paco2 had increased from 36.7 +/- 4.2 torr (4.9 +/- 0.6 kPa) to 59.6 +/- 9 torr (7.9 +/- 1.2 kPa) (p < .01) and blood pH had decreased from 7.317 +/- 0.041 to 7.151 +/- 0.051 (p < .01). CONCLUSION:: CO2 removal with bicarbonate ultrafiltration may be an effective treatment for patients with respiratory failure.
Abstract: PURPOSE: Extracorporeal CO2 removal is an effective procedure to allow a protective ventilatory strategy in ARDS patients, but it is technically challenging due to the high blood flow required. Increasing the CO2 transfer through the membrane lung (ML) may lower the demand of extracorporeal blood flow and consequently allow for a wider clinical application of this technique. Since only the dissolved CO2 (5% of the total CO2 content) is easily removed by the ML, we tested whether acidifying the blood entering the ML to convert bicarbonate ions towards dissolved CO2 could enhance the CO2 transfer though the ML. METHODS: Six pigs were connected to an extracorporeal circuit comprising a ML. The extracorporeal blood flow was 500 ml/min, while the gas flow was 10 l/min. A 15-min continuous infusion of 0.5 N lactic acid was added to the extracorporeal blood flow before the ML at a rate of 1, 2 and 5 mEq/min. Between steps we waited for a reequilibration time of at least 30 min. RESULTS: Acid infusion at 0, 1, 2 and 5 mEq/min increased pCO2 (56.19 +/- 7.92, 68.24 +/- 11.73, 84.28 +/- 11.17 and 136.66 +/- 18.46 mmHg, respectively) and decreased pH (7.39 +/- 0.05, 7.30 +/- 0.05, 7.20 +/- 0.05 and 6.91 +/- 0.05, respectively). ML CO2 removal increased 11, 23 and 70% during acid infusion at 1, 2 and 5 mEq/min, respectively. CONCLUSIONS: Blood acidification at the inlet of a ML with infusion of 1, 2 and 5 mEq/min of lactic acid can increase the CO2 removal capacity of the ML up to 70%.
Abstract: OBJECTIVE: Neutrophilic inflammation plays a key role in the pathogenesis of acute respiratory distress syndrome (ARDS) and acute lung injury (ALI). Positron emission tomography (PET) with [F]-fluoro-2-deoxy-D-glucose (FDG) can be used to image cellular metabolism that, during lung inflammatory processes, likely reflects neutrophils activity. The aim of this study was to assess the magnitude and regional distribution of inflammatory metabolic activity in the lungs of patients with ALI/ARDS by PET with FDG. DESIGN: Prospective clinical investigation. PATIENTS: Ten patients with ALI/ARDS; four spontaneously breathing and two mechanically ventilated subjects, without known lung disease, served as controls. INTERVENTIONS: In each individual we performed an FDG PET/computed tomography of the thorax. MEASUREMENTS AND MAIN RESULTS: FDG cellular influx rate constant (Ki) was computed for the imaged lung field and for regions of interest, grouping voxels with similar density. In all patients with ALI/ARDS, Ki was higher than in controls, also after accounting for the increased lung density. Ki values differed greatly among patients, but in all patients Ki of the normally aerated regions was much higher (2- to 24-fold) than in controls. Whereas in some patients the highest Ki values corresponded to regions with the lowest aeration, in others these regions had lower Ki than normally and mildly hypoaerated regions. CONCLUSION: In patients with ALI/ARDS, undergoing mechanical ventilation since days, the metabolic activity of the lungs is markedly increased across the entire lung density spectrum. The intensity of this activation and its regional distribution, however, vary widely within and between patients.
Abstract: OBJECTIVE: Coated medical devices have been shown to reduce catheter-related infections. We coated endotracheal tubes (ETT) with silver sulfadiazine (SSD), and tested them in a clinical study to assess the feasibility, safety, and efficacy of preventing bacterial colonization. DESIGN: A prospective, randomized clinical trial, phase I-II. SETTING: Academic intensive care unit (ICU). PARTICIPANTS: Forty-six adult patients expected to need 12-24 h of intubation were randomized into two groups. INTERVENTIONS: Patients were randomized to be intubated with a standard non-coated ETT (St-ETT, n=23; control group), or with a SSD-coated ETT (SSD-ETT, n=23). MEASUREMENTS AND RESULTS: Coating with SSD prevented bacterial colonization of the ETT (frequency of colonization: SSD-ETT 0/23, St-ETT 8/23; p<0.01). No organized bacterial biofilm could be identified on the lumen of any ETT; however, SSD was associated with a thinner mucus layer (in the SSD-ETT secretion deposits ranged from 0 to 200 microm; in the St-ETT deposits ranged between 50 and 700 microm). No difference was observed between the two groups in the tracheobronchial brush samples (frequency of colonization: SSD-ETT 0/23, St-ETT 2/23; p=0.48). No adverse reactions were observed with the implementation of the novel device. CONCLUSION: SSD-ETT can be safely used in preventing bacterial colonization and narrowing of the ETT in patients intubated for up to 24 h (mean intubation time 16 h).
Abstract: Although microporous polypropylene hollow fiber oxygenators are standard devices used for extracorporeal membrane oxygenation (ECMO), they have limitations such as development of plasma leakage. Poly-methylpentene (PMP) is a new material used for the last generation of oxygenators. We reviewed our experience with a new PMP oxygenator (Quadrox D) and a centrifugal pump (RotaFlow) used to support adult patients with refractory cardiogenic shock. Between January 2000 and April 2007, 25 patients required ECMO for primary or postcardiotomy cardiogenic shock. Eighteen patients were analyzed [mean age 60.2 years; 11 (61%) men; 7 (39%) women]. Nine patients (50%) suffered primary cardiogenic shock. Cardiopulmonary resuscitation was applied in 11 patients (61%) with a mean duration time of 31.5 minutes. Mean ECMO duration time was 7.1 +/- 6.3 days (range, 1-27 days). Intra-aortic balloon pump was used in 13 patients (72.2%) with a mean duration time of 7.7 +/- 5 (range, 2-17 days). Twelve patients (66.7%) survived on ECMO and five patients (27.8%) were discharged. Our results indicate the PMP oxygenator and the centrifugal pump provided acceptable results in terms of surviving on ECMO and discharge. Patients with an initial catastrophic hemodynamic status could benefit by means of a rapid institution of ECMO with PMP oxygenators.
Abstract: BACKGROUND: Acid aspiration is a complication of general anesthesia. Most animal models developed to define its pathophysiology have focused on the acute (< or =24 h) phase of the injury. The authors describe a model of acid aspiration allowing the study of this type of lung injury over time. METHODS: The authors instilled hydrochloric acid (0.1 m, 1.5 ml/kg) or normal saline in the right bronchus of mice. Lung injury was evaluated at 6 h, 12 h, 24 h, and 2 weeks by assessing arterial blood gases, respiratory system compliance, lung wet weight normalized by body weight, lung myeloperoxidase activity, and histology. Twelve hours and 2 weeks after injury, a computed tomography scan was obtained. RESULTS: In the hydrochloric acid group, arterial oxygen tension decreased (P < 0.05) at 12 and 24 h, whereas it recovered at 2 weeks; respiratory system compliance was lower both at 24 h and 2 weeks (P < 0.05). Lung weight increased at 12 and 24 h (P < 0.05). Myeloperoxidase activity peaked between 6 and 12 h. Computed tomography at 12 h showed that almost 30% of the injured lung was abnormally aerated. Although reduced, the abnormalities were still present at 2 weeks as confirmed by a fibrotic scar well evident at histologic examination. CONCLUSION: The authors characterized a murine model of regional acid aspiration allowing long-term survival. Despite a partial recovery, at 2 weeks the injury persisted, with evidence of fibrosis and lung compliance reduction. This long-term, low-mortality model seems suitable for assessment of the effects of different therapies on lung injury and repair.
Abstract: Non-invasive continuous positive airway pressure (CPAP) is a useful tool for managing patients with acute respiratory failure. The head helmet is a relatively novel interface that is as effective as the traditionally employed face-mask in delivering CPAP and can possibly be characterized as better for the patient's tolerance and, consequently, a longer duration of treatment. This review focuses on the main properties of the helmet and the issues related to its use, as shown by the physiological and bench studies. Clinical experience, both personal and reported in the literature, for the treatment of both cardiogenic and non-cardiogenic pulmonary edema is reviewed as well.
Abstract: OBJECTIVE: We investigated whether preventing hyperglycemia in septic patients affected the plasma concentration of asymmetric-dimethylarginine and if this was associated with clinical benefit. DESIGN: A prospective, multicenter, randomized, controlled, clinical study. SETTING: Intensive care units (ICU) in three university hospitals. PATIENTS: A total of 72 patients admitted for severe sepsis or septic shock, who stayed at least 3 days in the ICU. At admission the patients were assigned to receive either tight or conventional glycemic control. INTERVENTIONS: Determination of circulating levels of asymmetric-dimethylarginine, arginine, interleukin-6, C-reactive-protein and tumor-necrosis-factor-alpha. MEASUREMENTS AND RESULTS: Blood was sampled at admission (no differences between groups), and on the 3rd, 6th, 9th, and 12th (T12) days. Sequential organ failure assessment was scored at each sampling time. All the data were analyzed on an intention-to-treat basis. The control and treatment groups received the same energy intake, glycemia (110.4 +/- 17.3 vs. 163.0 +/- 28.9 mg/dL, P < 0.001) and insulin (P = 0.02) supply differed. No differences were found in high plasma levels of asymmetric-dimethylarginine (P = 0.812) at any time during the ICU stay. The clinical course, as indicated by markers of inflammation, average and maximum organ failure score, ICU stay and ICU and 90-day mortality, was the same. CONCLUSIONS: Intensive insulin treatment, while achieving glucose control, did not reduce asymmetric-dimethylarginine in high-risk septic patients fed with no more than 25 kcal/kg per day to limit ventilatory demand and to simplify glucose control. DESCRIPTOR: 45 (SIRS/sepsis: clinical studies).
Abstract: Intubation is necessary in 7 to 20% of patients with severe acute cardiogenic pulmonary oedema despite optimal treatment. This study evaluated the usefulness of parameters largely available in clinical practice to predict the need for intubation in a population of acute cardiogenic pulmonary oedema patients treated with medical therapy and continuous positive airway pressure. The present retrospective cohort study involved 142 patients with severe acute cardiogenic pulmonary oedema who were admitted to coronary care or the intensive care unit of a university hospital and were treated by an in-hospital protocol. Physiological measurements and blood gas samples were evaluated at 'baseline' (just after admission), 'early' (one to three hours after beginning treatment) and 'late' (eight to 10 hours after beginning treatment). Twenty-two patients (15.5%) required intubation. A systolic blood pressure at admission lower than 140 mmHg was significantly associated with a higher risk for intubation, while hypercapnic patients or those with a reduced left ventricular ejection fraction at admission did not show a worse prognosis. A simple score based on largely available parameters (1 point for each: age >78 years, systolic blood pressure <140 mmHg at admission, arterial blood gas acidosis and heart rate >95 bpm at early time) is proposed. The rate of intubation according to this score ranged from 0% (score of 0) to 90% (score of 3). Our study found that simple parameters available in clinical practice are significantly associated with the need for intubation in acute cardiogenic pulmonary oedema patients treated with continuous positive airway pressure and medical therapy. A simple score to evaluate the need for endotracheal intubation is proposed.
Abstract: OBJECTIVE: Assessing limits of agreement with helium dilution and repeatability of a new system (lung funcution, LUFU) that measures end-expiratory lung volume (EELV) in mechanically ventilated patients using the O(2) washin (EELV(Win)) and washout (EELV(Wout)) technique. LUFU consists of an Evita 4 ventilator, a side-stream oxygen analyzer, and a dedicated PC software. DESIGN AND SETTING: Prospective human study in a general ICU of a University hospital. PATIENTS: Thirty-six mechanically ventilated patients. INTERVENTIONS: We obtained 36 couples of both EELV(Win) and EELV(Wout) measurements in each patient (5 with healthy lungs, 9 with ALI, 22 with ARDS). Measurements were obtained with patients ventilated either by assisted (ASB, 16 measurements) or controlled (CMV, 20 measurements) ventilation. In 19 of 20 cases in CMV, we obtained helium dilution measurements (EELV(He)). MEASUREMENTS AND RESULTS: Bias for agreement with EELV(He) was -16 +/- 156 and 8 +/- 161 ml, respectively, for EELV(Win) and EELV(Wout). Bias for agreement between EELV(Win) and EELV(Wout) was 28 +/- 78 and 23 +/- 168 ml, respectively, for CMV and ASB. During CMV bias for repeatability were 8 +/- 92 and 23 +/- 165 ml, respectively, for EELV(Win) and EELV(Wout). During ASB bias for repeatability were 32 +/- 160 and -15 +/- 147 ml, respectively, for EELV(Win) and EELV(Wout). CONCLUSIONS: The LUFU method showed good agreement with helium, and good repeatability during partial and controlled mechanical ventilation. The technique is simple and safe.
Abstract: OBJECTIVE: Pentraxin 3 is a fluid phase receptor involved in innate immunity. It belongs to the Pentraxins family, as C-reactive protein does. Pentraxin 3 is produced by a variety of tissue cells, whereas only the liver produces C-reactive protein. Pentraxin 3 plays a unique role in the regulation of inflammation. Acute lung injury and acute respiratory distress syndrome are characterized by an important inflammatory reaction. We investigated the role of pentraxin 3 as a marker of severity and outcome predictor of acute lung injury and acute respiratory distress syndrome. DESIGN: We measured circulating pentraxin 3 and C-reactive protein levels within 24 hrs from intubation (day 1), after 24 hrs from the first sample, then every 3 days for the first month and then once a week, until discharge from the intensive care unit. Pentraxin 3 was also measured in bronchoalveolar lavages, performed when clinically indicated. SETTING: One university medical center general intensive care unit. PATIENTS: The study included 21 patients affected by acute lung injury and acute respiratory distress syndrome (1994 Consensus Conference criteria). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pentraxin 3 plasma levels were high with a peak on the first day (median 71.05 ng/mL, interquartile range 52.37-117.38 ng/mL, normal values <2 ng/mL), declining thereafter. C-reactive protein peaked later and remained at relatively high values. Out of several day 1 parameters, pentraxin 3 was the only significant difference between survivors and nonsurvivors. Pentraxin 3 levels were positively correlated with lung injury score values (p < 0.001) and number of organ failures (p < 0.001). Pentraxin 3 was present in bronchoalveolar lavages fluids (5.03 ng/mL, interquartile range 1.52-8.48 ng/mL) and bronchoalveolar lavages positive to bacterial culture were associated with significantly higher pentraxin 3 values (p < 0.05). CONCLUSIONS: The results presented here show that pentraxin 3 is elevated in acute lung injury and acute respiratory distress syndrome and that its levels correlate with parameters of lung injury and systemic involvement. The clinical and pathophysiological significance of pentraxin 3 in acute lung injury and acute respiratory distress syndrome deserves further scrutiny.
