Development Of Multiple Organ System Failure Research Articles

Multiple Segmental Lung Lavages in the Treatment of Secondary Alveolar Proteinosis

SESSION TITLE: Pulmonary Manifestations of Systemic Disease 4 SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Pulmonary alveolar proteinosis (PAP) is characterized by the accumulation of periodic acid-Schiff (PAS)-positive material in the lungs. We present a case of multiple segmental lung lavages (MSLL) in the treatment of secondary PAP where whole-lung lavage (WLL) was precluded due to severe refractory hypoxemia. CASE PRESENTATION: A 34-year-old man with history of myelodysplastic syndrome (MDS) status post allogeneic bone marrow transplant was admitted to the intensive care unit (ICU) due to acute on chronic hypoxemic respiratory failure. He was afebrile, hemodynamically stable, his oxyhemoglobin saturation was 92% on 10L of oxygen via non-rebreather mask, and coarse breath sounds were present bilaterally. He had a history of Mycobacterium avium complex (MAC) pulmonary disease and a recent bone marrow biopsy showed MDS recurrence with positive familial GATA2 mutation. Computer tomography (CT) of the chest showed diffuse bilateral groundglass and interstitial opacities. Except for sputum culture positive for MAC, his infectious workup was negative. He was intubated and mechanically ventilated. A bronchoalveolar lavage demonstrated a milky fluid sample with proteinaceous sediment positive for PAS, suggesting PAP. MonoMac syndrome1 was suspected given his MAC pulmonary infections, MDS/GATA2 mutation, and PAP. With severe refractory hypoxemia, WLL was precluded and MSLL were considered as an alternative. Initially, the right lower lobe was lavaged with sequential instillations of saline 35mL-aliquots until the fluid became clear. Within 24 hours, FiO2 requirements decreased from ~0.8-1.0 to 0.65. Segmental lavages of the left lower lobe, and the right upper and middle lobes were completed within the next 48 hours. Unfortunately, the patient developed multiple organ system failure (MOSF) and his family opted for comfort cares. DISCUSSION: Secondary PAP can be found in association with MonoMac syndrome. This case was a diagnostic and therapeutic challenge due to the patient’s comorbidities, decreased functional status at baseline, and atypical findings for PAP on CT of the chest. MSLL resulted in decreased oxygen requirements; however, the impact of these interventions on the final outcome was lessened by the development of MOSF in this case. CONCLUSIONS: When severe hypoxemia among patient with PAP precludes WLL as a therapeutic intervention, multiple segmental lung lavages could be an alternative treatment option, or a temporizing method allowing clinical improvement prior to WLL. Reference #1: 1.Blood.2011;118:2656-2658 DISCLOSURE: The following authors have nothing to disclose: Gustavo Cortes Puentes, Darlene Nelson, James Utz No Product/Research Disclosure Information

Ventilator-induced lung injury and multiple system organ failure: a critical review of facts and hypotheses.

To review how biotrauma leads to the development of multiple system organ failure (MSOF). Published articles on experimental and clinical studies and review articles in the English language were collected and analyzed. The concept that ventilation strategies using "large" tidal volumes and zero PEEP of injured lungs can enhance injury by the release of inflammatory mediators into the lungs and circulation, a mechanism that has been called biotrauma, is supported by evidence from experimental models ranging from mechanically stressed cell systems, to isolated lungs, intact animals, and humans. Biotrauma may lead to MSOF via spillover of lung-borne inflammatory mediators into the systemic circulation. However, spillover of other agents such as bacteria and soluble proapoptotic factors may also contribute to the onset of MSOF. Other less well studied mechanisms such as peripheral immunosuppression and translocation of bacteria and/or products from the gut may play an important role. Finally, genetic variability is a crucial factor. The development of MSOF is a multifactorial process. Our proposed mechanisms linking mechanical ventilation and MSOF suggest several novel therapeutic approaches. However, it will first be necessary to study the mechanisms described above to delineate more precisely the contribution of each proposed factor, their interrelationships, and their time course. We suggest that scientific advances in immunology may offer novel approaches for prevention of MSOF secondary to ventilator-induced lung injury.

