© 2005 American Thoracic Society doi: 10.1164/rccm.2412004
Critical Care in AJRCCM 2004The Children's Hospital; Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Health Sciences Center, Denver, Colorado; Division of Pulmonary Medicine, Department of Medicine, Keio University, Tokyo, Japan; Moffitt Hospital, University of California, San Francisco, California; Service de Réanimation Medicale, Hôpital Henri Mondor, Créteil, France; ELEG Colt Laboratories, MRC Centre for Inflammation Research, University of Edinburgh Medical School, Edinburgh, Scotland, United Kingdom Correspondence and requests for reprints should be addressed to Edward Abraham, M.D., University of Colorado Health Sciences Center, Division of Pulmonary Sciences and Critical Care Medicine, 4200 East 9th Avenue, Box C272, Room 5503, Denver, CO 80262-0001. E-mail: edward.abraham{at}uchsc.edu
Conventional Approaches Although heated humidifiers are considered the most efficient humidification devices for mechanical ventilation, endotracheal tube occlusion caused by dry secretions has been reported with heated-wire humidifiers. To evaluate whether inlet chamber temperature, influenced by ambient air and ventilator output temperatures, may affect humidifier performance, Lellouche and coworkers (1) measured hygrometry with three different humidifiers under several conditions, varying ambient air temperatures (high, 28–30°C, and normal, 22–24°C), ventilators with different gas temperatures, and 2-minute ventilation levels. Clinical measurements were performed to confirm bench measurements. Humidifier performance was strongly correlated with inlet chamber temperature in both the bench (p < 0.0001, r2 = 0.93) and the clinical study. With unfavorable conditions, absolute humidity of inspired gas was much lower than recommended (  20 mg H2O/L). Performance was improved by specific settings or new compensatory algorithms. Hygrometry could be evaluated from condensation on the wall chamber only when ambient air temperature was normal but not with high air temperature. Increase in inlet chamber temperature induced by high ambient temperature markedly reduced the performance of heated-wire humidifiers, leading to a risk of endotracheal tube occlusion. The authors concluded that such systems should be avoided in these conditions unless automatic compensation algorithms are used.
Ventilator-induced Lung Injury Li and coworkers (3) evaluated the mechanisms of ventilator-induced lung injury in a mouse model. High VT ventilation (30 ml/kg) was compared with low VT ventilation (6 ml/kg) for 5 hours. The high VT ventilation induced neutrophil influx into the lung and activation of MIP-2 together with JNK activation. In JNK knockout mice, as well as with pharmacologic inhibition of JNK, the deleterious effects of the large VT were attenuated. Therefore, neutrophils, in part through JNK pathways, caused lung injury in part by this pathway.
Dolinay and colleagues (4) evaluated the hypothesis that a low concentration of inhaled CO could protect the lungs against ventilator-induced lung injury. The results showed that low concentration of inhaled CO reduced TNF- In pigs with surfactant deactivation, Steinberg and coworkers (5) determined whether alveolar instability can mechanically injure the lung independent of inflammatory damage and whether positive end-expiratory pressure (PEEP) can be of benefit. Alveolar instability was calculated using in vivo video microscopy by subtracting the alveolar area at end expiration from that at peak inspiration. Alveolar instability was not associated with a significant increase in neutrophil influx or protease activity but did induce a modest increase in tissue and BAL IL-6 levels. PEEP of 15 cm H2O improved alveolar instability and histologic evidence of lung injury as well as oxygenation and lung mechanics. The authors concluded that alveolar instability causes lung injury without increasing neutrophil recruitment or elevating inflammatory mediators and that PEEP stabilizes the abnormally unstable alveoli, leading to reduced lung damage.