Abstract: OBJECTIVE: To assess the behavior of different helmets after discontinuation of fresh gas flow by disconnection at the helmet inlet, flow generator, or gas source. DESIGN AND SETTING: Randomized physiological study in a university research laboratory. PATIENTS: Five healthy volunteers. INTERVENTION: CPAP (FIO2 50%, PEEP 5 cmH2O) delivered in random sequence with three different helmets: 4Vent (Rüsch), PN500 (Harol), CaStar (StarMed) with antisuffocation valve open or locked. For each helmet all three disconnections were randomly employed up to 4 min. MEASUREMENTS AND RESULTS: During flow disconnection we measured: respiratory rate and tidal volume by respitrace; inspiratory and expiratory CO2 concentration, and FIO2 from a nostril; SpO2 by pulse oxymetry. Independently of the site of disconnection we observed a fast increase in CO2 rebreathing and minute ventilation, associated with a decrease in inspired O2 concentration. In the absence of an operational safety valve, larger helmet size and lower resistance of the inlet hose resulted in slower increase in CO2 rebreathing. The presence of the safety valve limited the rebreathing of CO2, and the increase in minute ventilation but did not protect from a decrease in FIO2 and loss of PEEP. CONCLUSIONS: While the use of a safety valve proved effective in limiting CO2 rebreathing, it did not protect from the risk of hypoxia related to decrease in FIO2 and loss of PEEP. In addition to a safety antisuffocation valve, a dedicated monitoring and alarming systems are needed to employ helmet CPAP safely.
Abstract: BACKGROUND: Measuring the work of breathing of patients undergoing spontaneous assisted ventilation can be useful to monitor and titrate ventilatory support. The aim of this study was to obtain measurements of the pressure generated by the respiratory muscles (PMUSC) and the derived pressure-time product (PTP; a good indicator of the metabolic work of breathing), performing the rapid interrupter technique with a commercial ventilator. METHODS: A Draeger Evita 4 ventilator (Draeger Medical, Lubeck, Germany) was controlled by a personal computer to rapidly interrupt the airway flow at different times and volumes of the respiratory cycle during pressure-support ventilation. From the airway pressure tracing after the occlusion, the authors estimated the alveolar pressure and PMUSC; the integration of PMUSC values over the inspiratory time yields the measurement of PTP. Esophageal pressure measurements were used as a reference. After a bench study of the valves' performance, the authors performed 11 measurement sequences in eight patients. RESULTS: The closure times for the inspiratory and expiratory valves were 74 +/- 10 and 61 +/- 13 ms, respectively. The interrupter technique provided a reliable estimate of PMUSC (PMUSC, occl = 1.00 . PMUSC, pes + 0.19; r = 0.88; 95% confidence interval for agreement, +5.49/-5.32 cm H2O). PTPoccl tightly correlated with PTPpes (PTPoccl = 0.95 . PTPpes + 0.13; r = 0.96; 95% confidence interval, 1.94/-1.61 cm H2O . s). CONCLUSION: The rapid interrupter technique can be performed by means of a commercial ventilator, providing reliable measurement of PMUSC and PTP.
Abstract: In critical care medicine there is still a paucity of evidence on how to manage most of the clinical problems commonly encountered in critically ill patients. Randomized controlled trials (RCTs) are the most powerful instruments to evaluate the efficacy of a therapeutic intervention and to generate evidence for clinical practice. Unfortunately, the design and conduct of RCTs in our field are particularly complicated, because of some intrinsic and structural problems (e.g. lack of reliable nosography, concomitant use of different therapies, problems in the definition of end-points besides mortality) that will be discussed in this review. Further challenges are represented by the lack of tradition of large ICU networks, difficulties in linking or integrating physiologic and therapeutic objectives in designing clinical protocols, scarcity of independent or non-profit funds. A particularly stimulating opportunity of development is represented also by the relationship of critical care to EBM. Because of the above problems, metanalyses could be less informative than in other areas of medicine, as they are based on few trials which are often contradictory and of unsatisfactory quality. Few suggestions are formulated which could help looking forwards.
Abstract: BACKGROUND: Regional citrate anticoagulation (RCA) is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients with contraindications to heparin. Its use has been very limited, possibly because of the need for special infusion solutions and difficult monitoring of the metabolic effects. OBJECTIVE: To investigate the safety and the feasibility of an RCA method for continuous veno-venous hemofiltration (CVVH) using commercially available replacement fluid. METHODS: We evaluated 11 patients at high risk of bleeding, requiring CVVH. RCA was performed using commercially available replacement fluid solutions to maintain adequate acid-base balance. We adjusted the rate of citrate infusion to achieve a post-filter ionized calcium concentration [iCa] <0.4 mmol/L when blood flow was <250 ml/min, or <0.6 mmol/L when blood flow was >250 ml/min. When needed, we infused calcium gluconate to maintain systemic plasma [iCa] within the normal range. RESULTS: Twenty-nine filters ran for a total of 965.5 h. Average filter life was 33.6+/-20.5 h. Asymptomatic hypocalcemia was detected in 6.9% of all samples. No [iCa] values <0.9 mmol/L were observed. Hypercalcemia (1.39+/-0.05 mmol/L) occurred in 2.5% of all samples. We observed hypernatremia (threshold 153 mmol/L) and alkalosis (threshold 7.51) in only 9.3% and 9.4% respectively of all samples, mostly concomitantly. No patient showed any signs of citrate toxicity. CONCLUSIONS: We developed a protocol for RCA during CVVH using commercially available replacement fluid that proved safe, flexible and applicable in an Intensive Care Unit (ICU) setting.
Abstract: OBJECTIVE: The importance of echocardiography in the perioperative management of cardiac surgical patients is widely appreciated. A modified mediastinal drain has been developed, which allows the introduction of a standard TEE probe in a closed-ended sleeve coupled with the drain to permit epicardial echocardiographic imaging after chest closure (substernal epicardial echocardiography [SEE]). The aim of the present study was to develop a standardized and comprehensive SEE examination sequence to allow repeatable examinations with a single movement of the TEE probe inside the drain. DESIGN: Prospective observational protocol. SETTING: Tertiary care university hospital. PARTICIPANTS: Ten adult patients undergoing elective cardiac surgery. INTERVENTIONS: Twenty-three SEE examinations in 10 patients undergoing elective myocardial revascularization to develop a standard examination sequence. MEASUREMENTS AND MAIN RESULTS: The examination sequence includes 11 views with all the structures relevant for postoperative monitoring. The entire sequence is performed with a single in-out movement of the transesophageal probe to minimize discomfort to patients and the risk of damaging the tube. CONCLUSIONS: This new approach to the perioperative monitoring of cardiac surgical patients represents an option for patients in whom TEE is contraindicated or multiple examinations are anticipated because SEE examinations can be performed without the need for sedation in awake patients.
Abstract: This study is aimed at assessing the short-term effects of muscular fatigue on the sensorimotor areas organization in the left and right hemispheres. Magnetoencephalographic (MEG) and electromyographic (EMG) activities were simultaneously recorded during the execution of a non-fatiguing motor task, performed before and after a task known to induce muscle fatigue (Fatigue). Coherence between cerebral and muscular rhythms as well as cerebral and muscular rhythms spectral densities were estimated during this non-fatiguing task and at rest. The MEG-EMG coherence in the beta band (13-32 Hz) was higher after than before Fatigue. The background activity reduction during contraction with respect to rest (i.e. the cerebral reactivity) was less evident after than before Fatigue in the gamma (33-45 Hz) and beta bands. When differentiating subjects on the base of Fatigue endurance times, while a huge inter-subject variability was found, an evident intra-subject similarity was observed for left and right arms, suggesting that resistance to fatigue is more an individual ability than a motor skill differentiated for the dominant and non-dominant side. In conclusion, signs of a more selective neural recruitment, more coupled with muscular activity, appeared as short-term effects of muscular fatigue in primary sensorimotor cortical areas. Evidence suggested that the reduction of cortical recruitment and the increased cortico-muscular coupling are distinct mechanisms.
Abstract: BACKGROUND: Limited data are available in our region on out-of-hospital treatment of cardiac arrest. The aim of this study is to evaluate whether the changes implemented in the emergency system (i.e. an increased number of basic life support and advance life support crews that were dispatched) produced the expected outcome improvements. METHODS: (a) Experimental design: data were prospectively collected on patients with sudden out-of-hospital cardiac arrest in three emergency dispatch centers for 3 months during two study periods, year 2000 and year 2003, differentiated only by the increase of qualified crews. Outcomes and survival were evaluated at 24 h and 1 month after the event. (b) Setting: out-of-hospital treatment. (c) Patients: 352 (174 in the second study period) patients suffering cardiac arrest. (d) Interventions: the study was observational. RESULTS: We could document, between the two study periods, stable 24 h (12.6 vs 9.1%) and 1 month survival (3.4 vs 5.8%, NS). Nevertheless, arrival time on site was significantly higher in the second period (from 8.3+/-3.3 to 10.1+/-5.4 min, P<0.05). CONCLUSIONS: The strengthening of only one link of the chain-of-survival did not improve 1 month survival.
Abstract: OBJECTIVES: To measure the performance of selected Italian emergency medical system (EMS) dispatch centres managing calls for patients suffering from stroke. Data on outcome and on early treatment in the ED were collected. METHODS: Prospective data collection for a trimester from interventions for a suspected stroke in 13 EMS dispatch centres over five Italian regions. RESULTS: Altogether, 1041 calls for a suspected stroke were analysed. Mean intervals of the sequential phases were 2.3+/-2 minutes between call and ambulance dispatch, 8.4+/-5.5 minutes to reach the patient, 14.5+/-8.5 minutes on the scene, and 40.2+/-16.2 minutes between call and arrival at the ED. Interventions were performed in 56% of cases by a basic life support (BLS) crew, advanced life support (ALS) crews intervened in 28% of cases, and a combination of ALS and BLS in the remaining 16%. Mean diagnostic interval was 99+/-85 minutes between emergency system call and the first CT scan. This was performed 71+/-27 minutes after ED admission. Only 1.6% were admitted to a stroke unit. One month outcome according to GCS was good recovery in 32%, moderate disability in 28%, severe disability in 14%, and death in 25% of the patients. CONCLUSIONS: Mean times show a rapid response of the selected EMS dispatch centres to calls for a suspected stroke. Nevertheless, mean times of the ED phase are still unacceptable according to international guidelines such as Brain Attack Coalition and American Stroke Association guidelines. Efforts should be spent to reduce the time between the arrival and the CT scan and more patients should be admitted to a stroke unit.
Abstract: BACKGROUND: The "baby lung" concept originated as an offspring of computed tomography examinations which showed in most patients with acute lung injury/acute respiratory distress syndrome that the normally aerated tissue has the dimensions of the lung of a 5- to 6-year-old child (300-500 g aerated tissue). DISCUSSION: The respiratory system compliance is linearly related to the "baby lung" dimensions, suggesting that the acute respiratory distress syndrome lung is not "stiff" but instead small, with nearly normal intrinsic elasticity. Initially we taught that the "baby lung" is a distinct anatomical structure, in the nondependent lung regions. However, the density redistribution in prone position shows that the "baby lung" is a functional and not an anatomical concept. This provides a rational for "gentle lung treatment" and a background to explain concepts such as baro- and volutrauma. CONCLUSIONS: From a physiological perspective the "baby lung" helps to understand ventilator-induced lung injury. In this context, what appears dangerous is not the V(T)/kg ratio but instead the V(T)/"baby lung" ratio. The practical message is straightforward: the smaller the "baby lung," the greater is the potential for unsafe mechanical ventilation.
Abstract: OBJECTIVE: We measured pulmonary edema by thermal indocyanine green-dye double-dilution technique and quantitative computed tomography (CT) in patients with acute respiratory distress syndrome and compared the two techniques. DESIGN AND SETTING: Prospective human study in a university hospital. PATIENTS: Fourteen mechanically ventilated patients with acute respiratory distress syndrome (nine primary; nine with intubation <7 days). INTERVENTIONS: All patients underwent a spiral CT of the thorax. We measured pulmonary thermal volume (PTV) and its components, extravascular lung water and pulmonary blood volume, with an integrated fiberoptic monitoring system (COLD Z-021). MEASUREMENTS AND RESULTS: PTV was tightly correlated with lung weight (LW) measured by CT (PTV = 0.6875 * LW(CT) + 292.77; correlation coefficient = 0.91; p < .0001; bias -11 +/- 8 %). Neither etiology of acute respiratory distress syndrome (primary vs. secondary) nor days of intubation affected the accuracy of thermal dye dilution in comparison with CT. There was no correlation between the extravascular lung water (12.3 +/- 3.4 mL/kg) and CT distribution of lung tissue compartments. Extravascular lung water and pulmonary blood volume showed good reproducibility in 32 pairs of thermal dye dilution measurements. CONCLUSIONS: Measurements of lung edema by thermal indocyanine green-dye double-dilution method show good correlation with those by quantitative computed tomography and good reproducibility in patients with acute respiratory distress syndrome.
Abstract: We report a case in which life support for cardiogenic shock was achieved by a nonpulsatile venoarterial bypass, and left ventricular decompression was obtained by a catheter placed percutaneously through the aortic valve into the left ventricle. The blood drained from the left ventricle was pumped into the femoral artery. The normalization of left heart filling pressures allowed the resolution of pulmonary edema, and the patient underwent a successful heart transplantation following 7 days of mechanical cardiocirculatory support.