Targeting the gut in shock and organ failure

Multiple organ system failure (MOSF) remains a common cause of morbidity and mortality in intensive care. Despite therapeutic advances in organ system support, the incidence of MOSF remains high, varying from 14 to 38%.1,2 Although the gastrointestinal (GI) and hepatic response to critical illness remains incompletely understood, evidence is accumulating that GI function, particularly splanchnic bed perfusion and intestinal mucosal integrity, occupies a crucial role in the development and perpetuation of MOSF.3-6 The purpose of this review is to provide a brief overview of the role of the gut in the development of MOSF, to describe current monitoring techniques to assess the adequacy of gut perfusion and function, and to analyze the impact of available gut-directed therapies on outcome.

Targeting the gut in shock and organ failure

Multiple organ system failure (MOSF) remains a common cause of morbidity and mortality in intensive care. Despite therapeutic advances in organ system support, the incidence of MOSF remains high, varying from 14 to 38%.1,2 Although the gastrointestinal (GI) and hepatic response to critical illness remains incompletely understood, evidence is accumulating that GI function, particularly splanchnic bed perfusion and intestinal mucosal integrity, occupies a crucial role in the development and perpetuation of MOSF.3-6 The purpose of this review is to provide a brief overview of the role of the gut in the development of MOSF, to describe current monitoring techniques to assess the adequacy of gut perfusion and function, and to analyze the impact of available gut-directed therapies on outcome.

Acute respiratory distress syndrome in trauma patients: ICU mortality and prediction factors.

To study the factors that influence the intensive care unit (ICU) mortality of trauma patients who develop acute respiratory distress syndrome (ARDS) and to evaluate determinants of length of ICU stay among these patients. Study on a prospective cohort of 59 trauma patients that developed ARDS. ICU of a referral trauma center. Fifty-nine patients were included during the study period from 1994 to 1997. The dependent variables studied were the mortality and length of ICU stay. The main independent variables studied included the general severity score APACHE III, the revised trauma and injury severity scores (RTS, ISS), emergency treatment measures, the gas exchange index (PaO2/FIO2) recorded after the onset of ARDS and the development of multiple system organ failure (MSOF). Univariate and multivariate analyses were performed. The mean age of patients was 42.1 +/- 16.7 years, 49 patients (83 %) were male, the mean APACHE III score was 52.7 +/- 33.7 points, the ISS 28.5 +/- 11.4 points and the RTS 8.9 +/- 2.5 points. ICU length of stay was 28.5 +/- 24.5 days and the mortality rate 31.7 % (19 deaths). Mortality was associated with the following: PaO2/FIO2 ratio on the 3rd, 5th and 7th days post-ARDS; high volume of crystalloid/colloid infusion during resuscitation; the APACHE III score; and the development of MSOF According to the multivariate analysis, the mortality of these patients was correlated with the PaO2/FIO2 ratio on the 3rd day of ARDS, the APACHE III score and the development of MSOF. This analysis also showed days on mechanical ventilation to be the only variable that predicted ICU length of stay. The ICU mortality of trauma patients with ARDS is related to the APACHE III score, the gas exchange evolution as measured by the PaO2/FIO2 on the 3rd day and the progressive complications indicated by the onset of MSOF. The length of ICU stay of these patients is related to the number of days on mechanical ventilation.

Serum Cytokine Levels in Human Septic Shock: Relation to Multiple-System Organ Failure and Mortality