Ventilation with increased pressure or volume (overventilation) as well as LPS challenge activates nuclear translocation of nuclear factor–
Ventilator-induced Diaphragmatic Injury In a critical care perspective, Vassilakopoulos and Petrof (8) reviewed the evidence for ventilator-induced diaphragmatic dysfunction together with a discussion of the cellular changes that occur in the diaphragm in this condition and the known effects of other forms of skeletal muscle disuse. To determine the role of antioxidants in diaphragmatic contractile dysfunction produced by prolonged ventilation, Betters and coworkers (9) placed rats on mechanical ventilation for 12 hours with and without 20 mg/kg of Trolox, 6-hydroxy-2,5,7,8-tetramethylchoroman-2-carboxylic acid). Their mechanical ventilation protocol resulted in a 17% reduction in maximal tetanic force production. Trolox attenuated the loss of maximal force generation as well as the increase in the chymotrypsin-like activity of the 20S proteasome that resulted from mechanical ventilation. The authors concluded that oxidative damage induced by prolonged mechanical ventilation is accompanied by diaphragmatic dysfunction with protein degradation and that Trolox blocks this contractile defect. Prolonged mechanical ventilation results in diaphragmatic atrophy and contractile dysfunction, but its effect on the rate of protein synthesis is not known. To investigate this issue, Shanely and coworkers (10) studied rats receiving mechanical ventilation and measured diaphragmatic protein synthesis in vivo. The fractional rate of protein synthesis was computed as the magnitude of (13C)leucine enrichment in proteins divided by the enrichment of (13C)leucine in the precursor pool. After 6 hours of mechanical ventilation, the decrease in diaphragmatic protein synthesis reached 30% for mixed muscle protein and 65% for myosin heavy-chain protein. These decreases persisted for 18 hours. Real-time polymerase chain reaction analyses showed unchanged diaphragmatic levels of type I and IIx myosin heavy-chain mRNA levels during mechanical ventilation. The authors concluded that mechanical ventilation decreases the rate of protein synthesis in the diaphragm by impairment of post-transcriptional events.
Weaning
Animal Models Hypercapnic acidosis has been previously reported to reduce acute lung injury in a model of in vivo ischemia-reperfusion and ventilation-induced lung injury. Laffey and coworkers (12) reported that institution of hypercapnic acidosis with 5% CO2 given before endotoxin-induced lung injury in rats reduced lung injury. There was less severe arterial hypoxemia, improved lung compliance, and reduced alveolar neutrophil infiltration. The hypercapnic acidosis was also associated with an attenuated increase in the higher oxides of nitrogen nitrosothiols in the lung tissue and epithelial lining fluid. Several limitations, as pointed out by the authors, need to be emphasized. Hypercapnia is ineffective when buffered to normal pH, and the studies were done in endotoxin-, not bacterial-induced, lung injury. In addition, the potential efficacy and safety of hypercapnic acidosis when used over longer time periods, particularly in a clinical setting, is unknown. Also, there were no dose-dependent data provided in this study. To investigate the impact of increased intraabdominal pressure on respiration and hemodynamics, Quintel and coworkers (13) measured mean pulmonary artery pressure and the pressure–volume curves of the total respiratory system, lung, and chest wall with or without pneumoperitonium in pigs. Using computed tomography, they found that the amount of edema increased by 30 ± 24% (455 ± 80 g) in the oleic acid–injured lung without pneumoperitonium, whereas the increase was 103 ± 37% (905 ± 134 g) in the presence of pneumoperitonium. The authors concluded that increased intraabdominal pressure exacerbates the amount of edema in oleic acid–induced lung injury.
Physiologic and Radiologic Studies Albaiceta and colleagues (15) used a tomographic method (computed tomography scan) to measure lung aeration (increase in normally aerated lung) and recruitment (decrease in nonaerated lung) in 12 patients with early acute lung injury in whom a pressure–volume curve was used to identify the inflection point on the pressure–volume curve. Aeration at the inflection point was similar in lung injury from pulmonary or extrapulmonary origin. There were no significant changes in the hyperinflated lung tissue. The results support the use of the deflation limb of the pressure–volume curve for adjusting PEEP in patients with acute lung injury. However, there is no direct evidence in this study that adjusting the level of PEEP in this way will improve clinical outcomes.
Cellular and Molecular Mechanisms Sphingosine 1-phosphate produces endothelial cell barrier enhancement in several experimental models. Peng and colleagues (17) reported that sphingosine 1-phosphate infusion produced a rapid reduction in lung weight (> 50%) in isolated, perfused mouse lungs. Also, sphingosine 1-phosphate reduced endotoxin-induced lung vascular permeability and inflammation at both 6 and 24 hours. There was also a reduced extravasation of albumin and myeloperoxidase in renal tissues of the sphingosine 1-phosphate–treated mice that had been given endotoxin. Thus, sphingosine 1-phosphate is a promising new candidate for decreasing pulmonary and renal vascular endothelial permeability and inflammation in clinically relevant causes of lung injury and organ failure. To investigate the effect of triglyceride administration on the function of the respiratory system in ARDS, Lekka and coworkers (18) measured PaO2/FIO2 ratio, compliance of respiratory system, and pulmonary vascular resistance. They observed that the deterioration of lung function and hemodynamics was accompanied by increases in BAL levels of total protein, phospholipids, phospholipase activities, platelet-activating factors, and neutrophils. A high percentage of BAL cells, mainly macrophages, contained lipid droplets in patients with ARDS after lipid administration. The authors concluded that lipids activate neutrophils and macrophages in the intracapillary or alveolar space, leading to their release of inflammatory mediators.