Abstract: OBJECTIVE: We describe a simplified helium dilution technique to measure end-expiratory lung volume (EELV) in mechanically ventilated patients. We assessed both its accuracy in comparison with quantitative computerized tomography (CT) and its precision. DESIGN AND SETTING: Prospective human study. PATIENTS: Twenty-one mechanically ventilated ALI/ARDS patients. INTERVENTIONS: All patients underwent a spiral CT scan of the thorax during an end-expiratory occlusion. From the CT scan we computed the gas volume of the lungs (EELVCT). Within a few minutes, a rebreathing bag, containing a known amount of helium, was connected to the endotracheal tube, and the gas mixture diluted in the patient's lungs by delivering at least ten large tidal volumes. From the final helium concentration, EELV could be calculated by a standard formula (EELVHe). MEASUREMENT AND RESULTS: The results obtained by the two techniques showed a good correlation (EELVHe=208+0.858xEELV(CT), r=0.941; P<0.001). Bias between the two techniques was 32.5+/-202.8 ml (95% limits of agreement were -373 ml and +438 ml), with a mean absolute difference of 15%. The amount of pathological tissue did not affect the difference between the two techniques, while the amount of hyperinflated tissue did. Bias between two repeated helium EELV measurements was -24+/-83 ml (95% limits of agreement were -191 ml and +141 ml), with a mean absolute difference of 6.3%. CONCLUSIONS: The proposed helium dilution technique is simple and reproducible. The negligible bias and the acceptable level of agreement support its use as a practical alternative to CT for measuring EELV in mechanically ventilated ARDS patients.
Abstract: Even moderate temperature elevations soon acute cerebral damage may markedly worsen initial brain injury. These effects may justify aggressive antipyretic treatment in neurosurgical intensive care unit (NICU). On the basis of a literature survey, it is observed that fever is extraordinarily common in the neurosurgical intensive care unit during the acute phase of subarachnoid hemorrhage, stroke, and traumatic brain injury. Several clinical studies also suggest worsened neurologic outcome in patients who are febrile compared to those who are not. Pyrexia is more frequent in infected than noninfected patients. Infections (mainly in the respiratory tract) are usually diagnosed in the majority of febrile NICU patients. Laboratory investigations are quite clear regarding the adverse effects of fever in terms not only of functional outcomes, but also histological and neurochemical injury. Even though fever may cause diagnostic confusion (central fever vs infectious), the potentially devastating effects of pyrexia in patients with cerebral diseases may proceed to treat in any case. An attempt to correct fever appears warranted in all patients with acute cerebral damage in order to obtain a better functional recovery and to limit maximally any further insult to the brain. Some of the more common and innovative methods to control body temperature in order to mitigate the detrimental effects of pyrexia following acute neurological injury are explored. Maintenance of normothermia appears to be a desirable therapeutic goal in managing the patients with damaged or at-risk brain tissue. However, it has not been established conclusively that the benefits of antipyretic therapy outweigh its risks and that despite a sound physiologic argument for controlling fever in the brain-injured patient, there is no evidence that doing so will improve their outcome.
Abstract: OBJECTIVE: To assess selected physiological effects of non-invasive continuous positive airway pressure delivered by head helmet (CPAPH), a special interface device designed to completely contain the head of the patient, compared to face mask (CPAPM). DESIGN: Randomized physiological study. SETTING: University research laboratory. PATIENTS: Eight healthy volunteers. INTERVENTION: Continuous positive airway pressure delivered by face mask and CPAPH in random order. Three gas flow rates (20-30-40 l/min and 30-45-60 l/min, respectively, for CPAPM and CPAPH) and four CPAP levels (0-5-10-15 cmH2O) were employed in a randomized sequence. MEASUREMENTS AND RESULTS: In each patient we monitored airway pressure, esophageal pressure, expiratory flow, and inspiratory and expiratory CO2 concentration. End-expiratory lung volume changes from CPAP 0 were measured by inductance plethysmography. The application of increased levels of CPAP resulted in a significant increase in end-expiratory lung volume, similar for CPAPH and CPAPM. Inspiratory changes of airway pressure were comparable for the two CPAP modes. Inspiratory CO2 concentration was higher during CPAPH (significantly decreased at increased gas flow rates), compared to CPAPM. CONCLUSIONS: Continuous positive airway pressure delivered by head helmet is as effective as CPAPM in increasing end-expiratory lung volume and in compensating for airway pressure changes without the need of a reservoir bag. Higher gas flow rates are necessary to maintain a relatively low inspiratory CO2 concentration.
Abstract: OBJECTIVE: To determine whether gas exchange improvement in response to the prone position is associated with an improved outcome in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). DESIGN: Retrospective analysis of patients in the pronation arm of a controlled randomized trial on prone positioning and patients enrolled in a previous pilot study of the prone position. SETTING: Twenty-eight Italian and two Swiss intensive care units. PATIENTS: We studied 225 patients meeting the criteria for ALI or ARDS. INTERVENTIONS: Patients were in prone position for 10 days for 6 hrs/day if they met ALI/ARDS criteria when assessed each morning. Respiratory variables were recorded before and after 6 hrs of pronation with unchanged ventilatory settings. MEASUREMENTS AND MAIN RESULTS: We measured arterial blood gas alterations to the first pronation and the 28-day mortality rate. The independent risk factors for death in the general population were the Pao2/Fio2 ratio (odds ratio, 0.992; confidence interval, 0.986-0.998), the minute ventilation/Paco2 ratio (odds ratio, 1.003; confidence interval, 1.000-1.006), and the concentration of plasma creatinine (odds ratio, 1.385; confidence interval, 1.116-1.720). Pao2 responders (defined as the patients who increased their Pao2/Fio2 by > or =20 mm Hg, 150 patients, mean increase of 100.6 +/- 61.6 mm Hg [13.4 +/- 8.2 kPa]) had an outcome similar to the nonresponders (59 patients, mean decrease -6.3 +/- 23.7 mm Hg [-0.8 +/- 3.2 kPa]; mortality rate 44% and 46%, respectively; relative risk, 1.04; confidence interval, 0.74-1.45, p =.65). The Paco2 responders (defined as patients whose Paco2 decreased by > or =1 mm Hg, 94 patients, mean decrease -6.0 +/- 6 mm Hg [-0.8 +/- 0.8 kPa]) had an improved survival when compared with nonresponders (115 patients, mean increase 6 +/- 6 mm Hg [0.8 +/- 0.8 kPa]; mortality rate 35.1% and 52.2%, respectively; relative risk, 1.48; confidence interval, 1.07-2.05, p =.01). CONCLUSION: ALI/ARDS patients who respond to prone positioning with reduction of their Paco2 show an increased survival at 28 days. Improved efficiency of alveolar ventilation (decreased physiologic deadspace ratio) is an important marker of patients who will survive acute respiratory failure.
Abstract: The evolution of the nurse role in out of hospital life support yielded to the employment of tools typical of in-hospital setting, like helmet delivered CPAP. Some elements in the use of this tool have been analyzed: indications, contraindications, application modality and protocol, patient's record, practical aspects of the treatment and problems related to the material employed. Data concerning the application of this technique in 21 patients confirm the indication for its use in advanced nurse out of hospital life support.
Abstract: BACKGROUND: Based on available data, there is no definite clinical research describing option, timing and effects of assisted as opposed to controlled ventilation to successfully treat acute severely brain-injured patients. This study demonstrates pressure support ventilation as a possible alternative to controlled ventilation in the acute phase of brain injury. We illustrated which factors influenced the shift from total (CPPV) to partial ventilatory support (PS-SIGH) and the consequences of assisted ventilation on cerebral hemodynamics. METHODS: a) Experimental design: Retrospective, cohort study. b) Setting: Adult intensive care unit of a university hospital. c) Patients population: Forty-two severe head-trauma victims (GCS </= 8). d) Measures and interventions: Ventilation modalities and parameters, systemic and cerebral hemodynamics [Intracranial pressure (ICP), cerebral perfusion pressure (CPP), jugular bulb oxygen saturation (SjvO(2))] data were collected daily and described. RESULTS: Controlled ventilation was the main ventilatory support during the very first moment of brain trauma. Percentage of patients ventilated with pressure support increased progressively (37.5% on day 2) and was the dominant method of ventilation on the fourth day. Worst neurologic condition and more elevated ICP were associated to controlled ventilation. Carbon dioxide partial pressure was higher in PS-SIGH, however, it was not correlated with significantly elevated ICP. CONCLUSIONS: In traumatic brain injured patients, ICP and CPP monitoring, together with neurological examination are the main factors influencing the selection of ventilatory assistance. It is evident from these data that assisted ventilation is a feasible and safe alternative to controlled ventilation even in the acute phase of trauma if intracranial parameters are continuously monitored and controlled.
Abstract: BACKGROUND: The aim of our study was to assess the effect of periodic hyperinflations (sighs) during pressure support ventilation (PSV) on lung volume, gas exchange, and respiratory pattern in patients with early acute respiratory distress syndrome (ARDS). METHODS: Thirteen patients undergoing PSV were enrolled. The study comprised 3 steps: baseline 1, sigh, and baseline 2, of 1 h each. During baseline 1 and baseline 2, patients underwent PSV. Sighs were administered once per minute by adding to baseline PSV a 3- to 5-s continuous positive airway pressure (CPAP) period, set at a level 20% higher than the peak airway pressure of the PSV breaths or at least 35 cm H2O. Mean airway pressure was kept constant by reducing the positive end-expiratory pressure (PEEP) during the sigh period as required. At the end of each study period, arterial blood gas tensions, air flow and pressures traces, end-expiratory lung volume (EELV), compliance of respiratory system (Crs), and ventilatory parameters were recorded. RESULTS: Pao2 improved (P < 0.001) from baseline 1 (91.4 +/- 27.4 mmHg) to sigh (133 +/- 42.5 mmHg), without changes of Paco2. EELV increased (P < 0.01) from baseline 1 (1,242 +/- 507 ml) to sigh (1,377 +/- 484 ml). Crs improved (P < 0.01) from baseline 1 (40.2 +/- 12.5 ml/cm H2O) to sigh (45.1 +/- 15.3 ml/cm H2O). Tidal volume of pressure-supported breaths and the airway occlusion pressure (P0.1) decreased (P < 0.01) during the sigh period. There were no significant differences between baselines 1 and 2 for all parameters. CONCLUSIONS: The addition of 1 sigh per minute during PSV in patients with early ARDS improved gas exchange and lung volume and decreased the respiratory drive.
Abstract: OBJECTIVE: To prevent gas exchange deterioration during translaryngeal tracheostomy (TLT) in patients with acute respiratory distress syndrome (ARDS) ventilation is maintained through a small diameter endotracheal tube (ETT; 4.0 mm i.d.) advanced beyond the tracheostoma. We report on the feasibility of uninterrupted ventilation delivered through a high-resistance ETT in ARDS patients, and relevant ventilatory adjustments and monitoring. DESIGN AND SETTING: Prospective, observational clinical study in an eight-bed intensive care unit of a university hospital. Patients: Eight consecutive ARDS patients scheduled for tracheostomy. INTERVENTIONS: During TLT volume control ventilation was maintained through the 4.0-mm i.d. ETT. Tidal volume, respiratory rate, and inspiratory to expiratory ratio were kept constant. Fractional inspiratory oxygen was 1. Positive end expiratory pressure (PEEP) set on the ventilator (PEEP(vent)) was reduced to maintain total PEEP (PEEP(tot)) at baseline level according to the measured intrinsic PEEP (auto-PEEP). MEASUREMENTS AND MAIN RESULTS: Data were collected before tracheostomy and while on mechanical ventilation with the 4.0-mm i.d. ETT. Neither PaCO(2) nor PaO(2) changed significantly (54.5+/-10.0 vs. 56.4+/-7.0 and 137+/-69 vs. 140+/-59 mmHg, respectively). Auto-PEEP increased from 0.6+/-1.1 to 9.8+/-6.5 cmH(2)O during ventilation with the 4.0-mm i.d. ETT. By decreasing PEEP(vent) we obtained a stable PEEP(tot) (11.4+/-4.3 vs. 11.8+/-4.3 cmH(2)O), and end-inspiratory occlusion pressure (26.7+/-7.4 vs. 28.0+/-6.6 cmH(2)O). Peak inspiratory pressure rose from 33.8+/-8.1 to 77.8+/-12.7 cmH(2)O. CONCLUSIONS: The high-resistance ETT allows ventilatory assistance during the whole TLT procedure. Assessment of stability in plateau pressure and PEEP(tot) by end-inspiratory and end-expiratory occlusions prevent hyperinflation and possibly barotrauma.
Abstract: A novel multiple, sequential image fusion (MuSIF) procedure merging stereotaxic CT with frameless magnetic resonance imaging (MRI) is used since June 2000 to visualise and directly localise the subthalamic nucleus (STN) on T2 images. In 13 consecutive Parkinson's cases, intraoperative recording and stimulation verified bilateral electrode implantation guided by fused T2 images. In 85% of sides, final implantation opted for visualised target track. Implanted electrode position on postoperative T2 images matched planned target. Clinical follow-up reproduces literature's best results. This MuSIF technique, effective for direct STN targeting, has practical advantages: MRI can be performed regardless of surgery time; regular MR scanning to correct real image distortion is unneeded; and the need for multiple localising tracks is reduced by enabling us to account for each patient's STN anatomy.
Abstract: BACKGROUND: The aim of this research is to evaluate quality of out-of-hospital medical services in our country, using performance indicators and a new computerised database. METHODS: (a) EXPERIMENTAL DESIGN: Data were collected prospectively in three emergency dispatch centres for 90 days. Follow-up was evaluated at 1 day and 1 month after the event. This paper presents data on the cardiac arrest cohort only. (b) SETTING: Three emergency dispatch centres in Lombardia. (c) PATIENTS: One hundred and seventy-eight patients in non-traumatic cardiac arrest were enrolled. (d) INTERVENTIONS: None. The study was observational only. RESULTS: Mean interval between phone call and arrival on scene was 8.5+/-3.5 min. BLS manoeuvres were carried out from bystanders only in 15% of the cohort; this was associated with significant mortality reduction (85.7 versus 95.8%, chi(2) P<0.05). One hundred and thirty-three patients (75%) received assistance from BLS crews while only 45 patients (25%) were assisted by ALS medical personel, with a significant mortality reduction (ALS deaths 86.7%, BLS deaths 97%). Total 24 h survival was 9% and survival at 1 month declined to 6.17%. CONCLUSIONS: Quality monitoring produces objective information on interventions and outcomes. Only with this information, is it possible to implement improvement programmes that are planned according to the data presented.