Cytokines have been associated with the development of sepsis and diffuse tissue injury following septic or endotoxic challenges in humans. Furthermore, relative organ-system dysfunction, not specific organ dysfunction, appears to predict outcome from critical illness. We hypothesized that persistence of inflammatory cytokines within the circulation, reflecting a generalized systemic inflammatory response, is associated with multiple-system organ failure (MSOF) and death from critical illness. In addition, since hepatic function is central to host-defense homeostasis, we further reasoned that critically ill patients with hepatic cirrhosis would have an increased incidence of MSOF and death following sepsis associated with a persistence of cytokines in the blood. We measured serum levels of tumor necrosis factor (TNF), interleukin (IL) 1, IL-2, IL-6, and interferon gamma (IFG) serially for the first 48 h following the onset of hypotension (systolic blood pressure < 90 mm Hg) thought likely to be due to sepsis in all patients presenting to one ICU. These data were correlated with initial severity of shock and retrospective determination of septic or nonseptic origin, preexistent hepatic cirrhosis, subsequent development of MSOF, and outcome. Fifty-three specific episodes of shock in 52 patients were recorded (35 septic and 18 nonseptic episodes). Mortality was higher in septic patients (41 vs 17 percent, p < 0.01), as was the development of MSOF (29 vs 6 percent, p < 0.001), incidence of cirrhosis (21 vs 0 percent, p < 0.01), and TNF levels over the study interval (p < 0.01). Nonseptic patients also had an initial elevation in TNF over 48-h levels (p < 0.05) that were higher than serum levels reported for normal subjects (chi 2, p < 0.05). There was no relation between peak TNF level and outcome. Sixty-seven percent of the cirrhotic patients had development of MSOF and died, while only 30 percent of the noncirrhotic patients had development of MSOF or died (p < 0.05). The TNF and IL-6 levels in patients who had MSOF or who died were both elevated and did not decrease over time independent of presence or absence of sepsis (p < 0.01). Similarly, IL-6 levels after 12 h were higher in cirrhotic patients than in noncirrhotic septic patients (p < 0.05). No elevation in IL-1, IL-2, or IFG was seen in any patient subpopulation. TNF and IL-6 serum levels are higher in septic than in nonseptic shock, but the persistence of TNF and IL-6 in the serum rather than peak levels of cytokines predicts a poor outcome in patients with shock.

Oxygen Delivery and Consumption and Ventricular Preload Are Greater in Survivors than in Nonsurvivors of the Adult Respiratory Distress Syndrome

In patients with adult respiratory distress syndrome (ARDS), oxygen consumption (VO2) is pathologically dependent on oxygen delivery (DO2). Because of alterations in ventricular function, DO2 may be inadequate to satisfy oxygen demand and may contribute to multiple-system organ failure (MSOF). To determine whether there are differences in DO2, VO2, ventricular function, and MSOF, between survivors and nonsurvivors of ARDS, we studied 29 patients without cardiac disease early in the course of ARDS (hypoxemia, diffuse bilateral pulmonary infiltrates, and pulmonary artery occlusion pressure less than 18 mm Hg). Simultaneous hemodynamic, radionuclide cineangiographic, and oxygen transport measurements were made within 24 h of onset of ARDS. Thirteen survivors had greater DO2 and VO2 than did 16 nonsurvivors (p = 0.004 and 0.001, respectively). MSOF developed in no survivors and in 63% of nonsurvivors. In four survivors and in six nonsurvivors in whom DO2 was changed acutely, VO2 was dependent on DO2 (p = 0.014). Survivors had greater stroke volume index and right and left ventricular end-diastolic volume indices than did nonsurvivors despite similar right atrial and pulmonary artery occlusion pressures. There were no differences between survivors and nonsurvivors in biventricular ejection fractions. We conclude that survivors of ARDS have greater DO2 and VO2 than do nonsurvivors. Survival may be explained by the strong inverse relation between DO2 and development of MSOF.(ABSTRACT TRUNCATED AT 250 WORDS)

Oxygen Delivery in Patients With Adult Respiratory Distress Syndrome Who Undergo Surgery

Identification of the physiologic determinants of survival in patients with adult respiratory distress syndrome (ARDS) has been largely unsuccessful. We evaluated multiple physiologic variables over the first three reversible phases of ARDS. A stepwise multivariant linear regression analysis was used to identify correctable physiologic correlates with survival. Our goal was improved survival. We found that the oxygen delivery and alveolar-arterial oxygen gradient on the third day after the diagnosis of ARDS were the two most important correctable correlates. Both eventually effected the development of multiple-system organ failure and survival. These data provide clinical evidence that optimization of both the oxygen delivery and alveolar-arterial oxygen gradient after the onset of ARDS may allow resolution of ARDS, prevent additional organ dysfunction, and improve survival.