To examine the mechanisms by which To determine the role of plasma levels of von Willebrand factor in clinical outcome from acute lung injury, Ware and coworkers (20) measured plasma von Willebrand factor levels in 559 patients enrolled in National Institutes of Health ARDS Network studies. Baseline von Willebrand factor levels were similar in patients with and without sepsis, and were significantly higher in nonsurvivors (435 ± 333%) versus survivors (306 ± 209%), even when controlling for severity of illness and the presence of sepsis. Higher von Willebrand factor levels were also associated with fewer organ failure–free days. Ventilator strategy had no effect on von Willebrand factor levels. The authors concluded that the degree of endothelial activation and injury is strongly associated with outcome in acute lung injury/ARDS, regardless of the presence or absence of sepsis, and is not modulated by a protective ventilatory strategy. To investigate the ability of sphingosine 1-phosphate, a biologically active lipid generated by hydrolysis of membrane lipids, to prevent regional pulmonary edema accumulation, McVerry and coworkers (21) studied mice receiving high VT (17 ml/kg) ventilation-induced lung injury and beagles receiving high VT ventilation with or without intrabronchial LPS (2 mg/kg) instillation. Intravenously delivered sphingosine 1-phosphate significantly reduced shunt formation, BAL protein, and the accumulation of extravascular lung water induced by endotoxin challenge. Axial and vertical density profiles obtained by computed tomographic imaging showed that sphingosine 1-phosphate improved aeration and edema formation in transitional zones between aerated and consolidated lung regions. The authors concluded that sphingosine 1-phosphate represents a novel therapeutic intervention for the prevention of pulmonary edema through decreasing endothelial permeability. Abe and coworkers (22) generated parabiotic mice by joining green fluorescent protein transgenic mice and wild-type littermates. They investigated if stem/progenitor cells in blood contributed to the regeneration of lung after injury. Wild-type mice received lethal irradiation or intratracheal elastase administration or both. Radiation or the combination of radiation with elastase significantly increased the proportion of bright green cells in the lungs of wild-type mice. By immunostaining, interstitial monocytes/macrophages, subepithelial fibroblast-like interstitial cells and type I alveolar epithelial cells were positive for green fluorescent protein. Approximately 5 to 20% of lung fibroblasts in primary cultures from injured wild-type mice were green fluorescent protein–expressing cells, indicating their origin in blood. The authors concluded that stem/progenitor cells in blood contribute to the repair of radiation-induced lung injury.
Asada and coworkers (23) investigated the expression of peroxisome proliferator–activated receptor
Fluid Biology
Cysteinyl leukotrienes are increased in both animal models and in humans with acute lung injury. Sloniewsky and coworkers (25) assessed the effect of leukotriene D4 (LTD4) on the function of Na,K-ATPase in alveolar epithelial cells and on alveolar fluid clearance in rat lungs. LTD4 (1 x 10–7 M) increased Na, K-ATPase activity at 1 and 5 minutes by 14 (p < 0.05) and 31% (p < 0.001), respectively, in A549 alveolar epithelial cells, accompanied by recruitment of NA,K-ATPase-
Dopamine has been shown to increase active Na+ transport in rat lungs by upregulating alveolar epithelial Na,K-ATPase. Adir and colleagues (26) demonstrated for the first time that alveolar type II cells express the enzyme aromatic-L-amino acid decarboxylase and when treated with the dopamine precursor 3-hydroxy-L-tyrosine (L-dopa) can be made to produce dopamine. Feeding rats a 4% tyrosine diet, which is a precursor of L-dopa and dopamine, produced an increase in urinary dopamine levels, which could be blocked by benserazide, an inhibitor of aromatic-L-amino acid decarboxylase. Furthermore, rats fed tyrosine diet showed an increase in lung alveolar fluid clearance (45% at 48 hours) compared with control animals. Dopaminergic D1 receptor antagonists, but not D2 receptor antagonists, inhibited tyrosine diet–mediated clearance. After feeding with tyrosine diet, cells isolated from rat lungs showed increased protein abundance of Na,K-ATPase-
Epidemiology and Genetics Looking for insights into the molecular alterations of sepsis, Yu and colleagues (27) performed a genomewide gene expression analysis of total mRNA from septic mice. Total mRNA was extracted from the livers of 6 uninfected control mice and 60 septic mice after infusion of either live Escherichia coli or Staphylococcus aureus. Using a murine cDNA microarray system, changes in gene expression were monitored at six time points (uninfected, and 2, 8, 24, 48, and 72 hours). Overall, 4.8% of 6,144 assessed genes were differentially regulated with a greater than twofold change across all time points. Most of the genes with altered expression were commonly present in gram-negative and gram-positive sepsis, but the expression levels of 17 genes were different between both types of sepsis at particular time points after infection. The authors concluded that the results support the hypothesis that both gram-positive and gram-negative sepsis share a final common pathway involved in the pathogenesis of sepsis, but certain genes are differentially expressed under distinct regulation.
