Guillermo Bugedo

Lung Opening and Closing during Ventilation of Acute Respiratory Distress Syndrome

RATIONALE The effects of high positive end-expiratory pressure (PEEP) strictly depend on lung recruitability, which varies widely during acute respiratory distress syndrome (ARDS). Unfortunately, increasing PEEP may lead to opposing effects on two main factors potentially worsening the lung injury, that is, alveolar strain and intratidal opening and closing, being detrimental (increasing the former) or beneficial (decreasing the latter). OBJECTIVES To investigate how lung recruitability influences alveolar strain and intratidal opening and closing after the application of high PEEP. METHODS We analyzed data from a database of 68 patients with acute lung injury or ARDS who underwent whole-lung computed tomography at 5, 15, and 45 cm H(2)O airway pressure. MEASUREMENTS AND MAIN RESULTS End-inspiratory nonaerated lung tissue was estimated from computed tomography pressure-volume curves. Alveolar strain and opening and closing lung tissue were computed at 5 and 15 cm H(2)O PEEP. In patients with a higher percentage of potentially recruitable lung, the increase in PEEP markedly reduced opening and closing lung tissue (P < 0.001), whereas no differences were observed in patients with a lower percentage of potentially recruitable lung. In contrast, alveolar strain similarly increased in the two groups (P = 0.89). Opening and closing lung tissue was distributed mainly in the dependent and hilar lung regions, and it appeared to be an independent risk factor for death (odds ratio, 1.10 for each 10-g increase). CONCLUSIONS In ARDS, especially in patients with higher lung recruitability, the beneficial impact of reducing intratidal alveolar opening and closing by increasing PEEP prevails over the effects of increasing alveolar strain.

Gut mucosal atrophy after a short enteral fasting period in critically ill patients.

PURPOSE The purpose of this study was to evaluate the presence of gut mucosal atrophy and changes in mucosal permeability in critically ill patients after a short fasting period. MATERIALS AND METHODS Fifteen critically ill patients underwent a period of enteral fasting of at least 4 days (mean 7.8 days). We took the following measurements the day before initiating enteral nutrition: indirect calorimetry, serum albumin, prealbumin, and lymphocyte count. We also performed a duodenal endoscopic biopsy with histopathological and mucosal morphometric analysis including villus height and crypt depth. The lactulose-mannitol test was performed to assess gut permeability. A total of 28 healthy volunteers served as controls for duodenal biopsy or lactulose-mannitol test. Clinical data, such as length of fasting, severity score, and previous parenteral nutritional support, were recorded. RESULTS We found gut mucosal atrophy, expressed as a decrease in villus height and crypt depth, in patients compared with controls. The patients also exhibited an abnormal lactulose-mannitol test. Morphometric changes did not correlate with permeability. Further, we found no correlation between the results of the lactulose-mannitol test and of mucosal morphometry with clinical data. CONCLUSIONS We found that a short period of enteral fasting was associated with significant duodenal mucosal atrophy and abnormal gut permeability in critically ill patients.

Lung Inhomogeneity in Patients with Acute Respiratory Distress Syndrome

RATIONALE Pressures and volumes needed to induce ventilator-induced lung injury in healthy lungs are far greater than those applied in diseased lungs. A possible explanation may be the presence of local inhomogeneities acting as pressure multipliers (stress raisers). OBJECTIVES To quantify lung inhomogeneities in patients with acute respiratory distress syndrome (ARDS). METHODS Retrospective quantitative analysis of CT scan images of 148 patients with ARDS and 100 control subjects. An ideally homogeneous lung would have the same expansion in all regions; lung expansion was measured by CT scan as gas/tissue ratio and lung inhomogeneities were measured as lung regions with lower gas/tissue ratio than their neighboring lung regions. We defined as the extent of lung inhomogeneities the fraction of the lung showing an inflation ratio greater than 95th percentile of the control group (1.61). MEASUREMENTS AND MAIN RESULTS The extent of lung inhomogeneities increased with the severity of ARDS (14 ± 5, 18 ± 8, and 23 ± 10% of lung volume in mild, moderate, and severe ARDS; P < 0.001) and correlated with the physiologic dead space (r(2) = 0.34; P < 0.0001). The application of positive end-expiratory pressure reduced the extent of lung inhomogeneities from 18 ± 8 to 12 ± 7% (P < 0.0001) going from 5 to 45 cm H2O airway pressure. Lung inhomogeneities were greater in nonsurvivor patients than in survivor patients (20 ± 9 vs. 17 ± 7% of lung volume; P = 0.01) and were the only CT scan variable independently associated with mortality at backward logistic regression. CONCLUSIONS Lung inhomogeneities are associated with overall disease severity and mortality. Increasing the airway pressures decreased but did not abolish the extent of lung inhomogeneities.