Abstract: OBJECTIVE: A closed suction system (CS) maintains connection with the mechanical ventilator during tracheal suctioning and is claimed to limit loss in lung volume and oxygenation. We compared changes in lung volume, oxygenation, airway pressure and hemodynamics during endotracheal suctioning performed with CS and with an open suction system (OS). DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: We enrolled ten patients, volume-controlled (VC) ventilated with a Siemens Servo 900 ventilator (PaO2/FIO2 192 +/- 70, PEEP 10.7 +/- 3.9 cmH2O). INTERVENTIONS: We performed four consecutive tracheal suction maneuvers, two with CS and two with OS, at 20-min intervals. During the suction maneuvers continuous suction was applied for 20 s. MEASUREMENTS AND MAIN RESULTS: We measured end-expiratory lung volume changes (delta VL), tidal volume (VTrt), respiratory rate (RR) and minute volume (VErt) by respiratory inductive plethysmography; arterial oxygen saturation (SpO2), airway pressure and arterial pressure (PA). Loss in lung volume during OS (delta VL 1.2 +/- 0.7 l) was significantly higher than during CS (delta VL 0.14 +/- 0.1 l). During OS we observed a marked drop in SpO2, while during CS the change was only minor. During CS ventilation was not interrupted and we observed an immediate increase in RR (due to the activation of the ventilator's trigger), while VTrt decreased, VErt was maintained. CONCLUSIONS: Avoiding suction-related lung volume loss can be helpful in patients with an increased tendency to alveolar collapse; CS allows suctioning while avoiding dramatic drops in lung volumes and seems to be safe during the VC ventilation setting that we used.
Abstract: OBJECTIVE: To evaluate the effect of a stepwise increase in intra-abdominal pressure (IAP) on intracranial pressure (ICP) and to further define the pressure transmission characteristics of different body compartments. DESIGN: A prospective, nonrandomized study. SETTING: A multidisciplinary intensive care unit at a university medical center. PATIENTS: Fifteen patients with moderate-to-severe head injury. INTERVENTIONS: All patients were studied after the initial stabilization and resolution of intracranial hypertension. Measurements were carried out before and 20 mins after IAP was increased by positioning a soft, 15-L water bag on the patient's abdomen. MEASUREMENTS AND MAIN RESULTS: Placing weights upon the abdomen generated a significant increase in IAP, which rose from 4.7 +/- 2.9 to 15.5 +/- 4.1 mm Hg (p <.001). The rise in IAP caused concomitant and rapid increases in central venous pressure (from 6.2 +/- 2.4 to 10.4 +/- 2.9 mm Hg; p <.001), internal jugular pressure (from 11.9 +/- 3.2 to 14.3 +/- 2.4 mm Hg; p <.001), and ICP (from 12.0 +/- 4.2 to 15.5 +/- 4.4 mm Hg; p <.001). Thoracic transmural pressure, calculated as the difference between central venous pressure and esophageal pressure, remained constant during the protocol. Respiratory system compliance decreased from 58.9 +/- 9.8 to 44.9 +/- 9.4 mL/cm H2O (p <.001) in all patients because of decreased chest wall compliance. The mean arterial pressure increased from 94 +/- 11 to 100 +/- 13 mm Hg (p <.01), which allowed the maintenance of a stable cerebral perfusion pressure (82.4 +/- 10.3 vs. 84.7 +/- 11.5 mm Hg; p = NS) despite the ICP increase. CONCLUSIONS: Increased IAP causes a significant rise in ICP in head trauma patients. This effect seems to be the result of an increase in intrathoracic pressure, which causes a functional obstruction to cerebral venous outflow. Routine assessment of IAP may help clinicians to identify remediable causes of increased ICP. Caution should be used when applying laparoscopic techniques in neurotrauma patients.
Abstract: Computerised tomography (CT) is being used with increasing frequency in acute respiratory distress syndrome (ARDS) patients. This brief review will discuss some of the clinical insights that a CT scan can offer. A large number of CT scan studies have provided new insights into the pathophysiology of ARDS and of mechanical ventilation, and are particularly focused on the recruitment-derecruitment phenomenon. To this end, newer fast CT scan technology promises a dynamic, rather than a static view of lung ventilation.
Abstract: BACKGROUND: Although placing patients with acute respiratory failure in a prone (face down) position improves their oxygenation 60 to 70 percent of the time, the effect on survival is not known. METHODS: In a multicenter, randomized trial, we compared conventional treatment (in the supine position) of patients with acute lung injury or the acute respiratory distress syndrome with a predefined strategy of placing patients in a prone position for six or more hours daily for 10 days. We enrolled 304 patients, 152 in each group. RESULTS: The mortality rate was 23.0 percent during the 10-day study period, 49.3 percent at the time of discharge from the intensive care unit, and 60.5 percent at 6 months. The relative risk of death in the prone group as compared with the supine group was 0.84 at the end of the study period (95 percent confidence interval, 0.56 to 1.27), 1.05 at the time of discharge from the intensive care unit (95 percent confidence interval, 0.84 to 1.32), and 1.06 at six months (95 percent confidence interval, 0.88 to 1.28). During the study period the mean (+/-SD) increase in the ratio of the partial pressure of arterial oxygen to the fraction of inspired oxygen, measured each morning while patients were supine, was greater in the prone than the supine group (63.0+/-66.8 vs. 44.6+/-68.2, P=0.02). The incidence of complications related to positioning (such as pressure sores and accidental extubation) was similar in the two groups. CONCLUSIONS: Although placing patients with acute respiratory failure in a prone position improves their oxygenation, it does not improve survival.
Abstract: OBJECTIVE: We wished to investigate whether volume recruitment maneuvers (VRMs) could improve alveolar recruitment and oxygenation in acute respiratory distress syndrome (ARDS) patients, ventilated at relatively low positive end-expiratory pressure (PEEP). SETTING: General intensive care unit (ICU) located in a teaching hospital. PATIENTS: 15 PEEP responder ARDS patients undergoing continuous positive pressure ventilation (CPPV) with sedation and muscle paralysis. INTERVENTIONS: We identified a low (9.4 +/- 3 cmH2O) and a high (16.0 +/- 2 cmH2O) level of PEEP associated with target oxygenation values. Using a custom modified mechanical ventilator, we applied in random order three steps lasting 30 min: (1) CPPV at the low PEEP level (CPPV(LO)); (2) CPPV at the high PEEP level (CPPV(HI)); (3) CPPV at low PEEP with the superimposition of periodic VRMs (CPPV(VRM)). VRMs were performed twice a minute by increasing PEEP to the high level for two breaths. Each brace of two breaths was spaced 30 seconds from the preceding one. MEASUREMENTS AND RESULTS: We measured gas exchange, hemodynamics, respiratory mechanics, and the end expiratory lung volume (EELV). Compared to CPPV(LO), CPPV(VRM) resulted in higher PaO2 (117.9 +/- 40.6 vs 79.4 +/- 13.6 mmHg, P < 0.01) and EELV (1.50 +/- 0.62 vs 1.26 +/- 0.50 l, P < 0.05), and in lower venous admixture (Q(VA)/Q(T)) (0.42 +/- 0.07 vs 0.48 +/- 0.07, P < 0.01). During CPPV(HI), we observed significantly higher PaO2 (139.3 +/- 32.5 mmHg) and lower Q(VA)/Q(T) (0.37 +/- 0.08) compared to CPPV(LO) (P < 0.01) and to CPPV(VRM) (P < 0.05). CONCLUSIONS: VRMs can improve oxygenation and alveolar recruitment during CPPV at relatively low PEEP, but are relatively less effective than a continuous high PEEP level.
Abstract: OBJECTIVES: To assess the success rate of pressure support ventilation (PSV) in acute lung injury patients undergoing continuous positive pressure ventilation (CPPV), to study physiologic changes after the transition from CPPV to PSV, and to investigate differences between patients who succeed and patients who fail PSV according to predetermined criteria. DESIGN: Observational study. SETTING: General intensive care unit in a teaching hospital. SUBJECTS: We studied 48 patients having acute lung injury, as defined by a PaO2/F(IO2) <300 mm Hg and the presence of bilateral infiltrates on chest radiograph, and ventilated with CPPV. We included patients with PaO2 >80 mm Hg, at positive end-expiratory pressure of <15 cm H2O and with F(IO2) up to 1.0. INTERVENTIONS: After enrollment, PSV was instituted and patients were strictly monitored during the following 48 hrs. Subjects who met any of the predefined PSV failure criteria during this period were returned to CPPV (Group F). PSV was continued in the remaining patients (Group S). MEASUREMENTS AND MAIN RESULTS: Gas exchange, respiratory mechanics, and hemodynamics measurements were collected before switching from CPPV to PSV and were repeated at 24 hrs after beginning PSV, or immediately before return to CPPV in Group F patients. The physiologic deadspace volume to tidal volume ratio (V(D)/V(T)) was obtained by the Enghoff's equation from the measurement of the mixed expired CO2 fraction. PSV resulted in a significant PaCO2 decrease (49.2+/-10.9 mm Hg to 44.4+/-7.2 mm Hg) and significant increases in minute volume (V(E))(9.0+/-2.3 L/min to 12.0+/-4.0 L/min) and arterial blood pH (7.405+/-0.054 to 7.435+/-0.064), with stable oxygenation and hemodynamics. In patients who were hypercapnic (PaCO2 >50 mm Hg) during CPPV, the V(E) increase was higher than in normocapnic patients. In the latter patients, PaCO2 and pH did not change significantly going from CPPV to PSV. A total of 38 patients (79%) were allocated to Group S and the remaining 10 patients were included in Group F. In Group S, positive endexpiratory pressure of 9.4+/-2.9 cm H2O (range, 3-14 cm H2O) and a PSV level of 14.9+/-3.8 cm H2O (range, 9-22 cm H2O) were applied. In Group F, positive end-expiratory pressure of 8.9+/-3.1 cm H2O (range, 5-15 cm H2O) and a PSV level of 21.6+/-4.6 cm H2O (range, 16-31 cm H2O) were adopted. Compared with Group S, Group F had a longer duration of intubation (20.2+/-19.2 days vs. 9.2+/-13.5 days), a lower static compliance of the respiratory system (30.4+/-16.5 mL/cm H2O vs. 41.7+/-15.0 mL/cm H2O), and a higher V(D)/V(T) (0.70+/-0.09 vs. 0.52+/-0.10), but similar oxygenation and positive end-expiratory pressure. V(E) was higher in Group F during both CPPV and PSV. CONCLUSIONS: In a relatively high proportion of the investigated patients, PSV was successful. The institution of PSV led to no major changes in oxygenation or in hemodynamics. PSV was associated with increases in V(E) and respiratory frequency. In patients who had been hypercapnic during CPPV, PaCO2 decreased despite a compensated pH. Compared with PSV success patients, patients who failed PSV appeared to be sicker, as shown by the higher duration of respiratory support, increased ventilatory needs, and decreased respiratory system compliance, despite similar arterial oxygenation and positive end-expiratory pressure.
Abstract: OBJECTIVES: The aim of this study was to assess the efficacy and safety of low doses of diclofenac sodium (DCF) in attaining normothermia with minimal major side effects in patients with acute cerebral damage. The study was designed to verify the adequate, prolonged antipyretic action of DCF infusion, to quantify its haemodynamic and cerebral impact and to assess any negative effect on renal and liver function. DESIGN: Retrospective, cohort study on prospectively collected data. SETTING: Intensive care unit (ICU) of a university hospital. PATIENT POPULATION: Five patients with subarachnoid haemorrhage and seven severe head-trauma victims with febrile illness of various infectious origin. INTERVENTIONS: Continuous i.v. infusion of a low dose (0.04 mg/kg/h) of DCF for 48 h. MEASUREMENTS AND RESULTS: Systemic and cerebral haemodynamic data were collected at 4 h intervals for 8 h before diclofenac infusion and 48 h after. Renal and liver functions were monitored. Normothermia, defined as external temperature < 37.5 degrees Celsius (degrees C), was achieved in all cases. Intracranial pressure was significantly lowered and mean arterial pressure was unaffected, so cerebral perfusion pressure rose after DCF. Hepatic and renal function were not altered in the 48 h post DCF. Mean urinary output was preserved at high flow and was not influenced by DCF. CONCLUSIONS: Continuous infusion of low-dose DCF attained normothermia without any major cerebral or systemic side effects. Renal and liver functions were unaffected. Once normothermia was achieved, intracranial and cerebral perfusion pressure improved.
Abstract: Techniques of tracheal gas insufflation (TGI) have been shown to enhance CO(2) clearance efficiency in mechanically ventilated patients with acute respiratory distress syndrome (ARDS). Clinical studies have explored the effects of such techniques only at moderate intratracheal gas flow rates, with TGI superimposed to mechanical ventilation in a continuous fashion, or synchronized to the expiratory phase of the duty cycle. We examined the effects of intratracheal pulmonary ventilation (ITPV), delivering the entire tidal volume (VT) in the proximity of the tracheal carina, with all the gas flow supplied continuously through a reverse-thrust catheter (RTC). A potential limitation in the application of TGI is dynamic hyperinflation. Therefore, in a subgroup of patients, we also evaluated the effects of ITPV on end-expiratory lung volume (EELV) by respiratory inductive plethysmography (RIP). Eleven patients with ARDS under volume-cycled mechanical ventilation were subsequently switched to ITPV at the same baseline respiratory rate, I:E ratio, and VT. At the same minute volume, Pa(CO(2)) decreased from 70 +/- 12.3 to 59 +/- 9.5 mm Hg, with a percent reduction of 15 +/- 4% (range from 10 to 20%). The CO(2) decrease was greater in patients with higher baseline Pa(CO(2)) levels (DeltaPa(CO(2)) = 0.29 x Pa(CO(2)) - 9.48, r = 0.95). During transition from mechanical ventilation to ITPV, tracheal positive end-expiratory pressure (PEEP(tr)) decreased with a correspondent decrease in EELV. Both were restored by increasing the PEEP at the ventilator by 3.6 +/- 2.0 cm H(2)O. These data suggest that in patients with ARDS ITPV effectively reduces dead space ventilation and the employment of the RTC may limit or avoid dynamic hyperinflation.