Mechanisms in Patients and Volunteers
Endotoxemia in Animals
To determine the role of endogenous IL-6 in endotoxin-induced liver injury, Sewnath and coworkers (30) induced extrahepatic cholestasis by bile duct ligation in IL-6+/+ and IL-6–/– mice. Hepatic pathology did not show any differences 2 weeks after biliary obstruction, but endotoxin challenge (4 µg/kg intraperitoneally) increased mortality (81%) and liver injury in IL-6–/– mice compared with IL-6+/+ mice (44%). Plasma cytokine levels, including IL-1
Sepsis in Animals Lysozyme M is a proteolytic enzyme found in macrophages that hydrolyses the bacterial cell wall and plays an important role in nonimmune host defense against infection. Markart and coworkers (32) used a transgenic mouse model of Klebsiella pneumoniae lung infection, and compared bacterial killing at 24 hours in wild-type mice, deficient mice (M–/M–), and transgenic mice (Mtg) having enhanced expression of lysozyme M. Bacterial killing in Mtg was 9-fold higher than in wild-type mice, and 43-fold higher than in (M–/M–) mice. None of the latter mice survived beyond 72 hours, whereas 25% of wild-type mice and 75% of Mtg mice survived to 120 hours. The study provides further evidence of the importance of lysozyme in nonimmune defenses against bacterial lung infection.
Treatment of Sepsis
In analyzing a retrospective cohort of 97 patients with methicillin-susceptible and 74 patients with methicillin-resistant S. aureus ventilator-associated pneumonia, Combes and coworkers (34), using multivariate analysis, found that the methicillin-resistant patients were older, had higher disease severity scores, and had been mechanically ventilated longer at the onset of the ventilator-associated pneumonia. After controlling for physiologic status and heterogeneity between the groups, methicillin resistance did not significantly affect 28-day mortality of patients with S. aureus ventilator-associated pneumonia who received appropriate antibiotics.
Current guidelines recommend obtaining two separate blood cultures in hospitalized patients with CAP, but the cost-effectiveness of this practice has been questioned. In a cohort of 13,043 Medicare patients having a discharge diagnosis of CAP, Metersky and colleagues (35) assessed factors associated with bacteremia to develop a decision-support tool. In this cohort, bacteremia occurred in 7% of patients. Prior antibiotics were negatively associated with bacteremia, whereas chronic liver disease (OR: 2.3), systolic blood pressure less than 90 mm Hg (OR: 1.7), temperature less than 35 or 40°C or greater (OR: 1.9), heart rate of 125 (OR: 1.9), BUN greater than 30 mg/dl (OR: 2.0), serum sodium less than 130 mmol/L (OR: 1.6), and white blood cell count of less than 5,000 or more than 20,000 (OR: 1.7) independently increased the probability of bacteremia; comparable results were obtained in another validation cohort (n = 12,771). In patients with prior antibiotics and none of the previously described predictive factors, the probability of bacteremia was low (2–3%); the presence of one factor or absence of prior antibiotics increased the risk to 5%, and two or more factors were associated with a higher risk of bacteremia (9–16%). Patients in the high-risk pneumonia score index classes (classes IV and V) were not significantly more likely to have bacteremia. Using this prediction rule to target patients in whom blood cultures are most likely to yield a pathogen would thus result in 38% fewer blood cultures being performed, whereas 89% of patients with bacteremia would still be identified. To evaluate the impact of CAP on medium-term survival of patients, Waterer and coworkers (36) examined a cohort of 404 patients, 378 (93.6%) of whom survived to hospital discharge. Follow-up was available for 366 patients for a mean of 1,058 days; 125 (34.1%) died during follow-up. Independent predictors of late mortality were increased age, comorbid cerebrovascular and cardiovascular disease, altered mental state, a hematocrit of less than 35%, and increasing blood glucose level on admission. Comparison of observed versus expected mortality for an age-, sex-, and race-matched U.S. population showed higher rates in all age groups for patients with CAP; however, in the subgroup of patients with no comorbidity, the observed and expected mortality stratified by age class did not differ significantly. Therefore, an episode of CAP in otherwise healthy adults does not seem to be associated with prolonged adverse outcomes. The prognostic significance of an altered mental status and hematocrit of less than 35% needs to be further elucidated.
