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Biomedical subjects

V Marco Ranieri

Publications and source records attributed to V Marco Ranieri.

At least 19 recordsLinked to original sources

Tidal hyperinflation during low tidal volume ventilation in acute respiratory distress syndrome.

RATIONALE: Tidal volume and plateau pressure limitation decreases mortality in acute respiratory distress syndrome. Computed tomography demonstrated a small, normally aerated compartment on the top of poorly aerated and nonaerated compartments that may be hyperinflated by tidal inflation. OBJECTIVES: We hypothesized that despite tidal volume and plateau pressure limitation, patients with a larger nonaerated compartment are exposed to tidal hyperinflation of the normally aerated compartment. MEASUREMENTS AND MAIN RESULTS: Pulmonary computed tomography at end-expiration and end-inspiration was obtained in 30 patients ventilated with a low tidal volume (6 ml/kg predicted body weight). Cluster analysis identified 20 patients in whom tidal inflation occurred largely in the normally aerated compartment (69.9 +/- 6.9%; "more protected"), and 10 patients in whom tidal inflation occurred largely within the hyperinflated compartments (63.0 +/- 12.7%; "less protected"). The nonaerated compartment was smaller and the normally aerated compartment was larger in the more protected patients than in the less protected patients (p = 0.01). Pulmonary cytokines were lower in the more protected patients than in the less protected patients (p < 0.05). Ventilator-free days were 7 +/- 8 and 1 +/- 2 d in the more protected and less protected patients, respectively (p = 0.01). Plateau pressure ranged between 25 and 26 cm H(2)O in the more protected patients and between 28 and 30 cm H(2)O in the less protected patients (p = 0.006). CONCLUSIONS: Limiting tidal volume to 6 ml/kg predicted body weight and plateau pressure to 30 cm H(2)O may not be sufficient in patients characterized by a larger nonaerated compartment.

Aged↗

Lung recruitment in patients with the acute respiratory distress syndrome.

BACKGROUND: In the acute respiratory distress syndrome (ARDS), positive end-expiratory pressure (PEEP) may decrease ventilator-induced lung injury by keeping lung regions open that otherwise would be collapsed. Since the effects of PEEP probably depend on the recruitability of lung tissue, we conducted a study to examine the relationship between the percentage of potentially recruitable lung, as indicated by computed tomography (CT), and the clinical and physiological effects of PEEP. METHODS: Sixty-eight patients with acute lung injury or ARDS underwent whole-lung CT during breath-holding sessions at airway pressures of 5, 15, and 45 cm of water. The percentage of potentially recruitable lung was defined as the proportion of lung tissue in which aeration was restored at airway pressures between 5 and 45 cm of water. RESULTS: The percentage of potentially recruitable lung varied widely in the population, accounting for a mean (+/-SD) of 13+/-11 percent of the lung weight, and was highly correlated with the percentage of lung tissue in which aeration was maintained after the application of PEEP (r2=0.72, P<0.001). On average, 24 percent of the lung could not be recruited. Patients with a higher percentage of potentially recruitable lung (greater than the median value of 9 percent) had greater total lung weights (P<0.001), poorer oxygenation (defined as a ratio of partial pressure of arterial oxygen to fraction of inspired oxygen) (P<0.001) and respiratory-system compliance (P=0.002), higher levels of dead space (P=0.002), and higher rates of death (P=0.02) than patients with a lower percentage of potentially recruitable lung. The combined physiological variables predicted, with a sensitivity of 71 percent and a specificity of 59 percent, whether a patient's proportion of potentially recruitable lung was higher or lower than the median. CONCLUSIONS: In ARDS, the percentage of potentially recruitable lung is extremely variable and is strongly associated with the response to PEEP.

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Ischemia and reperfusion increases susceptibility to ventilator-induced lung injury in rats.

