Organ failure in the ICU: cellular alterations

The physiological and biochemical abnormalities that constitute multiple organ failure represent cellular perturbations that, importantly, need to be reconciled with a lack of significant cell death together with availability but impaired utilization of oxygen. In conjunction with the relatively rapid ability of the organ to recover in surviving patients, a paradigm of metabolic shutdown triggered by a decrease in mitochondrial energy production appears increasingly valid. This review discusses data demonstrating temporal changes in oxygen utilization through the septic process, evidence for mitochondrial derangements, and recovery of mitochondrial function preceding clinical recovery.     

Organ failure in the ICU: cardiac alterations

Cardiac alterations may be defined as changes that lead to abnormal cardiac function. They include decrease in preload, increase in afterload, and depressed cardiac contractility. Cardiac dysfunction differs from cardiac failure: cardiac performance is altered, but this does not necessarily mean that the cardiovascular system is failing. Several tools are available to detect cardiac alterations. Some may continuously assess cardiac performance by mainly or exclusively measuring cardiac output, but no information is given about the mechanisms underlying the cardiac output decrease. Doppler echocardiography allows noncontinuous cardiac monitoring, but it is perfectly adapted to evaluation of cardiac performance. It directly visualizes cardiac contractility and assesses cardiac preload. Only when there is an imbalance between oxygen demand and oxygen transport is correction of cardiac alterations required. But the truth is that no study supports the use of one treatment rather than another. Changes in respiratory settings or in respiratory mechanics induce changes in cardiac function and must then be considered in the strategy.     

Pneumothorax in patients with respiratory failure in ICU

Pneumothorax is not an uncommon occurrence in ICU patients. Barotrauma and iatrogenesis remain the most common causes for pneumothorax in critically ill patients. Patients with underlying lung disease are more prone to develop pneumothorax, especially if they require positive pressure ventilation. A timely diagnosis of pneumothorax is critical as it may evolve into tension physiology. Most occurrences of pneumothoraces are readily diagnosed with a chest X-ray. Tension pneumothorax is a medical emergency, and managed with immediate needle decompression followed by tube thoracostomy. A computed tomography (CT) scan of the chest remains the gold standard for diagnosis; however, getting a CT scan of the chest in a critically ill patient can be challenging. The use of thoracic ultrasound has been emerging and is proven to be superior to chest X-ray in making a diagnosis. The possibility of occult pneumothorax in patients with thoracoabdominal blunt trauma should be kept in mind. Patients with pneumothorax in the ICU should be managed with a tube thoracostomy if they are symptomatic or on mechanical ventilation. The current guidelines recommend a small-bore chest tube as the first line management of pneumothorax. In patients with persistent air leak or whose lungs do not re-expand, a thoracic surgery consultation is recommended. In non-surgical candidates, bronchoscopic interventions or autologous blood patch are other options.     

Immunologic alterations and the pathogenesis of organ failure in the ICU

Rapid and marked alterations of innate and adaptive immunity typify the host response to systemic infection and acute inflammatory states. Immune dysfunction contributes to the development of organ failure in most patients with critical illness. The molecular mechanisms by which microbial pathogens and tissue injury activate myeloid cells and prime cellular and humoral immunity are increasingly understood. An early and effective immune response to microbial invasion is essential to mount an effective antimicrobial response. However, unchecked and nonresolving inflammation can induce diffuse vasodilation, increased capillary permeability, microvascular damage, coagulation activation, and organ dysfunction. Control of the inflammatory response to limit tissue damage, yet retain the antimicrobial responses in critically ill patients with severe infection, has been sought for decades. Anti-inflammatory approaches might be beneficial in some patients but detrimental in others. It is now clear that a state of sepsis-induced immune suppression can follow the immune activation phase of sepsis. In carefully selected patients, a better therapeutic strategy might be to provide immunoadjuvants to reconstitute immune function in intensive care unit (ICU) patients. Proresolving agents are also in development to terminate acute inflammatory reactions without immune suppression. This brief review summarizes the current understanding of the fundamental immune alterations in critical illness that lead to organ failure in critical illness.     

Extubation failure in a large pediatric ICU population

OBJECTIVE: To review a large population of children receiving mechanical ventilation to establish a baseline rate of extubation success and failure and to identify those characteristics that place a patient at greater risk of failing planned extubation. DESIGN: Retrospective chart review. SETTING: University-affiliated children's hospital with a 20-bed pediatric ICU. PATIENTS: All 632 patients receiving mechanical ventilation during the 2-year period from July 1, 1996, to June 30, 1998. METHOD: Patients receiving mechanical ventilation were identified via a computerized database. Charts were reviewed of all patients who were reintubated within 72 h of extubation. MEASUREMENTS AND RESULTS: There were 548 planned extubation events, of which 521 were successful. Twenty-seven patients failed planned extubation at least once; only the first attempt at extubation was included in the analysis. The failure rate of planned extubations was 4.9%. Including only patients who had received mechanical ventilation for > 24 h before extubation, the failure rate was 6.0%. For patients intubated > 48 h, the failure rate was 7.9%. The patients who failed extubation were found to be significantly younger and to have received mechanical ventilation longer than those who succeeded, in both the analysis of all patients receiving mechanical ventilation and the subgroup of those receiving mechanical ventilation > 24 h. When only patients who had received mechanical ventilation for > 48 h were analyzed, the difference in age was no longer significant, but the duration of ventilation before extubation was still significantly longer for those who failed. CONCLUSION: We determined the overall failure rate of planned extubations in a large population of pediatric patients to be 4.9%. Those patients who were younger and had received mechanical ventilation longer were more at risk for extubation failure.     