Renal function and cardiopulmonary bypass : effect of perfusion pressure

Controversy continues as to whether hypotension during cardiopulmonary bypass (CPB) impairs intraoperative and postoperative renal function. Therefore, 21 patients with normal renal function (plasma creatinine less than 1.2 mg/dL, creatinine clearance greater than 70 mL/min), aged 50 to 70 years, without associated pathology, scheduled for elective coronary surgery were studied prospectively. Patients were randomized into two groups: group 1 included 14 patients whose arterial blood pressure during CPB was left untreated, and group 2 consisted of 7 patients who received phenylephrine to maintain their arterial pressure above 70 mmHg. Plasma and urine creatinine, sodium, potassium, and osmolality were measured preoperatively, intraoperatively and postoperatively. Creatinine, osmolal and free water clearances, and excreted sodium fraction were calculated. Plasma creatinine remained normal throughout the study in all patients. Creatinine clearances were similar preoperatively (101.9 +/- 36.7 in group 1 and 120.6 +/- 50.7 mL/min in group 2). In group 1, creatinine clearance decreased during CPB to 88.7 +/- 39.7 mL/min, whereas in group 2 it increased to 157.6 +/- 79.5 mL/min; the difference between groups was significant. Early postoperatively, there was no difference: 136.2 +/- 86.6 mL/min in group 1 and 100 +/- 21.4 mL/min in group 2. One week postoperatively, values were 100.5 +/- 37.9 and 101.9 +/- 18.4, respectively. There was a significant correlation between the creatinine clearance and perfusion pressure intraoperatively, but not postoperatively. Osmolal clearance also correlated with perfusion pressure intraoperatively, but it was significantly lower in the phenylephrine group postoperatively. Postoperative renal function was normal in all patients; no deleterious effect of a low arterial pressure during bypass could be identified.

Anatomical and functional intrapulmonary shunt in acute respiratory distress syndrome

Objectives:The lung-protective strategy employs positive end-expiratory pressure to keep open otherwise collapsed lung regions (anatomical recruitment). Improvement in venous admixture with positive end-expiratory pressure indicates functional recruitment to better gas exchange, which is not necessarily related to anatomical recruitment, because of possible global/regional perfusion modifications. Therefore, we aimed to assess the value of venous admixture (functional shunt) in estimating the fraction of nonaerated lung tissue (anatomical shunt compartment) and to describe their relationship. Design:Retrospective analysis of a previously published study. Setting:Intensive care units of four university hospitals. Patients:Fifty-nine patients with acute lung injury/acute respiratory distress syndrome. Interventions:Positive end-expiratory pressure trial at 5 and 15 cm H2O positive end-expiratory pressures. Measurements and Main Results:Anatomical shunt compartment (whole-lung computed tomography scan) and functional shunt (blood gas analysis) were assessed at 5 and 15 cm H2O positive end-expiratory pressures. Apparent perfusion ratio (perfusion per gram of nonaerated tissue/perfusion per gram of total lung tissue) was defined as the ratio of functional shunt to anatomical shunt compartment. Functional shunt was poorly correlated to the anatomical shunt compartment (r2 = .174). The apparent perfusion ratio at 5 cm H2O positive end-expiratory pressure was widely distributed and averaged 1.25 ± 0.80. The apparent perfusion ratios at 5 and 15 cm H2O positive end-expiratory pressures were highly correlated, with a slope close to identity (y = 1.10·x −0.03, r2 = .759), suggesting unchanged blood flow distribution toward the nonaerated lung tissue, when increasing positive end-expiratory pressure. Conclusions:Functional shunt poorly estimates the anatomical shunt compartment, due to the large variability in apparent perfusion ratio. Changes in anatomical shunt compartment with increasing positive end-expiratory pressure, in each individual patient, may be estimated from changes in functional shunt, only if the anatomical-functional shunt relationship at 5 cm H2O positive end-expiratory pressure is known.