OBJECTIVES: Hemorrhagic shock followed by resuscitation (HSR) commonly triggers an inflammatory response that leads to acute respiratory distress syndrome. HYPOTHESIS: HSR exacerbates mechanical stress-induced lung injury by rendering the lung more susceptible to ventilator-induced lung injury. METHODS: Rats were subjected to HSR, and were randomized into an HSR + high tidal volume and zero positive end-expiratory pressure (PEEP) or a HSR + low tidal volume with 5 cm H(2)O PEEP. A sham-operated rat + high tidal volume and zero PEEP served as a control. RESULTS: HSR increased susceptibility to ventilator-induced lung injury as evidenced by an increase in lung elastance and the wet/dry ratio and a reduction in Pa(O(2)) as compared with the other groups. The lung injury observed in the HSR + high tidal volume group was associated with a higher level of interleukin 6 in the lung and blood, increased epithelial cell apoptosis in the kidney and small intestine villi, and a tendency toward high levels of alanine aminotransferase, aspartate aminotransferase, lactate dehydrogenase, and creatinine in plasma. CONCLUSIONS: HSR priming renders the lung and kidney more susceptible to mechanical ventilation-induced organ injury.

Alanine Transaminase↗

An evaluation of systemic inflammatory response syndrome signs in the Sepsis Occurrence In Acutely Ill Patients (SOAP) study.

OBJECTIVE: To define the frequency and prognostic implications of SIRS criteria in critically ill patients hospitalized in European ICUs. DESIGN AND SETTING: Cohort, multicentre, observational study of 198 ICUs in 24 European countries. PATIENTS AND INTERVENTIONS: All 3,147 new adult admissions to participating ICUs between 1 and 15 May 2002 were included. Data were collected prospectively, with common SIRS criteria. RESULTS: During the ICU stay 93% of patients had at least two SIRS criteria [respiratory rate (82%), heart rate (80%)]. The frequency of having three or four SIRS criteria vs. two was higher in infected than non-infected patients (p < 0.01). In non-infected patients having more than two SIRS criteria was associated with a higher risk of subsequent development of severe sepsis (odds ratio 2.6, p < 0.01) and septic shock (odds ratio 3.7, p < 0.01). Organ system failure and mortality increased as the number of SIRS criteria increased. CONCLUSIONS: Although common in the ICU, SIRS has prognostic importance in predicting infections, severity of disease, organ failure and outcome.

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Lack of phosphoinositide 3-kinase-gamma attenuates ventilator-induced lung injury.

OBJECTIVE: G protein-coupled receptors may up-regulate the inflammatory response elicited by ventilator-induced lung injury but also regulate cell survival via protein kinase B (Akt) and extracellular signal regulated kinases 1/2 (ERK1/2). The G protein-sensitive phosphoinositide-3-kinase gamma (PI3Kgamma) regulates several cellular functions including inflammation and cell survival. We explored the role of PI3Kgamma on ventilator-induced lung injury. DESIGN: Prospective, randomized, experimental study. SETTING: University animal research laboratory. SUBJECTS: Wild-type (PI3Kgamma), knock-out (PI3Kgamma ), and kinase-dead (PI3Kgamma) mice. INTERVENTIONS: Three ventilatory strategies (no stretch, low stretch, high stretch) were studied in an isolated, nonperfused model of acute lung injury (lung lavage) in PI3Kgamma, PI3Kgamma, and PI3Kgamma mice. MEASUREMENTS AND MAIN RESULTS: Reduction in lung compliance, hyaline membrane formation, and epithelial detachment with high stretch were more pronounced in PI3Kgamma than in PI3Kgamma and PI3Kgamma (p < .01). Inflammatory cytokines and IkBalpha phosphorylation with high stretch did not differ among PI3Kgamma, PI3Kgamma, and PI3Kgamma. Apoptotic index (terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling) and caspase-3 (immunohistochemistry) with high stretch were larger (p < .01) in PI3Kgamma and PI3Kgamma than in PI3Kgamma. Electron microscopy showed that high stretch caused apoptotic changes in alveolar cells of PI3Kgamma mice whereas PI3Kgamma mice showed necrosis. Phosphorylation of Akt and ERK1/2 with high stretch was more pronounced in PI3Kgamma than in PI3Kgamma and PI3Kgamma (p < .01). CONCLUSIONS: Silencing PI3Kgamma seems to attenuate functional and morphological consequences of ventilator-induced lung injury independently of inhibitory effects on cytokines release but through the enhancement of pulmonary apoptosis.