Abstract: OBJECTIVE: To analyze the single effect and the interaction of prone position and inhaled nitric oxide (iNO) on lung function and hemodynamic variables. DESIGN: 2 x 2 factorial trial. SETTING: Department of intensive care medicine at a university hospital. PATIENTS: Fourteen patients on volume-controlled mechanical ventilation for acute respiratory distress syndrome (ARDS). INTERVENTION: Four experimental conditions, each one characterized by the patient's position (supine or prone) with iNO or without iNO. MEASUREMENTS AND RESULTS: Hemodynamic and gas exchange data were collected for each experimental condition. PaO2 was increased both by positioning (p < .01) and iNO (p < .01); iNO caused also a reduction in venous admixture (p < .01), pulmonary artery pressure (p < .01), and pulmonary vascular resistance index (p < .05). We could not demonstrate any significant interaction between the two treatments. The average effect of prone positioning was the same both with and without iNO, whereas the average effect of iNO was the same in both the prone and the supine position. CONCLUSION: In the studied acute respiratory distress syndrome patients the average effects of iNO and positioning on oxygenation were additive and no interaction could be shown. A strategy including both treatments could warrant the best improvement in oxygenation, and should take into account the individual response to each treatment and the possible combination of the two.
Abstract: PURPOSE: To assess the differences in CT appearance between adult respiratory distress syndrome due to pulmonary disease (ARDSP) and that due to extrapulmonary disease (ARDSEXP) and determine whether the variable appearances of ARDS are due, in part, to the initial pulmonary and systemic causes. MATERIALS AND METHODS: Thirty-three patients, 22 with ARDSP and 11 with ARDSEXP, underwent helical CT shortly after intubation. Two readers evaluated images for the type, extent, and distribution of pulmonary opacities; secondary findings; and correlation with survival and physiologic parameters. RESULTS: In both ARDSP and ARDSEXP, approximately 80% of the lung was abnormal. In ARDSP, ground-glass opacification and consolidation were equally prevalent, whereas in ARDSEXP ground-glass opacification was dominant. Ground-glass opacification was evenly distributed, whereas consolidation tended to be dorsal and caudal. ARDSP often caused asymmetric consolidation, whereas ARDSEXP caused symmetric ground-glass opacification. Air bronchograms were almost universal. Pleural effusions were present in one-half of the patients, and Kerley B lines and pneumatoceles were uncommon. Lung consolidation correlated with the ratio of mean partial pressure of arterial oxygen to fraction of inspired oxygen, shunt fraction, and pulmonary arterial pressure. The patients who died tended to have more consolidation and asymmetric disease. CONCLUSION: ARDSP tends to be asymmetric, with a mix of consolidation and ground-glass opacification, whereas ARDSEXP has predominantly symmetric ground-glass opacification. In both groups, pleural effusions and air bronchograms are common, and Kerley B lines and pneumatoceles are uncommon.
Abstract: OBJECTIVE: To compare the effects of continuous negative extrathoracic pressure (CNEP) and positive end-expiratory pressure (PEEP) at the same level of transpulmonary pressure. DESIGN: Prospective analysis. SETTING: Medical intensive care unit of a university hospital. PATIENTS: Nine consecutive acute lung injury patients. Patients with cardiac failure and patients with chronic lung disease were excluded from the investigation. INTERVENTIONS: The patients were sedated and paralyzed while receiving mechanical ventilation and were studied in three different conditions: a) using a PEEP of 0 cm H2O (zero end-expiratory pressure); b) using a PEEP of 15 cm H2O; c) using CNEP. CNEP was applied to the thorax and the upper abdomen and its level was chosen to obtain a transpulmonary pressure similar to the one observed at a PEEP of 15 cm H2O. All patients had an arterial catheter, a pulmonary artery catheter, and a thermistor-tip fiberoptic catheter for thermo-dye-dilution in the femoral artery. These catheters were connected to an integrated monitoring system. We also placed an esophageal catheter in each patient to detect esophageal pressure. MEASUREMENTS AND MAIN RESULTS: For each step, we assessed the hemodynamic variations by measuring intravascular pressures (via a pulmonary artery catheter), transmural pressures (computed by subtracting esophageal pressure from intravascular pressure), and blood volumes (derived from the technique of double indicator). The application of CNEP of -20+/-0.7 cm H2O produced a venous admixture and PaO2/FO2 improvement similar to that obtained with a PEEP of 15 cm H2O. This procedure is associated with a higher cardiac index (5.5+/-1.5 vs. 4.6+/-1.2 L/min/m2; p < .05) coupled with lower central venous pressure, pulmonary artery occlusion pressure, and higher transmural pressures and blood volume parameters. CONCLUSIONS: In acute lung injury patients, a CNEP of -20 cm H2O has the capability to obtain transpulmonary pressure and lung function improvement similar to a PEEP of 15 cm H2O. CNEP differs from the positive pressure by increasing the venous return and the preload of the heart, and has no negative effects on cardiac performance.
Abstract: We evaluated the end-inspiratory occlusion maneuver as a means to estimate the inspiratory effort during pressure support ventilation (PS). In nine nonobstructed acute lung injury (ALI) patients, we applied four levels of PS (0, 5, 10, 15 cm H2O) to modify the inspiratory effort. End inspiratory occlusions (2 to 3 s) were performed at the end of each experimental period by pushing the inspiratory hold button of the ventilator (Servo 900 C; Siemens, Berlin, Germany). We took the difference between the end-inspiratory occlusion plateau pressure and the airway pressure before the occlusion (PEEP + PS) as an estimate of the inspiratory effort and called it PMI (Pmusc,index). From the esophageal pressure tracing we obtained a reference measurement of the pressure developed by the inspiratory muscles at end inspiration (Pmusc,ei) and of the pressure-time product per breath (PTP/b) and per minute (PTP/min). In each patient, PMI was correlated with Pmusc,ei (p < 0.01) and PTP/b (p < 0.01). A PMI threshold of 6 cm H2O detected PTP/min < 125 cm H2O s/min with a sensitivity of 0.89 and a specificity of 0.89. We conclude that PMI is a good estimate of the pressure developed by the inspiratory muscles in ALI patients and may be used to titrate PS level. The major advantage of PMI is that it can be obtained from the ventilator display without any additional equipment.
Abstract: Truncus arteriosus Type IV is a rare congenital cardiac malformation characterized by agenesis of the pulmonary arteries. Pulmonary perfusion is ensured by bronchial arteries. One common arterial trunk arises from both ventricles and systemic pulmonary and coronary arteries originate from this common vessel. Survival is rare without surgical correction. We report a case of uncorrected truncus arteriosus Type IV in a 28-year-old primigravid woman who underwent caesarean section.
Abstract: In order to assess the relative contribution of the lung and the chest wall to the derangements of respiratory mechanics in chronic obstructive pulmonary disease (COPD) patients with acute ventilatory failure (AVF), we studied eight COPD patients undergoing controlled mechanical ventilation for AVF and nine normal subjects anaesthetized for surgery as a control group. With the use of the interrupter technique together with the oesophageal balloon technique we measured: static lung and chest wall elastances (E[st,L] and E[st,w], respectively), maximum (R[L,max]), minimum (R[L,min]) and additional (deltaR[L]) lung resistances, additional chest wall resistance (deltaRw) and, in the COPD group, total intrinsic positive end-expiratory pressure (PEEPtot). Measurements were repeated at 0, 5, 10 and 15 cmH2O of applied positive end-expiratory pressure (PEEP). We found that, in the COPD group: 1) both E(st,w) and deltaRw were higher than in the normal group; 2) R(L,max) was markedly increased due to an increase of both R(L,min) and deltaRL; 3) even low levels of PEEP increased PEEPtot; 4) PEEP did not reduce elastance or total resistance of either the lung or the chest wall. We conclude that chest wall mechanics are abnormal in chronic obstructive pulmonary disease patients with acute ventilatory failure undergoing controlled mechanical ventilation and that positive end-expiratory pressure does not seem to be effective in reducing either elastance or resistance of the lung or chest wall.
Abstract: STUDY OBJECTIVE: To study the effect of positive end-expiratory pressure (PEEP) on the decay of respiratory system compliance (Cpl,rs) due to low tidal volume (VT) ventilation in acute lung injury (ALI) patients. SETTING: General ICU in a university hospital. PARTICIPANTS: Eight ALI patients with a lung injury score greater than 2.5. INTERVENTION: Pressure-controlled ventilation (PCV) and volume-controlled ventilation (VCV), with an average VT of 8.5 +/- 0.4 mL/kg, were applied at three levels of PEEP (5, 10, and 15 cm H2O). Before each PCV and VCV period, lung volume history was standardized by manual hyperinflation maneuvers. MEASUREMENTS: We measured Cpl,rs at time 0 (start), 10, 20, and 30 (end) min from the beginning of each PCV and VCV period. Gas exchange and hemodynamic data were collected at end. RESULTS: At PEEP 5 and 10 cm H2O, we observed a progressive Cpl,rs decay with both PCV and VCV modes. At PEEP 5 cm H2O, we detected a higher Cpl,rs decrease during PCV, due to a higher Cpl,rs at start, compared with VCV. At PEEP 15 cm H2O, Cpl,rs did not decrease significantly. Cpl,rs values measured at end as well as oxygenation and hemodynamic data did not differ between PCV and VCV. At PEEP 15 cm H2O, PCV provided lower PaCO2 than VCV. CONCLUSIONS: A PEEP of at least 15 cm H2O was needed to prevent Cpl,rs decay. The progressive Cpl,rs loss we observed at lower PEEP probably reflects alveolar instability.
Abstract: Plasma leakage has been regarded as the main technical problem during prolonged extracorporeal circulation (ECC) with microporous membrane oxygenators (MMOs). We report the case of a 15 year old male who underwent long term ECC for ARDS and in whom, by using new MMOs with reduced pore size, we were able to achieve prolonged artificial gas exchange efficiency with minimal plasma leakage. We conclude that reduced pore size MMOs might represent a valuable technical advance in extracorporeal oxygenation therapy.
Abstract: OBJECTIVE: We have investigated the role that improvement in arterial oxygenation has, consequent on positive end-expiratory pressure (PEEP), in the reduction of cardiac index (CI) determined by applying PEEP. DESIGN: 2 x 2 factorial trial. SETTING: Department of intensive care medicine at a university hospital. PATIENTS: 13 patients on mechanical ventilation for acute lung injury. INTERVENTIONS: Four experimental conditions, each one characterized by one level of PEEP and one level of PaO2: LOLP = Low PaO2 (approximately 50 mmHg) Low PEEP (approximately 1 cmH2O) LOHP = Low PaO2 (approximately 50 mm Hg) High PEEP (approximately 10 cmH2O) HOLP = High PaO2 (approximately 80 mmHg) Low PEEP (approximately 1 cmH2O) HOHP = High PaO2 (approximately 80 mmHg) High PEEP (approximately 10 cmH2O) MEASUREMENTS AND RESULTS: Hemodynamic and gas exchange data were collected for each experimental condition. CI showed a 13% decline from LOLP (7.0 +/- 1.71/min per m2) to HOHP (6.1 +/- 1.31/min per m2). Both the direct effect of PEEP on the CI (LOLP + HOLP vs LOHP + HOHP, p < 0.01) and the indirect effect related to the improvement in oxygenation (LOLP + LOHP vs HOLP + HOHP, p < 0.01) contributed to the reduction in CI. CONCLUSIONS: In evaluating CI changes induced by PEEP we should take into account the indirect effect of arterial oxygenation upon CI. This should be considered, at least in part, as a physiological adjustment rather than as impaired cardiovascular performance.
Abstract: BACKGROUND. Hemodynamic therapy to raise the cardiac index and oxygen delivery to supranormal may improve outcomes in critically ill patients. We studied whether increasing the cardiac index to a supranormal level (cardiac-index group) or increasing mixed venous oxygen saturation to a normal level (oxygen-saturation group) would decrease morbidity and mortality among critically ill patients, as compared with a control group in which the target was a normal cardiac index. METHODS. A total of 10,726 patients in 56 intensive care units were screened, among whom 762 patients belonging to predefined diagnostic categories with acute physiology scores of 11 or higher were randomly assigned to the three groups (252 to the control group, 253 to the cardiac-index group, and 257 to the oxygen-saturation group). RESULTS. The hemodynamic targets were reached by 94.3 percent of the control group, 44.9 percent of the cardiac-index group, and 66.7 percent of the oxygen-saturation group (P < 0.001). Mortality was 48.4, 48.6, and 52.1 percent, respectively (P = 0.638), up to the time of discharge from the intensive care unit and 62.3, 61.7, and 63.8 percent (P = 0.875) at six months. Among patients who survived, the number of dysfunctional organs and the length of the stay in the intensive care unit were similar in the three groups. No differences in mortality among the three groups were found for any diagnostic category. A subgroup analysis of the patients in whom hemodynamic targets were reached revealed similar mortality rates: 44.8, 40.4, and 39.0 percent, respectively (P = 0.478). CONCLUSIONS. Hemodynamic therapy aimed at achieving supranormal values for the cardiac index or normal values for mixed venous oxygen saturation does not reduce morbidity or mortality among critically ill patients.