Use of methylene blue in patients with refractory septic shock: Impact on hemodynamics and gas exchange

PURPOSE The purpose of this study was to assess the acute effects of methylene blue, an inhibitor of nitric oxide synthesis, on hemodynamics and gas exchange in patients with refractory septic shock in a prospective clinical trial at medical and surgical intensive care units in a tertiary university hospital. PATIENTS AND METHODS Prospective, sequential study of 10 consecutive patients admitted with severe septic shock of diverse causes and unable to achieve an adequate arterial pressure despite the use of at least two vasoactive drugs. Six of them also developed acute lung injury. All received 1 mg/kg intravenous bolus of methylene blue. Hemodynamic and respiratory parameters were measured at baseline and at 30, 60, 120, and 180 minutes after the bolus injection. RESULTS Systolic, diastolic, mean arterial blood pressure, and systemic vascular resistance increased significantly in all patients, whereas no significant changes were observed in cardiac output, oxygen consumption, or oxygen extraction ratio. Gas exchange remained unaffected in patients with acute lung injury. CONCLUSIONS Methylene blue had an acute vasopressor effect in patients with refractory septic shock, and it was not deleterious on respiratory function.

Intra-abdominal hypertension: Incidence and association with organ dysfunction during early septic shock

PURPOSE The objective of this article is to study the cumulative incidence of intra-abdominal hypertension (IAH) in septic shock (SS) patients during the first 72 hours of intensive care unit (ICU) admission and to determine if the presence and severity of IAH are associated with sepsis morbidity and mortality. MATERIALS AND METHODS Eighty-one consecutive SS patients admitted to a surgical-medical ICU of an academic university hospital (January 2005 to January 2006) were included. Intra-abdominal pressure (IAP) and abdominal perfusion pressure (APP) were measured every 6 h (intermittently) for 72 h. Intra-abdominal pressure was registered as minimal, mean, and maximal values per day, during shock and throughout the study period. Intra-abdominal hypertension was diagnosed if IAP remained 12 mm Hg or higher on 2 consecutive measurements and stratified according to the most recent consensus definition (www.wsacs.org). RESULTS According to maximal and mean IAP values, 67 (82.7%) and 62 (76.5%) of the patients developed IAH during the study period, respectively. Mean IAP values remained stable throughout the study period. Surgical patients had a higher incidence of IAH than medical patients (93% vs 73%, P < .009). Maximal IAPs were normally distributed, with nonsurvivors exhibiting significantly higher IAP levels during shock (survivors, 17.2 +/- 5.3; nonsurvivors, 19.9 +/- 5.6 mm Hg; P < .04). Patients with IAH exhibited significantly lower values of APP and diuresis, higher values of lactate and creatinine, and higher maximal norepinephrine doses, and were more frequently mechanically ventilated (P < .05 for all). Increasing degrees of IAH and the development of the abdominal compartment syndrome were associated with lower APP and higher maximal serum creatinine levels (P < .03 for both). CONCLUSIONS Septic shock patients have a very high incidence of IAH, which seems to be associated with the severity of shock and could be related to the development of organ dysfunctions, particularly renal dysfunction. Intra-abdominal pressure should be routinely monitored during the course of SS.

Método para la evaluación de la confusión en la unidad de cuidados intensivos para el diagnóstico de delírium: adaptación cultural y validación de la versión en idioma español

OBJECTIVE To adapt the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU) for the diagnosis of delirium to the language and culture of Spain and to validate the adapted version. DESIGN Population validation. SETTING Intensive care units in a 600-bed university hospital. PATIENTS We studied 29 critical patients undergoing mechanical ventilation. Mean age was 70 years (range 58-77 years), mean APACHE II score 16 (range 13-21), and mean SOFA score 7 (range 4-8). INTERVENTION Two independent operators applied the Spanish version of the CAM-ICU and a psychiatrist applied the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition-Revised (DSM IV TR). MAIN OUTCOME VARIABLES Concordance (kappa index), internal consistency (Cronbachs alpha), and validity (sensitivity and specificity) of the Spanish version of the CAM-ICU were compared to the DSM IV TR, which is considered the current gold standard. RESULTS The translation and cultural adaptation was carried out in accordance with current international guidelines. A total of 65 assessments were performed in 29 patients. The interobserver concordance was high: kappa statistic 0.91 (95% CI: 0.86-0.96). The internal consistence was adequate: Cronbachs alpha=0.84 (unilateral 95% CI: 0.77). For observer A (a physician), the sensitivity of the Spanish version of the CAM-ICU was 80% and the specificity was 96%. For observer B, (a nurse) the sensitivity was 83% and the specificity was 96%. CONCLUSIONS The Spanish version of the CAM-ICU is a valid, reliable, and reproducible instrument that can be satisfactorily applied to diagnose delirium in Spanish-speaking ICU patients.