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Sepsis in European intensive care units: results of the SOAP study.

OBJECTIVE: To better define the incidence of sepsis and the characteristics of critically ill patients in European intensive care units. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight intensive care units in 24 European countries. PATIENTS: All new adult admissions to a participating intensive care unit between May 1 and 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Demographic data, comorbid diseases, and clinical and laboratory data were collected prospectively. Patients were followed up until death, until hospital discharge, or for 60 days. Of 3,147 adult patients, with a median age of 64 yrs, 1,177 (37.4%) had sepsis; 777 (24.7%) of these patients had sepsis on admission. In patients with sepsis, the lung was the most common site of infection (68%), followed by the abdomen (22%). Cultures were positive in 60% of the patients with sepsis. The most common organisms were Staphylococcus aureus (30%, including 14% methicillin-resistant), Pseudomonas species (14%), and Escherichia coli (13%). Pseudomonas species was the only microorganism independently associated with increased mortality rates. Patients with sepsis had more severe organ dysfunction, longer intensive care unit and hospital lengths of stay, and higher mortality rate than patients without sepsis. In patients with sepsis, age, positive fluid balance, septic shock, cancer, and medical admission were the important prognostic variables for intensive care unit mortality. There was considerable variation between countries, with a strong correlation between the frequency of sepsis and the intensive care unit mortality rates in each of these countries. CONCLUSIONS: This large pan-European study documents the high frequency of sepsis in critically ill patients and shows a close relationship between the proportion of patients with sepsis and the intensive care unit mortality in the various countries. In addition to age, a positive fluid balance was among the strongest prognostic factors for death. Patients with intensive care unit acquired sepsis have a worse outcome despite similar severity scores on intensive care unit admission.

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Does dopamine administration in shock influence outcome? Results of the Sepsis Occurrence in Acutely Ill Patients (SOAP) Study.

OBJECTIVE: The optimal adrenergic support in shock is controversial. We investigated whether dopamine administration influences the outcome from shock. DESIGN: Cohort, multiple-center, observational study. SETTING: One hundred and ninety-eight European intensive care units. PATIENTS: All adult patients admitted to a participating intensive care unit between May 1 and May 15, 2002. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients were followed up until death, until hospital discharge, or for 60 days. Shock was defined as hemodynamic compromise necessitating the administration of vasopressor catecholamines. Of 3,147 patients, 1,058 (33.6%) had shock at any time; 462 (14.7%) had septic shock. The intensive care unit mortality rate for shock was 38.3% and 47.4% for septic shock. Of patients in shock, 375 (35.4%) received dopamine (dopamine group) and 683 (64.6%) never received dopamine. Age, gender, Simplified Acute Physiology Score II, and Sequential Organ Failure Assessment score were comparable between the two groups. The dopamine group had higher intensive care unit (42.9% vs. 35.7%, p=.02) and hospital (49.9% vs. 41.7%, p=.01) mortality rates. A Kaplan-Meier survival curve showed diminished 30 day-survival in the dopamine group (log rank=4.6, p=.032). In a multivariate analysis with intensive care unit outcome as the dependent factor, age, cancer, medical admissions, higher mean Sequential Organ Failure Assessment score, higher mean fluid balance, and dopamine administration were independent risk factors for intensive care unit mortality in patients with shock. CONCLUSIONS: This observational study suggests that dopamine administration may be associated with increased mortality rates in shock. There is a need for a prospective study comparing dopamine with other catecholamines in the management of circulatory shock.

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Is albumin administration in the acutely ill associated with increased mortality? Results of the SOAP study.