Abstract: In 16 mechanically ventilated patients with acute lung injury (ALI) (eight patients with moderate ALI [moderate group], eight patients with severe ALI [adult respiratory distress syndrome, ARDS group]) and in eight normal anesthetized-paralyzed subjects (control group), we partitioned the total respiratory system mechanics into the lung (L) and chest wall (w) mechanics using the esophageal balloon technique together with the airway occlusion technique during constant flow inflation. We measured lung elastance (Est,L), chest wall elastance (Est,w), and total lung (Rmax, L) and chest wall (Rmax,w) resistance. Rmax,L includes airway (Rmin,L) and "additional" lung resistance (DR,L). DR,L represents the "additional" component due to the viscoelastic phenomena of the lung tissues and time-constant inequalities (pendelluft). Measurements were repeated at 0, 5, and 10 cm H2O of positive end-expiratory pressure (PEEP) in the control group and at 0, 5, 10, and 15 cm H2O PEEP in patients with ALI. The end-expiratory lung volume (EELV) was measured at each level of PEEP. Specific total lung (sRmax,L), airway (sRmin,L), and "additional" lung (sDR,L) resistances were obtained as Rmax,L x EELV, Rmin,L x EELV, and DR,L x EELV, respectively. At PEEP 0 cm H2O, we found that both Est,L (23.7 +/- 5.5 and 13.8 +/- 3.3 versus 9.3 +/- 1.7 cm H2O/L; p < 0.01) and Est,w (13.2 +/- 5.4 and 9.9 +/- 2.1 versus 5.6 +/- 2.3 cm H2O/L; p < 0.01) were markedly increased in patients with ARDS and moderate ALI compared with control subjects, with a significant (p < 0.01) effect of the severity of the disease on Est,L (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Animal studies have suggested that arterial compliance can be modulated by adrenergic influences. Whether this adrenergic modulation also occurs in humans is still a matter of debate. In the present article we address this issue by examining the relationships between sympathetic tone and arterial compliance in a variety of physiological and pathophysiological conditions. We have found that cigarette smoking, ie, an action that produces a marked sympathetic activation, causes a significant reduction in radial artery compliance, as measured by an echotracking device capable of providing continuous beat-to-beat evaluation of this hemodynamic variable. When expressed as compliance index, ie, as the ratio between the area under the compliance-pressure curve and pulse pressure, the reduction amounted to 35.7 +/- 4.8% (mean +/- SEM) and was independent of the smoking-related blood pressure increase. Furthermore, pharmacological stimulation of adrenergic receptors located in the arterial wall was also shown to affect arterial compliance because the radial artery compliance index was markedly reduced (- 29.5 +/- 3.9%) during phenylephrine infusion in the brachial artery at doses devoid of any systemic blood pressure effect. Evidence was also obtained that the relationship between sympathetic activation and arterial compliance has pathophysiological relevance, because in 17 patients with congestive heart failure (New York Heart Association classes II through IV) there was a significant inverse correlation (r = .62, P < .01) between muscle sympathetic nerve activity (directly measured by microneurography in the peroneal nerve) and radial artery compliance.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: We obtained chest computed tomography (CT) sections in 12 normal subjects (controls) and 17 patients with the adult respiratory distress syndrome (ARDS) to investigate regional lung inflation. A basal CT section (just above the diaphragm) was obtained in the supine position at zero cm H2O end-expiratory pressure. In each CT section the distance from ventral to dorsal surface (hT) was divided into 10 equal intervals, and 10 lung levels from ventral (no. 1) to dorsal (no. 10) were defined. Knowing the average density and the volume of each level, we computed: (1) the tissue volume; (2) the gas/tissue (g/t) ratio (index of regional inflation); (3) the hydrostatic pressure superimposed on each level (SPL), estimated as density x height. The total volume of the basal CT section was 49 +/- 2.5 ml x m-2 (mean +/- SE) in control subjects and 43 +/- 2.3 ml x m-2 in patients with ARDS (p = not significant [NS]). The tissue volume, however, was 16.7 +/- 0.8 ml x m-2 in control subjects and 31.6 +/- 1.7 ml x m-2 in patients with ARDS (p < 0.01). The g/t ratio in level 1 averaged 4.7 +/- 0.5 in control subjects and 1.2 +/- 0.2 in patients with ARDS (p < 0.01), and this ratio decreased exponentially from level 1 to level 10, both in controls and patients with ARDS. The Kd constant of the exponential decrease was 13.9 +/- 1.3 cm in control subjects and 7.8 +/- 0.8 cm in patients with ARDS (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: OBJECTIVE--To assess the clinical consequences of duration of adult respiratory distress syndrome (ARDS) on lung structure and function. DESIGN--Retrospective analysis. SETTING--A university hospital referral center for extracorporeal support. PATIENTS--A total of 84 patients with severe ARDS (Murray score > 2.5) recruited from 48 intensive care units (1979 to 1992), who suffered ARDS and underwent mechanical ventilation for up to 1 week (37 patients with early ARDS), between 1 and 2 weeks (24 patients with intermediate ARDS), or more than 2 weeks (23 patients with late ARDS) and subsequently underwent extracorporeal support. MAIN OUTCOME MEASURES--Before beginning extracorporeal support, we measured gas exchange, pulmonary mechanics, hemodynamics, oxygen transport and delivery, incidence of barotrauma (presence of one or more thoracic tubes for pneumothorax drainage), and organ dysfunctions. In a subgroup of 16 patients, we studied lung structure by computed tomographic scan, scoring the densities and quantifying the emphysemalike lesions (bullae). RESULTS--Late ARDS showed lower respiratory compliance, higher dead space, higher PaCO2, lower venous admixture, and lower positive end-expiratory pressure requirement compared with early ARDS (P < .01). The incidence of pneumothorax (48.8% of the entire population) was significantly (P < .01) higher in late ARDS (87%) vs intermediate ARDS (46%) and early ARDS (30%). The mortality of patients with pneumothorax (66%) was significantly (P < .01) higher compared with patients without pneumothorax (46%). The number of bullae per lung was significantly higher in late ARDS vs intermediate and early ARDS (mean [SD], 8 [4], 4.3 [5], and 1.9 [3.9], respectively; P < .01), and they were preferentially distributed in the dependent lung regions. The number of bullae per lung was significantly higher in patients with pneumothorax vs those without pneumothorax (mean [SD], 13.6 [9.8] vs 1.4 [2.1]; P = .007). The mean (SD) duration of ARDS in patients with pneumothorax was 15.3 (10.0) days vs 7.0 (6.6) days in those without pneumothorax (P = .0001). No differences within the three groups were found in computed tomographic scan densities, hemodynamics, and number of organ system dysfunctions. CONCLUSIONS--The lung structure and function changes markedly with ARDS duration, and the late stages may be described as restrictive lung disease with superimposed emphysemalike lesions. Presence of pneumothorax affects survival and appears to be related to the lung structural changes occurring with time.
Abstract: OBJECTIVE--To test the hypothesis that positive end-expiratory pressure (PEEP) prevents the collapse of a given lung region when it is equal to or greater than the hydrostatic pressure superimposed (SPL) to that region. DESIGN--Intervention study with sequential levels of PEEP applied in random order to a cohort of patients with adult respiratory distress syndrome (ARDS). SETTING--Referral center for ARDS in a university hospital. PATIENTS--Ten ARDS patients (with Murray scores > 2.5). INTERVENTION--Basal computed tomographic (CT) section taken at 0, 2, 4, 5, 6, 8, 10, 12, 14, 15, and 20 cm H2O PEEP. MAIN OUTCOME MEASURES--Basal lung CT sections were divided into 10 equal levels from the ventral to dorsal surfaces. In each level SPL was measured from density and height. The inflation of the level was measured as the gas/tissue ratio (g/t); g/t changes with PEEP were defined as the g/t-P curve. The slope of the g/t-P curve was defined as level compliance (ie, the ratio of change in the g/t of the level to the change in pressure). A linear g/t-P curve was the criterion to detect inflation without recruitment (ie, new pulmonary units opening at a given pressure). A biphasic g/t-P curve (change of compliance after an inflection point) was the criterion to detect recruitment. Pflex was defined as the pressure at which the inflection point occurred. RESULTS--The SPL increased from level 1 (ventral) to level 10 (dorsal) (r = .91; P < .01). The number of linear g/t-P curves decreased from level 1 to level 10 (r = .98; P < .01), while the number of biphasic g/t-P curves increased (r = .95; P < .01). The Pflex increased from level 1 to 10 (r = .97; P < .01) and Pflex was similar to SPL (Pflex = 1.05 + 0.9 SPL; r = .75; P < .01). CONCLUSIONS--The increased SPL causes compression atelectasis; this is prevented when PEEP to a given lung region is equal to or greater than the SPL.
Abstract: OBJECTIVE: To study the effects of salbutamol (a selective beta 2-adrenergic receptor agonist) on respiratory mechanics in patients with the adult respiratory distress syndrome (ARDS). DESIGN: Prospective study. SETTING: ICU in a university hospital. PATIENTS: Seven mechanically ventilated, paralyzed ARDS patients. MAIN OUTCOME MEASUREMENTS: Measurements of respiratory system compliance, maximum, and minimum inspiratory resistance (by the end-inspiratory occlusion method during constant flow inflation) were performed at 0, 5, 10 cm H2O positive end-expiratory pressure, both before and at least 30 mins after the start of a continuous iv infusion of salbutamol (15 micrograms/min). Minimum inspiratory resistance represents the ohmic air flow resistance, while maximum inspiratory resistance includes minimum inspiratory resistance plus the effective additional resistance due to stress adaptation and to time constant inhomogeneities. Air flow was measured at the airway connector and tracheal pressure near the central end of the artificial airway. RESULTS: Maximum inspiratory resistance, minimum inspiratory resistance, and additional resistance were higher than the values reported for normal anesthetized subjects. On average, salbutamol caused a decrease in maximum and minimum inspiratory resistances (from 6.48 +/- 2.56 to 4.67 +/- 1.74 and from 4.06 +/- 2.12 to 2.07 +/- 0.95 cm H2O/L/sec, respectively). Positive end-expiratory pressure increased additional resistance, whereas it decreased minimum inspiratory resistance. No interaction was found between positive end-expiratory pressure and salbutamol. Respiratory system compliance was not significantly affected by salbutamol nor by positive end-expiratory pressure. CONCLUSIONS: In ARDS patients, salbutamol decreases the abnormally high airway resistance, by reducing minimum resistance, but has no effect on the effective additional resistance.
Abstract: Long-term extracorporeal support for acute lung failure was introduced in 1972. In the 1970s, much effort was concentrated on technical improvements. However, a multicenter study comparing continuous positive-pressure ventilation and continuous positive-pressure ventilation plus extracorporeal circulation failed to show improvement in survival rates. In the 1980s, new physiopathologic concepts were developed, such as extracorporeal CO2 removal coupled with lung rest. The main complication of the technique was bleeding due to systemic heparinization. However, the technology used in that period was the same as in the 1970s. Recently, technological improvement--such as percutaneous cannulation and surface-heparinized artificial lungs--has allowed clinical performances to improve substantially. "Lung rest" philosophy, coupled with safe technology, may provide a rational basis to test this technique in a randomized fashion for widespread use.
Abstract: We investigated the effects of short-term oxygenation changes upon the neuromuscular respiratory drive (airway occlusion pressure [P0.1]), minute ventilation (VE), and respiratory rate (RR) in 12 acute lung injury patients undergoing pressure support ventilation. We ventilated the patients first at a high level (H1) of oxygenation, then at intermediate (I), at low, and again at the high (H2) level. The H1 and H2 periods showed no differences. In the H1, I, and L periods, PaO2 was 158 +/- 68, 75 +/- 12, and 55 +/- 6 mm Hg, respectively. Decreasing oxygenation caused very significant increases in VE, RR, and P0.1. Differences in RR, VE, and rapid shallow breathing index were significant at step H1 versus I. Changes in P0.1 appeared to be higher when the H1 value was higher than normal. An arterial oxygenation target higher than the generally accepted 60 mm Hg level may decrease both RR and VE.
Abstract: We evaluated the airway occlusion maneuver as a method to estimate respiratory resistance, respiratory elastance and the pressure generated by respiratory muscles in ICU patients breathing in the PSV mode. The airflow was interrupted at selected flows or volumes during inspiration by a computer-driven rapid occlusion pneumatic valve. The airway occlusion was maintained for 2 to 3 s. From the airway pressure tracing we obtained various measurements of pressure. We then computed the pressure generated by the patient's inspiratory muscles. The method was validated by two different approaches in two groups of patients: the Pes and the CMV protocols. We conclude that the airflow interruption method can be used to measure basic respiratory mechanical parameters in PSV patients. The method also offers an opportunity to evaluate Pmusc,aw and the respiratory work performed by the patient.
Abstract: We investigated the effects of positive end-expiratory pressure (PEEP) upon respiratory resistance during mechanical ventilation in 21 subjects anesthetized for surgery (normal subjects) and in 11 patients with the adult respiratory distress syndrome (ARDS). We measured tracheal pressure (Ptr) near the end of the endotracheal tube through a 1.5-mm ID catheter and airflow (V) at 0, 5, and 10 cm H2O PEEP (normal subjects) and at 0, 5, 10, 15, and 20 cm H2O PEEP (patients with ARDS). We computed respiratory system static elastance (Estrs), maximal (Rrsmax) and minimal (Rrsmin) inspiratory resistance by the end-inspiratory occlusion method during constant-flow inflation. Rrsmin represents the ohmic respiratory resistance, whereas Rrsmax is Rrsmin plus the additional respiratory impedance caused by the stress adaptation phenomena of the respiratory system tissues and to time constant inhomogeneities between lung units (pendelluft). The difference (Rrsmax - Rrsmin) has been termed DRrs. We also computed expiratory resistance (Rrsexp) at preselected volume (50% of expiration; Rrsexp50) and flow (0.3 L/s; Rrsexp0.3) using the equation: Rrsexp = (Pelrs(t) - Ptr(t]/Flow(t), where elastic recoil pressure (Pelrs) at time t was computed as:Estrs . V(t) + PEEP, in which V(t) is the volume above end-expiratory volume at time t. We found that (1) at PEEP 0, expiratory resistances (Rrsexp50: 7.38 +/- 1.92 versus 5.35 +/- 1.97 cm H2O.L-1.s) and DRrs (3.08 +/- 1.9 versus 1.66 +/- 0.77 cm H2O.L-1.s) were significantly higher in the ARDS group than in the normal group.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: In 17 patients with adult respiratory distress syndrome, we used data derived from computed tomographic (CT) scan densitometric analysis to validate the value of portable chest roentgenograms in objectively estimating the amount of pulmonary edema. Chest roentgenograms and CT scans were taken in the same ventilatory conditions (apnea at 10 cm H2O of positive end-expiratory pressure [PEEP]); blood gas samples and hemodynamic parameters were collected at the same time. Roentgenographic analysis was undertaken by independent observers using two standardized scoring systems proposed in the literature. CT scan analysis was performed using the CT number frequency distribution and the gas lung volume (measured by helium dilution technique) to estimate quantitatively the lung density, the lung weight, and the percentage of normally aerated and nonaerated tissue. Knowing the mean CT number of the pulmonary parenchyma in a group of normal subjects, we also inferred the ideal lung weight expected in the study population and computed the excess tissue mass as the difference between actual and ideal lung weight. Both the roentgenographic scoring systems showed direct correlation with the pulmonary impairment as detected by CT scan densitometric analysis (CT number, percentage of nonaerated tissue, lung weight, and excess tissue mass; p less than 0.01) and inverse relation with the percentage of normally aerated tissue (p less than 0.01). We also found a relationship between roentgenographic scores and the impairment in gas exchange as detected by shunt fraction (p less than 0.05). We conclude that standardized reading of portable chest roentgenograms by means of scoring tables is a valuable tool in estimating the amount of pulmonary edema in a patient with adult respiratory distress syndrome.