SEVERE ACUTE RESPIRATORY SYNDROME Clinical diagnosis of SARS requires the presence of unremitting fever and progressive pneumonia despite antibiotic therapy, particularly in the presence of lymphopenia and raised transaminase levels. Lam and colleagues (38) reported on the case of a female patient who had undergone a successful allogeneic bone marrow transplant for acute myeloid leukemia. The patient presented with fever and a normal chest radiograph. The fever was resolved, but there was a progressive radiologic deterioration and increasing serum antibody titer against SARS coronavirus. She was treated with oral prednisolone and ribavirin, which rapidly normalized her lymphopenia and altered transaminases, chest radiograph, and high-resolution computed tomography appearances. The authors' experience should alert other clinicians in recognizing this atypical indolent presentation of SARS.
Meersseman and coworkers (39) retrospectively analyzed data of inpatients with microbiological or histopathologic evidence of Aspergillus during their ICU stay to determine the impact of invasive aspergillosis (IA) in patients without malignancy in a medical ICU. Using criteria designed for IA in patients with cancer, they identified 127 patients out of 1,850 admissions (6.9%) hospitalized between 2000 and 2003. There were 89 cases (70%) without hematologic malignancy. These patients were classified as proven IA (n = 30), probable IA (n = 37), possible IA (n = 2), or colonization (n = 20). In these patients, mean simplified acute physiology score (SAPS) II score was 52 with a predicted mortality of 48%. The observed mortality was 80% (n = 71). Mortality of proven and probable IA was 97 and 87%, respectively. Postmortem examination was done in 46 of 71 patients, and 27 autopsies (59%) showed hyphael invasion with Aspergillus. Aspergillus infections occurred in five critically ill patients with proven IA who did not have any predisposing factors according to the currently available definitions. Three of these patients had Child C liver cirrhosis. The authors concluded that IA is an emerging and devastating infectious disease in patients in the ICU without malignancy. In those patients, host criteria for probable fungal infections should probably be adapted.
Moloney and coworkers (40) prospectively analyzed data from 45 surgical patients to evaluate the utility of exhaled breath condensate analysis in detecting subclinical acute lung injury caused by cardiac surgery using cardiopulmonary bypass and, to a greater extent, lung resection. The authors compared the analysis of markers of lung injury in exhaled breath condensate and BAL in endotracheally intubated patients before and after coronary artery bypass graft surgery with cardiopulmonary bypass and lobectomy. The neutrophil count and leukotriene B4 concentration in BAL fluid rose after coronary artery bypass graft surgery (p < 0.05), but there was no significant change in leukotriene B4, hydrogen peroxide, or hydrogen ion concentrations in exhaled breath condensate. By contrast, after lobectomy, the concentration in exhaled breath condensate of leukotriene B4, hydrogen peroxide, and hydrogen ions rose significantly (p < 0.05). The authors concluded that exhaled breath condensate is a safe, noninvasive method of sampling the milieu of the distal lung and is sufficiently sensitive to detect markers of inflammation and oxidative stress in patients after lobectomy, but not after the milder insult associated with cardiac surgery. In a heterogeneous population of critically ill patients who were being mechanically ventilated, Victorino and coworkers (41) used a new method, electric impedance tomography, to assess distribution of ventilation into regions or layers that represented one quarter of the lung. As expected, ventilation was gravitationally dependent in all patients. The changes in absolute air content best explained the integral of impedance changes inside the regions of interest. The authors concluded that impedance tomography can reliably assess ventilation distribution during mechanical ventilation.