INTRODUCTION: Albumin administration in the critically ill has been the subject of some controversy. We investigated the use of albumin solutions in European intensive care units (ICUs) and its relationship to outcome. METHODS: In a cohort, multicenter, observational study, all patients admitted to one of the participating ICUs between 1 May and 15 May 2002 were followed up until death, hospital discharge, or for 60 days. Patients were classified according to whether or not they received albumin at any time during their ICU stay. RESULTS: Of 3,147 admitted patients, 354 (11.2%) received albumin and 2,793 (88.8%) did not. Patients who received albumin were more likely to have cancer or liver cirrhosis, to be surgical admissions, and to have sepsis. They had a longer length of ICU stay and a higher mortality rate, but were also more severely ill, as manifested by higher simplified acute physiology score (SAPS) II and sequential organ failure assessment (SOFA) scores than the other patients. A Cox proportional hazard model indicated that albumin administration was significantly associated with decreased 30-day survival. Moreover, in 339 pairs matched according to a propensity score, ICU and hospital mortality rates were higher in the patients who had received albumin than in those who had not (34.8 versus 20.9% and 41.3 versus 27.7%, respectively, both p < 0.001). CONCLUSION: Albumin administration was associated with decreased survival in this population of acutely ill patients. Further prospective randomized controlled trials are needed to examine the effects of albumin administration in sub-groups of acutely ill patients.

Age Distribution↗

Effectiveness of mask and helmet interfaces to deliver noninvasive ventilation in a human model of resistive breathing.

The helmet, a transparent latex-free polyvinyl chloride cylinder linked by a metallic ring to a soft collar that seals the helmet around the neck, has been recently proposed as an effective alternative to conventional face mask to deliver pressure support ventilation (PSV) during noninvasive ventilation in patients with acute respiratory failure. We tested the hypothesis that mechanical characteristics of the helmet (large internal volume and high compliance) might impair patient-ventilator interactions compared with standard face mask. Breathing pattern, CO(2) clearance, indexes of inspiratory muscle effort and patient-ventilator asynchrony, and dyspnea were measured at different levels of PSV delivered by face mask and helmet in six healthy volunteers before (load-off) and after (load-on) application of a linear resistor. During load-off, no differences in breathing pattern and inspiratory muscle effort were found. During load-on, the use of helmet to deliver pressure support increased inspiratory muscle effort and patient-ventilator asynchrony, worsened CO(2) clearance, and increased dyspnea compared with standard face mask. Autocycled breaths accounted for 12 and 25% of the total minute ventilation and for 10 and 23% of the total inspiratory muscle effort during mask and helmet PSV, respectively. We conclude that PSV delivered by helmet interface is less effective in unloading inspiratory muscles compared with PSV delivered by standard face mask. Other ventilatory assist modes should be tested to exploit to the most the potential benefits offered by the helmet.

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Continuous positive airway pressure for treatment of postoperative hypoxemia: a randomized controlled trial.

CONTEXT: Hypoxemia complicates the recovery of 30% to 50% of patients after abdominal surgery; endotracheal intubation and mechanical ventilation may be required in 8% to 10% of cases, increasing morbidity and mortality and prolonging intensive care unit and hospital stay. OBJECTIVE: To determine the effectiveness of continuous positive airway pressure compared with standard treatment in preventing the need for intubation and mechanical ventilation in patients who develop acute hypoxemia after elective major abdominal surgery. DESIGN AND SETTING: Randomized, controlled, unblinded study with concealed allocation conducted between June 2002 and November 2003 at 15 intensive care units of the Piedmont Intensive Care Units Network in Italy. PATIENTS: Consecutive patients who developed severe hypoxemia after major elective abdominal surgery. The trial was stopped for efficacy after 209 patients had been enrolled. INTERVENTIONS: Patients were randomly assigned to receive oxygen (n = 104) or oxygen plus continuous positive airway pressure (n = 105). MAIN OUTCOME MEASURES: The primary end point was incidence of endotracheal intubation; secondary end points were intensive care unit and hospital lengths of stay, incidence of pneumonia, infection and sepsis, and hospital mortality. RESULTS: Patients who received oxygen plus continuous positive airway pressure had a lower intubation rate (1% vs 10%; P = .005; relative risk [RR], 0.099; 95% confidence interval [CI], 0.01-0.76) and had a lower occurrence rate of pneumonia (2% vs 10%, RR, 0.19; 95% CI, 0.04-0.88; P = .02), infection (3% vs 10%, RR, 0.27; 95% CI, 0.07-0.94; P = .03), and sepsis (2% vs 9%; RR, 0.22; 95% CI, 0.04-0.99; P = .03) than did patients treated with oxygen alone. Patients who received oxygen plus continuous positive airway pressure also spent fewer mean (SD) days in the intensive care unit (1.4 [1.6] vs 2.6 [4.2], P = .09) than patients treated with oxygen alone. The treatments did not affect the mean (SD) days that patients spent in the hospital (15 [13] vs 17 [15], respectively; P = .10). None of those treated with oxygen plus continuous positive airway pressure died in the hospital while 3 deaths occurred among those treated with oxygen alone (P = .12). CONCLUSION: Continuous positive airway pressure may decrease the incidence of endotracheal intubation and other severe complications in patients who develop hypoxemia after elective major abdominal surgery.