Abstract: Ten patients with parenchymal acute respiratory failure (ARF) underwent computed tomography (CT) scans while in the supine and prone positions. At equal levels of positive end-expiratory pressure, the authors measured the changes of CT density in dorsal and ventral basilar lung regions induced by the change of position as well as alterations of gas exchange. The level of venous admixture did not change with body position. The CT scan image of each lung was fractionated into ten levels from dorsal to ventral, each constituting 10% of the lung height. After measuring each lung fraction, the volume, the average CT number, its frequency distribution, and the expected normal value, we computed the lung tissue mass, the excess tissue mass, and the fraction of normally inflated tissue (excess tissue mass = amount of "tissue," which includes edema, cells, and blood in excess of the expected normal value). We also estimated the superimposed hydrostatic pressure on each lung region. We found that the excess lung tissue mass is independent of position. However, in patients in the supine position, lung CT density increased and regional inflation decreased from ventral to dorsal, suggesting progressive deflation of gas-containing alveoli along the gravity gradient. A similar ventral-dorsal deflation pattern occurred within 10 min in patients in the prone position. We conclude that the lung in patients with ARF behaves like an elastic body with a diffusely increased mass; dependent lung regions are compressed by the pressure of overlying structures.(ABSTRACT TRUNCATED AT 250 WORDS)
Abstract: Bleeding due to systemic heparinization represents the major side effect of extracorporeal respiratory support. In the present animal study, a surface heparinized system (Carmeda Biological Active Surface) was applied to assess the feasibility of prolonged perfusion at low circulating heparin levels. Eight sheep divided into two groups: group A (5 animals) and group B (3 animals) underwent venovenous bypass using a heparin coated surface circuit. The following protocol was used: a) 24 hours at high heparin dose (30 to 100 U/kg/hr with an ACT [activated coagulation time] three to four times normal); b) 24 hours at low heparin dose (3 to 8 U/kg/hr with an ACT within the normal range); c) 24 hours at high heparin dose. Group B animals also received fresh frozen sheep plasma (14 ml/kg/day). During Period b, the clotting times were within baseline range. The bleeding time showed a dramatic decrease after change from a to b (27.9 +/- 3 minutes vs. 10.2 +/- 5.6 minutes). There was a negative relationship between antithrombin III (AT III) and thrombin coagulase time (TC); the latter is considered to be an aspecific indicator of circulating fibrin(ogen) degradation products. Maintaining AT III over 70%, TC changes were only minor. The use of the bioactive heparin surface allowed the performance of a 24 hour bypass, with normal coagulation times, at low circulating heparin levels.
Abstract: Thrombohemorrhagic risk is one of the main limiting factors in extracorporeal circulation. We describe here our experience in managing some life-threatening hematological complications in 58 patients with acute respiratory failure treated with long-term extracorporeal assistance. These patients were studied by clinical and laboratory means to assess questions related to heparin monitoring, coagulation complications and bleeding incidence. We found that two clotting tests, activated partial thromboplastin time (APTT) and activated clotting time (ACT) can be easily used to assess the safety of anticoagulant treatment (therapeutic ranges: APTT from 55 to 95 sec and ACT from 170 to 220 sec). A certain degree of coagulation activation, despite heparin, was indicated by the constant finding of thrombin-antithrombin complexes, while fibrinolytic activation, measured as plasminogen activator activity, was confined to the time of bypass connection and was of no clinical consequence. Platelet function was always impaired without relation to the platelet loss. Disseminated intravascular coagulation (DIC) (13 episodes) and severe bleeding (11 episodes) were major complications. DIC was corrected with a good outcome for 8 of 13 patients, while severe bleeding was correlated with a poor outcome in 8 of the 11 patients, probably because of the severity of the underlying disease.
Abstract: The effects of propofol on cerebral blood flow velocity, cerebrospinal fluid pressure, cerebral perfusion pressure and mean arterial pressure were studied during induction in 25 patients scheduled for elective craniotomy. Premedication consisted of only atropine sulphate 0.007 mg/kg (im) 45 min before induction. Measurements were made or derived at time zero and 1, 2, 3, 4 and 5 min after an induction dose of propofol (2.5 mg/kg). Patients were retrospectively stratified into two groups, according to cerebrospinal pressure basal values: (i) lower than 10 mmHg (10 pts) and (ii) higher than 10 mmHg (15 pts). Cerebral blood flow velocity, measured by transcranial Doppler, fell in all the patients, but the reduction was significant at 1, 2, 3 and 4 min only in the group with high CSF pressure, while it never reached the critical value of 10 cm/s. Cerebrospinal fluid pressure and mean arterial pressure decreased in both groups of patients and the fall reached a statistical significance at 1 and 2 min in the group with higher baseline CSF pressure, only at 1 min: a parallel decrease of CPP was recorded, but it was not significant. Thus propofol decreases CSF pressure without hazardous effects on cerebral blood velocity and on cerebral perfusion pressure and seems to be a suitable anaesthetic agent in controlling high cerebrospinal fluid pressure in neuroanaesthesia.
Abstract: A quantitative analysis was performed of the CT images relative to 7 normal human subjects and to 22 patients affected with ARF (Acute Respiratory Failure). The CT scanner image quality was investigated, and the unit was checked with quality control procedures, in order to assure reliability and reproducibility. In every patient the lung was scanned at 3 different levels--basis, hilum and apex. The frequency distribution of CT numbers was studied. The lung areas were calculated for the different conditions, and the data correlated with functional lung data. A method was then tested to evaluate lung weight; the data obtained did not differ from literature data. All the patients were treated with different positive and expiratory pressure (PEEP). For different PEEP values, the quantitative data from CT analysis were correlated with morphofunctional indices.
Abstract: Pulmonary microvascular occlusive disease has been investigated using balloon occlusive pulmonary angiography in 31 patients with severe adult respiratory distress syndrome (ARDS) of different origins (14 patients with pneumonia, nine with multiple injury, eight with sepsis). Multiple pulmonary artery filling defects (PAFD) were detected in 13 (42%) patients, with a seven (78%) in nine incidence among those with posttraumatic ARDS. The presence of PAFD did not correlate with the severity of the respiratory failure, with the pulmonary hemodynamic alterations (pulmonary hypertension and increased vascular resistance), or with the final outcome (mortality rate was 54% among patients with PAFD and 61% among those with normal angiograms). These findings suggest that widespread pulmonary microthrombosis is a common event in patients with polytrauma and respiratory failure, with an important pathophysiologic role in the onset of posttraumatic ARDS.
Abstract: Twenty-two patients with acute respiratory failure underwent lung computed tomography (CT) and physiological measurements at 5, 10, and 15 cm H2O positive end-expiratory pressure (PEEP) to investigate the relationship between morphology and function. Lung densities were primarily concentrated in the dependent regions. From the frequency distribution of CT numbers (difference in x-ray attenuation between water and lung) and lung gas volume measurements the authors obtained a quantitative estimate of normally inflated, poorly inflated, and non-inflated lung tissue weight. This estimated average lung weight was increased twofold above normal and excess lung weight correlated with the mean pulmonary artery pressure (P less than 0.01). Venous admixture correlated with the non-inflated tissue mass (P less than 0.01). Increasing PEEP caused progressive clearing of radiographic densities and increased the mass of normally inflated tissue (anatomic recruitment), while reducing venous admixture. The cardiac index decreased after increasing PEEP while oxygen delivery was unchanged. The authors conclude that CT scan lung density and oxygen exchange efficiency are correlated; the main effect of augmenting PEEP is to recruit perfused alveolar units that were previously collapsed.
Abstract: The anatomic and physiologic response to positive end-expiratory pressure (PEEP) was investigated using computed tomography (CT) in patients with adult respiratory distress syndrome (ARDS). The lesions (densities) in ARDS are distributed inhomogeneously but tend to concentrate in the dependent regions. The estimated lung weight (by CT scan, quantitative analysis, and lung gas volume measured with helium dilution) is, on the average, 200% higher than expected. Changing the body position from supine to prone causes a change in the density distribution in response to gravitational forces. The main effect of PEEP is to clear the densities through alveolar anatomic recruitment. Anatomic recruitment changes the mechanical characteristics of the lung and parallels the improvement in gas exchange. The effects of PEEP on pulmonary arterial pressure appear to be related to anatomic recruitment.
Abstract: To investigate the relationship between lung anatomy and pulmonary mechanics in acute respiratory failure (ARF), 20 patients with ARF underwent computerized tomography (CT) at 3 levels of positive end-expiratory pressure (PEEP) (5, 10, and 15 cm H2O). The static pressure-volume curve of the total respiratory system and the lung volumes (helium dilution method) were also measured. By knowing the lung volumes and analyzing the CT number frequency distribution, a quantitative estimate of normally aerated, poorly aerated, and nonaerated lung tissue was obtained at each level of PEEP. The recruitment was defined as the percent increase of normally aerated tissue from 5 to 15 cm H2O. We found that the different compliances (starting compliance, inflation compliance, and deflation compliance) were correlated only with the amount of normally aerated tissue present in the range of pressures explored by a given compliance (5 cm H2O for starting compliance and 15 cm H2O for inflation and deflation compliances). No relationship was found between the compliances and the poorly aerated and nonaerated tissue. The specific compliance was in the normal range, whereas the amount of recruitment was related to the ratio of inflation compliance to starting compliance. Our data suggest that (1) the pressure-volume curve parameters in ARF investigate only the residual healthy zones of the lung and do not directly estimate the "amount" of disease (poorly or nonaerated tissue), (2) the pressure-volume curve may allow an estimate of the anatomic recruitment, and (3) the residual normally aerated zones of the ARF lung seem to maintain a normal intrinsic elasticity.
Abstract: The volume/pressure (V/P) curve of the total respiratory system in paralysed patients is drawn assuming that volume changes of the respiratory system (delta V resp) equals volume displacement of the measuring apparatus (delta V syr), usually a supersyringe. However, in 93 VP curves we found that O2 removed from the lung-syringe system during the procedure (proportional to the time) largely exceeds the CO2 added to the lung-syringe system (delta V gas). This results in a net loss of volume from the system (delta V resp less than delta V-syr). Deflation compliance, hysteresis area and ratio are significantly affected by this phenomenon. Inflation compliance is less influenced by delta V gas, partially compensated by the intrapulmonary gas expansion due to the temperature changes. We conclude that the parameters computed on the deflation limb of V/P curve are misleading if proper correction of the volume scale is not introduced.
Abstract: Amiodarone, an antiarrhythmic drug, causes pulmonary fibrosis in some patients during chronic treatment but the mechanism is unknown. We studied the effects of amiodarone on pulmonary biochemistry, morphology and function at doses of 25 and 50 mg/kg/12 hr given to rats by gavage for four weeks. Plasma and pulmonary phospholipids were significantly augmented, 13% and 88% respectively, in the group given amiodarone 50 mg/kg/12 hr compared to pair-fed controls. Typical phospholipidosis-like light and electron microscopic alterations were seen in the lung, their severity related to the extent of biochemical changes induced by amiodarone. Pulmonary function tests revealed mild but not significant changes in O2 and CO2 alveolar exchange efficiency and lung compliance (P-V curve) of treated animals in comparison to pair fed controls. Plasma average concentrations of amiodarone and its main metabolite, desethylamiodarone, after four weeks were 2.46 +/- 0.18 and 0.73 +/- 0.13 micrograms/ml, respectively, in the 50 mg/kg/12 hr group. In the same group amiodarone and desethylamiodarone concentrations in lung were 163 +/- 26 and 569 +/- 153 times higher than those in plasma. A highly significant correlation was found between amiodarone concentrations in plasma and lung and phospholipid content in the lung. A subgroup of animals received amiodarone 50 mg/kg/12 hr for 8 weeks. The pulmonary phospholipidosis-like lesions were similar to those observed after one month of treatment, no fibrosis was evident on light microscopic examination.
Abstract: The application of clinical pharmacological concepts and therapeutic standards in intensive care settings presents particularly difficult problems due to the lack of adequately controlled background information and the highly variable and rapidly evolving clinical conditions where drugs must be administered and their impact evaluated. In this review, an attempt has been made to discuss the available knowledge within the framework of a problem-oriented approach, which appears to provide a more clinically useful insight than a drug-centred review. Following a brief discussion of the scanty data and the most interesting models to which reference can be made from a pharmacokinetic point of view (the burn patient being taken as an example), the review concentrates on the main general intervention strategies in intensive care patients. These are based mainly on non-pharmacological measures (correction of fluid and electrolyte balance, total parenteral nutrition, enteral nutrition, oxygenation and ventilatory management) and are discussed with respect to the specific challenge they present in various clinical conditions and organ failure situations. In addition, 4 major selected clinical conditions where general management criteria and careful use of prophylactic and therapeutic drug treatments must interact to cope with the variety of presentations and problems are reviewed. These include: acute cerebral damage; anti-infective prophylaxis and therapy; cardiovascular emergencies; and problems of haemostasis. Each problem is analysed in such a way as to frame the pharmacological intervention in its broader context of the underlying (established or hypothesised) pathophysiology, with special attention being paid to those methodological issues which allow an appreciation of the degree of reliability of the data and the recommendations which appear to be practiced (often haphazardly) in intensive care units. The thorough review of the published literature provided (up to mid-1986) clearly shows that in this field the quality of randomised controlled and epidemiological studies is rather unsatisfactory. It would be highly beneficial to research and to clinical care if larger multicentric protocols and prospective epidemiological comparative investigations could be carried out to investigate more timely and adequately the variables which determine drug action, and the final outcome in the many subgroups of patients which must be considered in a proper stratification of intensive care unit populations.