Gut dysbiosis and heart failure: navigating the universe within

Alternations in gut microbial composition (i.e. loss of microbial diversity or ‘gut dysbiosis’) have been associated with heart failure with reduced ejection fraction (HFrEF). It has also been suggested that increased chronic low‐level inflammation and immune system dysregulation seen in patients with HFrEF could be related to gut dysbiosis and increased intestinal permeability. Hence, the concept of modulating gut microbial composition with the goal of reducing systemic inflammation and controlling HFrEF progression has generated a substantial interest in the scientific community. However, several challenges to the gut dysbiosis theory remain as the exact gut microbial composition in HFrEF patients in these studies is not the same and a common microbiome linked to HFrEF is not yet established. With the advances in culture independent sequencing techniques it has also become evident that the gut microbiome may be much more diverse than previously believed. Further, various ‘omic’ technologies have enabled us to appreciate the potential role of gut microbial metabolites in various physiological processes in the host. Hence, identification of specific gut microbial metabolites may offer an alternative approach at solving this gut microbiome‐HFrEF puzzle. In the current review, we evaluate the concept of gut symbiosis, the potential role of gut dysbiosis in systemic inflammation and HFrEF, and finally highlight the challenges faced by the gut dysbiosis theory in HFrEF and provide a framework for the possible solutions.     

经纤支镜支气管肺泡灌洗术治疗急性呼吸衰竭在重症监护病房的临床应用

目的 探讨经纤维支气管镜支气管肺泡灌洗术治疗急性呼吸衰竭在重症监护病房的临床应用效果.方法 选择胸科术后、颅脑术后、创伤昏迷、慢性阻塞性肺疾病患者共35例,均有明显的气道分泌物排出困难、肺不张、肺部感染伴呼吸衰竭、急性呼吸衰竭的表现,均经常规氧疗、抗感染、解痉、平喘、化痰或机械通气等治疗无效后,在重症监护病房采用床旁纤支镜气管吸引及支气管肺泡灌洗、局部注射药物治疗,并监测心电、血压、呼吸、血氧饱和度变化及进行血气分析.结果 所有病例经治疗后,临床症状改善,血气分析PaO2、SaO2与治疗前相比有明显增高(P<0.05).结论 纤支镜气道吸引、支气管肺泡灌洗、局部注射药物的疗法效果确切,能迅速缓解患者因气道阻塞所致肺不张、呼吸困难,有利于气道管理和肺部感染的控制,明显缩短了患者留住重症监护病房的时间及住院周期,降低了住院费用,值得临床推广.     

Severe respiratory failure requiring ICU admission in bone marrow transplant recipients.

Two groups of bone marrow transplant (BMT) recipients with febrile noncardiogenic respiratory failure requiring intensive care unit (ICU) admission, in the early phase of bone marrow transplantation were compared: those who had proven infectious pneumonia and those in whom bronchoalveolar lavage (BAL) failed to establish a diagnosis. Thirty-eight consecutive neutropenic BMT recipients admitted to an ICU with febrile noncardiogenic respiratory failure were enrolled. All of them underwent a BAL with viral, fungal, bacterial, and histopathological examinations. Lung biopsies were performed in nonsurviving patients in order to compare with BAL results. Haematological, biological, respiratory failure and other organ failure parameters, infectious results, outcome, and lung biopsy results were evaluated. BAL allowed an infectious diagnosis to be established in 16 BMT recipients. No aetiology was proven in 22 patients. Without a significant difference in respiratory failure parameters on ICU admission, noninvasive continuous positive airway pressure ventilation, which was given to 11 patients in each group, was significantly more successful in patients with proven infectious pneumonia (6 of 11 versus 0 of 11 patients) and enabled endotracheal intubation to be avoided in significantly more patients with infectious disease (10 of 16 versus 22 of 22 patients). The evolution of patients without diagnosis was significantly different with more frequent renal failure, hepatic failure, and death (20 of 22 versus 9 of 16 patients). Post mortem biopsies confirmed the absence of micro-organisms, but endothelial damage and fibrosis was found in 14 of the 22 patients. In conclusion, in the early phase of bone marrow transplantation the recipients without proven aetiology of pneumonia have a worse outcome than grafted patients with proven infectious pneumonia.     