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Mechanical ventilation affects inflammatory mediators in patients undergoing cardiopulmonary bypass for cardiac surgery: a randomized clinical trial.

OBJECTIVES: Respiratory support for patients recovering from cardiopulmonary bypass and cardiac surgery uses large tidal volumes and a minimal level of positive end-expiratory pressure. Recent data indicate that these ventilator settings might cause pulmonary and systemic inflammation in patients with acute lung injury. We examined the hypothesis that high tidal volumes and low levels of positive end-expiratory pressure might worsen the inflammatory response associated to cardiopulmonary bypass. METHODS: Forty patients undergoing elective coronary artery bypass were randomized to be ventilated after cardiopulmonary bypass disconnection with high tidal volume/low positive end-expiratory pressure (10-12 mL/kg and 2-3 cm H2O, respectively) or low tidal volume/high positive end-expiratory pressure (8 mL/kg and 10 cm H2O, respectively). Interleukin 6 and interleukin 8 levels were measured in the bronchoalveolar lavage fluid and plasma. Samples were taken before sternotomy (time 0), immediately after cardiopulmonary bypass separation (time 1), and after 6 hours of mechanical ventilation (time 2). RESULTS: Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and plasma significantly increased at time 1 in both groups but further increased at time 2 only in patients ventilated with high tidal volume/low positive end-expiratory pressure. Interleukin 6 and interleukin 8 levels in the bronchoalveolar lavage fluid and in the plasma at time 2 were higher with high tidal volume/low positive end-expiratory pressure than with low tidal volume/high positive end-expiratory pressure. CONCLUSION: Mechanical ventilation might be a cofactor able to influence the inflammatory response after cardiac surgery.

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Patient-ventilator interaction during the triggering phase.

Partial patient-controlled mechanical support mode ventilators provide positive pressure assistance whenever a patient's inspiratory effort decreases pressure or flow in the ventilator circuit below the sensitivity set by clinicians; these modes minimize disuse atrophy of the respiratory muscles, can facilitate the weaning process, and usually require lower ventilator pressures. The capability of restoring gas exchange, unloading respiratory muscles, and relieving the patient's dyspnea with partial patient-controlled mechanical support modes depends on matching between the ventilator setting and the patient's ventilatory demand (ie, patient-ventilator interactions).

Airway Resistance↗

Overview of ventilator-induced lung injury mechanisms.

PURPOSE OF REVIEW: Mechanical ventilation is the main supportive therapy for patients with acute respiratory distress syndrome. As with any therapy, mechanical ventilation has side effects and may induce lung injury. This review will focus on stretch-dependent activation of alveolar epithelial and endothelial cells and polymorphonuclear leukocytes, and apoptosis/necrosis balance. RECENT FINDINGS: The past year has seen important research in the area of mechanotransduction and lung native immunity, suggesting further mechanisms of lung inflammation and injury in ventilator-induced lung injury. Research in the past year has also stressed the importance of inflammatory response by alveolar cells and role of polymorphonuclear leukocytes in stretch-induced lung injury and has suggested a role for apoptosis in the maintenance of the alveolar epithelium. SUMMARY: The proportion of patients receiving protective ventilatory strategies remains modest. If efforts to minimize the iatrogenic consequences of mechanical ventilation are to succeed, there must be a greater understanding of the signal transduction mechanisms and the development of potential pharmacologic targets to modulate the molecular and cellular effects of lung stretch.