Clinical characteristics and outcomes of patients with 2009 influenza A(H1N1) virus infection with respiratory failure requiring mechanical ventilation

PURPOSE The purpose of the study was to describe the clinical characteristics and outcomes of critically ill patients with 2009 influenza A(H1N1). METHODS An observational study of patients with confirmed or probable 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation was performed. RESULTS We studied 96 patients (mean age, 45 [14] years [mean, SD]; 44% female). Shock and acute respiratory distress syndrome were diagnosed during the first 72 hours of admission in 43% and 72% of patients, respectively. Noninvasive positive pressure ventilation was used in 45% of the patients, but failed in 77% of them. Bacterial pneumonia was diagnosed in 33% of cases, 8% during the first week (due to community-acquired microorganisms) and 25% after the first week (due to gram-negative bacilli and resistant gram-positive cocci). Intensive care unit mortality was 50%. Nonsurvivors differed from survivors in the prevalence of cardiovascular, respiratory, and hematologic failure on admission and late pneumonia. Reported causes of death were refractory hypoxia, multiorgan failure, and shock (50%, 38%, and 12% of all causes of death, respectively). CONCLUSIONS Patients with 2009 influenza A(H1N1) and respiratory failure requiring mechanical ventilation often present with clinical criteria of acute respiratory distress syndrome and shock. Bacterial pneumonia is a frequent complication. Mortality is high and is primarily due to refractory hypoxia.

Non-lobar atelectasis generates inflammation and structural alveolar injury in the surrounding healthy tissue during mechanical ventilation

IntroductionWhen alveoli collapse the traction forces exerted on their walls by adjacent expanded units may increase and concentrate. These forces may promote its re-expansion at the expense of potentially injurious stresses at the interface between the collapsed and the expanded units. We developed an experimental model to test the hypothesis that a local non-lobar atelectasis can act as a stress concentrator, contributing to inflammation and structural alveolar injury in the surrounding healthy lung tissue during mechanical ventilation.MethodsA total of 35 rats were anesthetized, paralyzed and mechanically ventilated. Atelectasis was induced by bronchial blocking: after five minutes of stabilization and pre-oxygenation with FIO2 = 1.0, a silicon cylinder blocker was wedged in the terminal bronchial tree. Afterwards, the animals were randomized between two groups: 1) Tidal volume (VT) = 10 ml/kg and positive end-expiratory pressure (PEEP) = 3 cmH2O (VT10/PEEP3); and 2) VT = 20 ml/kg and PEEP = 0 cmH2O (VT20/zero end-expiratory pressure (ZEEP)). The animals were then ventilated during 180 minutes. Three series of experiments were performed: histological (n = 12); tissue cytokines (n = 12); and micro-computed tomography (microCT; n = 2). An additional six, non-ventilated, healthy animals were used as controls.ResultsAtelectasis was successfully induced in the basal region of the lung of 26 out of 29 animals. The microCT of two animals revealed that the volume of the atelectasis was 0.12 and 0.21 cm3. There were more alveolar disruption and neutrophilic infiltration in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. Edema was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in the VT20/ZEEP than VT10/PEEP3 group. The volume-to-surface ratio was higher in the peri-atelectasis region than the corresponding contralateral lung (control) in both groups. We did not find statistical difference in tissue interleukin-1β and cytokine-induced neutrophil chemoattractant-1 between regions.ConclusionsThe present findings suggest that a local non-lobar atelectasis acts as a stress concentrator, generating structural alveolar injury and inflammation in the surrounding lung tissue.