Abstract: The antipyretic effect of diclofenac sodium 0.2 mg/kg i.v. was studied prospectively in 10 ICU patients. Patients with renal failure and hypovolaemia were excluded from the study; mean basal temperature (measured by the pulmonary artery thermistor) was 38.92 degrees C +/- 0.413 SD. In 9 of the 10 patients, the temperature fell by more than 0.5 degrees C within 1 h of administration of the drug. A minimum mean of 37.80 degrees C +/- 0.636 SD was obtained by the hour 3; the temperature then remained lower than basal throughout the entire observation period (6 h). Changes in haemodynamics and oxygen consumption were consistent with the reduction in temperature. Changes in renal function were transient and did not require any therapeutic intervention. We conclude that the proposed dosage (in the selected patient population) constitutes effective antipyretic treatment devoid of major side effects.
Abstract: Forty-three patients were entered in an uncontrolled study designed to evaluate extracorporeal membrane lung support in severe acute respiratory failure of parenchymal origin. Most of the metabolic carbon dioxide production was cleared through a low-flow venovenous bypass. To avoid lung injury from conventional mechanical ventilation, the lungs were kept "at rest" (three to five breaths per minute) at a low peak airway pressure of 35 to 45 cm H2O (3.4 to 4.4 kPa). The entry criteria were based on gas exchange under standard ventilatory conditions (expected mortality rate, greater than 90%). Lung function improved in thirty-one patients (72.8%), and 21 patients (48.8%) eventually survived. The mean time on bypass for the survivors was 5.4 +/- 3.5 days. Improvement in lung function, when present, always occurred within 48 hours. Blood loss averaged 1800 +/- 850 mL/d. No major technical accidents occurred in more than 8000 hours of perfusion. Extracorporeal carbon dioxide removal with low-frequency ventilation proved a safe technique, and we suggest it as a valuable tool and an alternative to treating severe acute respiratory failure by conventional means.
Abstract: To investigate the effects of both positive end-expiratory pressure (PEEP) and mean airway pressure (Paw) on gas exchange, we used lung lavage to induce severe respiratory insufficiency in six lambs. The animals were then mechanically ventilated at constant tidal volume, respiratory rate, and inspired O2 fraction. PEEP levels were varied -5, +5 and +10 cm H2O around the pressure (Pflex) corresponding to a major change in slope of the inspiratory limb of the respiratory volume-pressure curve. In each animal the effects of the three PEEP levels were studied at two Paw levels, differing by 5 cm H2O. Increasing Paw significantly improved PaO2 and reduced venous admixture. A 5-cm H2O PEEP increase from +5 to +10 did not affect oxygenation; however, oxygenation was significantly better when PEEP was greater than Pflex. Both PaCO2 and anatomic dead space were higher at higher PEEP, and decreased with increasing Paw. Hence, Paw was a major determinant of oxygenation, although a PEEP greater than Pflex appeared necessary to optimize oxygenation at a constant Paw.
Abstract: A case of acute post-traumatic pulmonary failure was treated by extracorporeal respiratory assist, after conventional therapy had failed. Veno-venous bypass was established, with low extracorporeal blood flow (1.6-2 l min-1), and high exchange surface area membrane lungs (7 m2), according to the technique of low-frequency positive-pressure ventilation with extracorporeal carbon-dioxide removal. After a first disconnection, the evolution of the lung disease necessitated a second surgical procedure, during which a chest tube perforated the patient's right lower, pulmonary lobe. A two-stage right thoracotomy was performed, with the patient connected to the extracorporeal system, and receiving full heparinization. Massive bleeding and severe hypoxia were encountered, but successfully overcome. The patient is now a long-term survivor.
Abstract: Extracorporeal CO2-removal (ECCO2-R) with low-frequency positive-pressure ventilation (LFPPV) may relieve the acutely injured lung from the burden and the risks of excessively high ventilatory minute volumes and airway pressures. It was the purpose of this study to document the evolution of lung function during clinical ECCO2-R with special emphasis on extravascular lung water. ECCO2-R was applied in a 21-year-old female patient suffering from severe post-traumatic infectious adult respiratory distress syndrome. The indication for ECCO2-R was based on the following findings: total static lung compliance 25 cm X cm H2O-1; arterial pO2 50 mm Hg with an inspiratory oxygen concentration of 100%; intrapulmonary right-to-left shunt over 50% of the cardiac output; and extravascular lung water 24 ml X kg-1 (normal 4.5-7 ml X kg-1). ECCO2-R was shown to provide satisfactory conditions for improving the above-mentioned abnormal parameters of pulmonary function. Pressure-limited low-frequency mechanical ventilation allowed successful management of several pneumothoraces with bronchopleural fistulas which occurred during the procedure. It is concluded that these complications of positive airway pressure would have led to the patient's death under the conditions of conventional mechanical ventilation.
Abstract: Tracheal and alveolar gas composition was studied by mass spectrometry in a patient with severe ARDS treated by low frequency positive pressure ventilation/extracorporeal CO2-removal (LFPPV-ECCO2R). Measured alveolar gas concentrations were compared with values derived from standard respiratory equations. As a result we found that during LFPPV-ECCO2R with a constant endotracheal O2-flow, alveolar gas composition cannot be predicted reliably from standard equations. The reasons for this finding are discussed. We conclude that monitoring of alveolar gas composition by mass spectrometry is of great value during LFPPV-ECCO2R if PAO2, P(A-a)O2 and Qva/Qt are to be determined correctly.
Abstract: Twenty-one ARDS patients were divided into two groups of severity according to FIO2 and PEEP required to maintain an adequate gas exchange. The 10 most severe patients (group A) underwent continuous positive pressure ventilation (CPPV) (I/E 3:1) with the mean airway pressure maintained at 21 +/- 6.2 cmH2O. The PEEP values were 12.6 +/- 4.3 cmH2O during CPPV and 6.5 +/- 3.7 cmH2O during IRV (p less than 0.01). Eleven less severe ARDS patients (group B) underwent CPPV and positive pressure spontaneous breathing (CPAP) at constant mean airway pressure of 14.3 +/- 3.8 cmH2O. The PEEP was 7 +/- 2.5 cmH2O during CPPV and 14.9 +/- 4.3 cmH2O during CPAP (p less than 0.001). In five patients of each group, the SF6 shunt was measured as representative of true shunt. The results showed that gas exchange, including true shunt, and haemodynamics did not change between CPPV and IRV and between CPPV and CPAP tests. Taken with previous work on mean airway pressure, our results further support the concept that the main determinant of oxygenation and haemodynamics is the mean airway pressure, irrespective of the PEEP level and of the mode of ventilation.
Abstract: A group of 36 patients with severe adult respiratory distress syndrome (ARDS) meeting previously established blood gas criteria (mortality rate 90%) became candidates for possible extracorporeal respiratory support [low frequency positive pressure ventilation with extracorporeal CO2 removal (LFPPV-ECCO2R)]. Before connecting the patients to bypass we first switched the patients from conventional mechanical ventilation with positive end expiratory pressure (PEEP) to pressure controlled inverted ratio ventilation (PC-IRV), and then when feasible, to spontaneous breathing with continuous positive airways pressure (CPAP). Forty eight hours after the patients had entered the treatment protocol, only 19 out of the 36 patients in fact required LFPPV-ECCO2R, while 5 were still on PC-IRV, and 12 were on CPAP. The overall mortality rate of the entire population was 23%. The only predictive value of success or failure of a particular treatment mode was total static lung compliance (TSLC). No patients with a TSLC lower than 25 ml (cm H2O)-1 tolerated either PC-IRV or CPAP, while all patients with a TSLC higher than 30 ml (cm H2O)-1 were successfully treated with CPAP. Borderline patients (TSLC between 25 and 30 ml (cm H2O)-1) had to be treated with PC-IRV for more than 48 h, or were then placed on LFPPV-ECCO2R if Paco2 rose prohibitively. We conclude that TSLC is a most useful measurement in deciding on the best management of patients with severe ARDS, unresponsive to conventional treatment.
Abstract: Factors influencing nitrogen balance during total parenteral nutrition have been investigated in 34 critically ill injured patients studied during the first 6 days after trauma. Basal nitrogen balance was severely negative (-0.26 +/- 0.12 (SD) g X kg-1), but improved consistently during treatment. Nitrogen intake proved to be the major determinant of a positive, or less negative, nitrogen balance, only secondarily followed by total energy intake corrected to predicted basal energy expenditure, according to multiple regression analysis. The amount of non-protein calories and the non-protein calorie to nitrogen ratio appeared to have little significance on nitrogen balance, when corrected for the two former variables.
Abstract: Venous admixture (Qva/Q) in ARF patients is due to both true right to left shunt (Qs/Qt: perfusion of truly unventilated areas) and to maldistribution [Qva-Qs)/Qt: effects of unevenness of ventilation/perfusion ratio). Using the retention rate of sulphur hexafluoride we determined the effects of PEEP on Qs/Qt and (Qva-Qs)/Qt at a constant FIO2 for each patient (0.57 +/- 0.19 SD, range 0.4-0.95). Eleven patients with ARF (treated either by CPPV or CPAP) were studied on 16 occasions. Each measurement was repeated at two levels of PEEP, 5 cm H2O below and 5 cm H2O above the patient's clinically determined PEEP level. The increase in PEEP resulted in: - a decrease in Qva/Q (from 0.37 +/- 0.13 to 0.27 +/- 0.12, p less than 0.01); - a parallel decrease in Qs/Qt (from 0.29 +/- 0.16 to 0.22 +/- 0.14, p less than 0.01); there was a positive correlation between Qva/Q and Qs/Qt changes (r = 0.53, p less than 0.05). No significant variation was demonstrated in (Qva-Qs)/Qt (from 0.074 +/- 0.045 to 0.054 +/- 0.048). On the other hand there was a negative correlation between the fraction of Qva/Q due to the maldistribution and FIO2: (Qva-Qs)/Qva = 0.75-0.86 FIO2 (r = 0.74, p less than 0.01). We conclude that: PEEP decreased Qva/Q mainly through changes in Qs/Qt but did not have a definite effect on (Qva-Qs)/Qt. Maldistribution was responsible for a significant portion of Qva/Q in those ARF patients tolerating a relatively low FIO2 (0.4-0.6).
Abstract: We have explored change in pulmonary compliance before, and after, repeated deep insufflation of the lungs to a pressure of 35 cm H2O, in 130-days gestation fetal lambs delivered by cesarean section, and while still connected to the intact umbilical cord and the ewe. As a group, all 15 out of 28 fetal lambs that had a rise in total compliance to above 0.2 ml (cm H2O)-1 kg-1 after the first inflation, tolerated 24 h of mechanical ventilation with excellent health and good lung function; only 3 animals out of 13 that showed no similar initial rise in compliance after the first inflation, ultimately survived. We believe the first deep insufflation is an important therapeutic intervention and a useful index to rapidly assess chance of survival in a high-risk fetal lamb population.
Abstract: Hyaline membrane disease is found only in lungs where pulmonary ventilation has been established, i.e. after birth. We delivered eleven fetal lambs of a gestational age of 128-130 days but instead kept their lungs in total apnea and inflated to constant pressure, while removing all metabolically produced carbon dioxide with an extracorporeal membrane lung. Oxygen was provided by the membrane lung, and by apneic oxygenation through the natural lungs. Hence, arterial blood gases remained always normal, without any pulmonary ventilation. After 6-66 h the lungs had sufficiently cleared to allow normal mechanical pulmonary ventilation in 10 our of 11 lambs so treated. In a control group treated with mechanical ventilation alone, five of seven lambs died within the first 24 h of severe hyaline membrane disease.
Abstract: Differentiating Qs/Qt over Qva/Q (as measured by the standard O2 content formula) appears to be of great interest in applying and evaluating different therapeutic approaches. The estimation of Qs/Qt by 100% O2 breathing may alter "per se" the lung condition and is unsatisfactory. We used Sulphur Hexafluoride (SF6; lambda = 6.10(-3) ml ml-1 760 mmHg-1) to identify the true shunt (VA/Q less than 0.05) at maintenance F1O2. A simple and rapid determination of SF6 retention is performed by ECD gas chromatography from contemporaneous arterial and mixed venous blood samples, taken during i.v. infusion of an SF6 containing solution. QS/Qt estimate is then given by the ratio: PaSF6/PvSF6. It is not necessary to know the absolute gas partial pressures or concentration, hence absolute gas calibrations are not required. This method is suggested as feasible and satisfactory for clinical use, allowing the determination of QS/Qt at the maintenance F1O2.
Abstract: PGI2 plus very low dose of heparin was infused in 6 lambs connected for long term extracorporeal circulation with a membrane lung. Hemodynamic and hemostasis parameters were compared to those of a control group treated only with standard doses of heparin. PGI2 efficacy in inhibiting platelet aggregation and platelet fall was confirmed. A small platelet release, measured as antiheparin activity, was observed during all the by-pass, but did not influence platelet capacity of recovering when PGI2 effect dissolved. Heparin needed resulted less than a quarter of the quantity used for the control group. In our experimental conditions the hemodynamic changes were mainly limited to a decrease in diastolic blood pressure.
Abstract: Terminal respiratory failure was reversed in three patients with a combination of extra-corporeal CO2 removal through a membrane lung and oxygen diffusion into the diseased lungs between mechanical breaths induced at a frequency of 2-3/min. The technique seems to prevent the pulmonary barotrauma and extrapulmonary derangements caused by conventional mechanical ventilation.
Abstract: Intensive care was applied in 13 patients with acute liver insufficiency and different degrees of metabolic encephalopathy due to the ingestion of Amanita phalloides. Twelve of them were subjected to hepatic assist with E.T., in three cases this measure was repeated. Ten recoveries were obtained, which denote, on the basis of the necrosis enzymes and the hepatic histo-pathological aspects from bioptic samplings, the use of the E.T. method, when applied within the first 72 hours. In pigs poisoned with Amanita phalloides, the clinico-biochemical pattern and the histopathological findings are comparable to the observations in man. Electron microscopy demonstrates peculiar lesion in the cytoplasm. The anatomo-pathological findings in the three dead patients show a liver necrosis over the 90% and the presence of cerebral edema.