Improved oxygenation has been shown in patients with acute lung injury when ventilated in prone position. Rimeika and coworkers (42) tested the hypothesis that this was caused by higher regional production of NO in dorsocaudal lung regions. They measured NOS mRNA expression and NO production by citrulline assay in ventral and dorsal lung tissue from patients. In volunteers, regional lung perfusion in prone and supine postures was assessed by single photon emission computed tomography using 99mTc macroaggregated albumin before and after inhibition of NOS by NG-monomethyl-L-arginine infusion. NOS mRNA expression and NO production were significantly higher in dorsal compared with ventral lung regions. In supine posture, lung perfusion was shifted to ventral parts during NOS inhibition, whereas in the prone posture lung perfusion remained unchanged. The authors concluded that the results suggest a role for endogenous NO in regulation of regional pulmonary perfusion.
In view of the prospect of increasing numbers of research protocols, and the problems associated with research involving subjects with decisional impairment, Silverman and colleagues (43) presented in this critical care perspective a multifaceted and complementary approach through which the traditional expertise and domains of the important regulatory and oversight bodies at the federal, state, and institutional levels can ensure that such research is ethically appropriate. To compare the effectiveness of information delivered to family members of critically ill patients by junior and senior physicians, Moreau and coworkers (44) performed a prospective, randomized, multicenter trial in 11 French ICUs. Patients (n = 220) were allocated at random to having their family members receive information by only junior or only senior physicians throughout the ICU stay. There were 92 and 93 evaluable cases in the junior and senior groups, respectively, with no significant differences in baseline characteristics. Between Days 3 and 5, one family representative per patient was evaluated for comprehension of the diagnosis, prognosis, and treatment in the patient; satisfaction with information and care; and presence of symptoms of anxiety and depression. No significant differences were found between the two groups for any of these three criteria. Family members informed by a junior physician were more likely to believe they had not been given enough information time (additional time wanted: 3 [0–6.5] vs. 0 [0–5] minutes, p = 0.01) and to have sought additional explanations from their usual doctor (48.9 vs. 34.4%, p = 0.004). The authors concluded that specialty residents, if given opportunities for acquiring experience, can become proficient in communicating with families and share this task with senior physicians. In this critical care perspective, Miller and Silverman (45) analyzed the ethical relevance of the standard of care in randomized controlled trials with particular attention to the design of critical care trials. To describe longitudinal patterns of critical care use among a nationally representative cohort of elderly patients monitored from the onset of common serious illnesses, Iwashyna (46) retrospectively analyzed data from 1,108,060 fee-for-service Medicare beneficiaries at least 68 years of age and newly diagnosed with serious illnesses: malignancies, stroke, congestive heart failure, hip fracture, or myocardial infarction. Medicare inpatient hospital claims from diagnosis until death (65.1%) or fixed-right censoring (> 4 years) were reviewed. Distinct hospitalizations involving critical care use (ICU or critical care unit) were counted and associated reimbursements were assessed; repeated use was defined as five or more such hospitalizations. Of the cohort, 54.9% used critical care at some time after diagnosis. Older patients were much less likely to ever use critical care (OR 0.31; comparing patients > 90 years old with those aged 68–70 years), even after adjustment. A total of 31,348 patients (2.8%) were repeated users of critical care; they accounted for $3.6 billion in hospital charges and $1.4 billion in Medicare reimbursement. The author concluded that critical care use is common in serious chronic illness and is not associated solely with preterminal hospitalizations. The author added that use is uneven and a minority of patients who repeatedly use critical care account for disproportionate costs. In this thoughtful occassional essay, Misak (47) described a critical care experience from the patient's viewpoint, specifically someone who spent weeks in an ICU with ARDS, severe sepsis, and multiple organ failure.
Cardiac Disorders As part of the Update in Nonpulmonary Critical Care series, McPherson and Manthous (48) reviewed recent advances in the sophistication of pacemakers and cardioverter-defibrillators, which are implanted in patients with cardiovascular disease for an ever-increasing array of indications.
Obesity
Otolaryngology
Conflict of Interest Statement: D.A. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; A.I. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; M.M. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; F.L. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript; W.M. has been reimbursed for travel by GlaxoSmithKline (GSK), Zambon, AstraZeneca (AZ), Boehringer Ingelheim, Pfizer,and Micromet and has received honoraria from GSK, AZ, Zambon, and Pfizer for participating as a speaker at scientific meetings. He serves on Advisory Boards for GSK, Pfizer, Aimirall, Amgen, Bayer, and Micromet and serves as a consultant for Pfizer and SMB Pharmaceuticals. He has received research grants to support work carried out in W.M.'s laboratory from SMB, Pfizer, Ceremedix, GSK, Chugi, and Novartis; E.A. has been a consultant for Eli Lilly in 2002 and 2003 and also received clinical research contracts from Eli Lilly.
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