Survival of patients with bronchiectasis after the first ICU stay for respiratory failure

STUDY OBJECTIVES: Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied. DESIGN: We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded. MEASUREMENTS AND RESULTS: Forty-eight patients (mean age +/- SD, 63 +/- 11 years; mean simplified acute physiology score [SAPS] II, 32 +/- 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival. CONCLUSIONS: We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.     

Gut inflammation in the spondyloarthropathies

In this paper, the ample experimental, clinical, genetic, histopathologic, and immunologic evidence for an important role of the gut in the pathogenesis of spondylarthropathy (SpA) and for an overlap between SpA and Crohn's disease is reviewed. These data suggest that SpA and Crohn's disease should be scientifically and clinically considered as distinct phenotypes of common immune-mediated inflammatory disease pathways rather than as separate disease entities. Classification, diagnosis, and therapy based on pathophysiologic insights is likely to become superior to an approach based exclusively on signs and symptoms, as evidenced by the recent evolution in treatment of SpA by tumor necrosis factor-a blockade.     

Gut inflammation in the spondyloarthropathies

In this paper, the ample experimental, clinical, genetic, histopathologic, and immunologic evidence for an important role of the gut in the pathogenesis of spondylarthropathy (SpA) and for an overlap between SpA and Crohn’s disease is reviewed. These data suggest that SpA and Crohn’s disease should be scientifically and clinically considered as distinct phenotypes of common immune-mediated inflammatory disease pathways rather than as separate disease entities. Classification, diagnosis, and therapy based on pathophysiologic insights is likely to become superior to an approach based exclusively on signs and symptoms, as evidenced by the recent evolution in treatment of SpA by tumor necrosis factor-α blockade.     

Fever in the ICU

Fever is a common problem in ICU patients. The presence of fever frequently results in the performance of diagnostic tests and procedures that significantly increase medical costs and expose the patient to unnecessary invasive diagnostic procedures and the inappropriate use of antibiotics. ICU patients frequently have multiple infectious and noninfectious causes of fever, necessitating a systematic and comprehensive diagnostic approach. Pneumonia, sinusitis, and blood stream infection are the most common infectious causes of fever. The urinary tract is unimportant in most ICU patients as a primary source of infection. Fever is a basic evolutionary response to infection, is an important host defense mechanism and, in the majority of patients, does not require treatment in itself. This article reviews the common infectious and noninfectious causes of fever in ICU patients and outlines a rational approach to the management of this problem.     

Hyperammonemia in the ICU

Patients experiencing acute elevations of ammonia present to the ICU with encephalopathy, which may progress quickly to cerebral herniation. Patient survival requires immediate treatment of intracerebral hypertension and the reduction of ammonia levels. When hyperammonemia is not thought to be the result of liver failure, treatment for an occult disorder of metabolism must begin prior to the confirmation of an etiology. This article reviews ammonia metabolism, the effects of ammonia on the brain, the causes of hyperammonemia, and the diagnosis of inborn errors of metabolism in adult patients.     

Multisystem organ failure predicts mortality of ICU patients with acute respiratory failure secondary to AIDS-related PCP.

OBJECTIVE: To evaluate the ability of a variety of scoring systems to predict mortality of patients admitted to an intensive care unit (ICU) with acute respiratory failure (ARF) secondary to AIDS-related Pneumocystis carinii pneumonia (PCP). METHODS: All patients with AIDS-related PCP admitted to ICU at St. Paul's Hospital between January 1, 1985 and April 1, 1991 were reviewed. For each case, the following scores were calculated from data obtained within 24 h of ICU admission: acute physiology and chronic health evaluation II (APACHE II); acute lung injury score; AIDS score as described by Justice and Feinstein; and modified multisystem organ failure (MSOF) score. The serum lactate dehydrogenase (LDH) level was also recorded when obtained within 24 h of ICU admission. RESULTS: A total of 52 ICU admissions in 51 patients were studied. Overall mortality was 65 percent. Mortality increased with increasing MSOF (p < 0.05) score and LDH (p < 0.05). Based on receiver operating characteristic (ROC) curves, the MSOF score and the LDH were found to be good predictors of mortality. Multivariate logistic regression showed that the MSOF score was the only independent predictor of mortality (p < 0.05). The AIDS score, APACHE II, and the acute lung injury score were not significantly associated with mortality. Addition of the serum LDH level improved the performance of both the MSOF and AIDS scores, though the AIDS score plus LDH performed no better than the LDH alone. Of all the scores tested, the MSOF plus LDH level was the best (p < 0.005) predictor of mortality. CONCLUSIONS: The modified MSOF score and the serum LDH level are the best predictors of mortality of patients admitted to ICU with ARF secondary to AIDS-related PCP. The performance of the MSOF score was enhanced when the LDH level was added. The AIDS score, APACHE II, and the acute lung injury score were not found to be useful in this group of critically ill patients.