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Acute respiratory distress syndrome: update on the latest developments in basic and clinical research.

PURPOSE OF REVIEW: Acute lung injury/acute respiratory distress syndrome is a common, serious condition affecting a heterogeneous population of critically ill patients. Other than low tidal volume ventilation, no specific therapy has improved survival. Understanding the epidemiology, pathogenesis, and lessons to be learned from previous clinical trials is necessary for the development of new therapies and the rational design of studies assessing their efficacy. RECENT FINDINGS: Acute lung injury/acute respiratory distress syndrome occurs in 6-8% of the general intensive care unit population, with a mortality of 32-45%. A recent epidemiologic study found that multi-organ dysfunction, use of tidal volumes higher than 6 ml/kg, and high mean fluid balance were independent risks for mortality. Although high levels of inflammatory mediators are also markers for acute respiratory distress syndrome development and death, short courses of high-dose steroids are not effective in acute cases. The latest theory of biotrauma proposes cellular mechanisms by which mechanical ventilation incites a local and systemic inflammatory response; protective lung ventilation with low tidal volumes can attenuate this inflammation and injury to distal organs. Endogenous surfactant function is clearly impaired, but no commercially available surfactant preparation has been shown to reduce mortality. Results of trials to determine efficacy of steroids in late cases and optimal fluid management are pending. SUMMARY: The results of recent clinical trials have raised more questions. Further study of the inflammatory response, surfactant regulation, and the cellular impact of mechanical ventilation should help to develop new therapies, target patients most likely to benefit, and identify appropriate timing of intervention.

Journal Article↗

Incidence and prognosis of intraabdominal hypertension in a mixed population of critically ill patients: a multiple-center epidemiological study.

OBJECTIVE: Intraabdominal hypertension is associated with significant morbidity and mortality in surgical and trauma patients. The aim of this study was to assess, in a mixed population of critically ill patients, whether intraabdominal pressure at admission was an independent predictor for mortality and to evaluate the effects of intraabdominal hypertension on organ functions. DESIGN: Multiple-center, prospective epidemiologic study. SETTING: Fourteen intensive care units in six countries. PATIENTS: A total of 265 consecutive patients admitted for >24 hrs during the 4-wk study period. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Intraabdominal pressure was measured twice daily via the bladder. Data recorded on admission were the patient demographics with Simplified Acute Physiology Score II, Acute Physiology and Chronic Health Evaluation II score, and type of admission; during intensive care stay, Sepsis-Related Organ Failure Assessment score and intraabdominal pressure were measured daily together with fluid balance. Nonsurvivors had a significantly higher mean intraabdominal pressure on admission than survivors: 11.4 +/- 4.8 vs. 9.5 +/- 4.8 mm Hg. Independent predictors for mortality were age (odds ratio, 1.04; 95% confidence interval, 1.01-1.06; p = .003), Acute Physiology and Chronic Health Evaluation II score (odds ratio, 1.1; 95% confidence interval, 1.05-1.15; p < .0001), type of intensive care unit admission (odds ratio, 2.5 medical vs. surgical; 95% confidence interval, 1.24-5.16; p = .01), and the presence of liver dysfunction (odds ratio, 2.5; 95% confidence interval, 1.06-5.8; p = .04). The occurrence of intraabdominal hypertension during the intensive care unit stay was also an independent predictor of mortality (relative risk, 1.85; 95% confidence interval, 1.12-3.06; p = .01). Patients with intraabdominal hypertension at admission had significantly higher Sepsis-Related Organ Failure Assessment scores during the intensive care unit stay than patients without intraabdominal hypertension. CONCLUSIONS: Intraabdominal hypertension on admission was associated with severe organ dysfunction during the intensive care unit stay. The mean intraabdominal pressure on admission was not an independent risk factor for mortality; however, the occurrence of intraabdominal hypertension during the intensive care unit stay was an independent outcome predictor.

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