key: cord-1043184-k82ddapa
authors: Anderson, Michaela R.; Shashaty, Michael G.S.
title: The Impact of Obesity in Critical Illness
date: 2021-08-05
journal: Chest
DOI: 10.1016/j.chest.2021.08.001
sha: 26ec370ca5f44dccd11caab386202e093618bad1
doc_id: 1043184
cord_uid: k82ddapa

The prevalence of obesity is rising worldwide. Adipose tissue exerts anatomic and physiologic effects with significant implications for critical illness. Changes in respiratory mechanics cause expiratory flow limitation, atelectasis, and ventilation/perfusion mismatch with resultant hypoxemia. Altered work of breathing and obesity hypoventilation syndrome may cause hypercapnia. Challenging mask ventilation and peri-intubation hypoxemia may complicate intubation. Patients with obesity are at increased risk of acute respiratory distress syndrome and should receive lung-protective ventilation based on predicted body weight. Increased positive end expiratory pressure (PEEP), coupled with appropriate patient positioning, may overcome the alveolar decruitment and intrinsic PEEP caused by elevated baseline pleural pressure, though evidence is insufficient regarding the impact of high PEEP strategies on outcomes. Venovenous extracorporeal membrane oxygenation may be safely performed in patients with obesity. Fluid management should account for increased prevalence of chronic heart and kidney disease, expanded blood volume, and elevated acute kidney injury risk. Medication pharmacodynamics and pharmacokinetics may be altered by hydrophobic drug distribution to adipose depots and comorbid liver or kidney disease. Obesity is associated with increased risk of venous thromboembolism and infection; appropriate dosing of prophylactic anti-coagulation and early removal of indwelling catheters may decrease these risks. Obesity is associated with improved critical illness survival in some studies. It is unclear whether this reflects a protective effect or limitations inherent to observational research. Obesity is associated with increased risk of intubation and death in SARS-CoV-2 infection. Ongoing molecular studies of adipose tissue may deepen understanding of how obesity impacts critical illness pathophysiology.

One-third of adults in the United States and 13% worldwide meet the World Health Organization (WHO) definition of obesity (body mass index (BMI) ≥30kg/m 2 ). 1,2 A substantial body of literature details the impact of obesity on critical illness pathophysiology and management. [3] [4] [5] In this state-of-the-art concise review, we will highlight clinically relevant and recent studies to equip clinicians with an understanding of obesity's effects on pathophysiology, logistics, and outcomes in the critical care setting.

Obesity may exert physical, metabolic, and molecular effects across multiple organ systems, and is associated with numerous associated comorbidities such as diabetes mellitus, hypertension, chronic kidney disease, hepatic steatosis, and obstructive sleep apnea. 6 This underlying pathophysiologic milieu has both direct and indirect impacts in the setting of critical illness, summarized in Figure 1 . Obesity, however, is a heterogeneous disease. Some effects of obesity may only become relevant for patients with very high BMI (≥40-50 kg/m 2 ). Others may depend on adipose distribution or contribution of lean muscle mass to BMI. Excess visceral adipose tissue is associated with a chronic inflammatory state and insulin resistance. 6, 7 Circulating adipokines such as leptin, resistin, visfatin, and adiponectin have pleiotropic immunomodulatory effects that could impact acute organ dysfunction syndromes, but J o u r n a l P r e -p r o o f adipokine concentrations are not explained solely by BMI. 7 Thus, in the system-based discussion that follows it is of paramount importance to remember that pathophysiologic effects of obesity may vary substantially across the obese population.

Obesity has well-described effects on respiratory anatomy and physiology that may impact baseline and sick-state gas exchange as well as airway and ventilator management. Increased airway resistance from parapharyngeal adipose tissue renders the upper airway susceptible to collapse, as seen in obstructive sleep apnea. 8 Increased baseline pleural pressure from abdominal and chest wall adiposity results in reduced expiratory reserve volume and functional residual capacity. [9] [10] [11] Patients with obesity are thus susceptible to collapse of peripheral dependent airways, atelectasis, and tidal ventilation below the lower inflection point of the inspiratory pressure-volume curve, with a corresponding decrease in lung compliance. 10, 11 Because dependent perfusion is increased in some patients with obesity, concomitant basilar atelectasis may cause ventilation/perfusion (V/Q) mismatch and resultant hypoxemia. 12 Severe obesity may also substantially increase the metabolic demand of breathing: one study showed that approximately half of the 60% increase in resting oxygen consumption among patients with obesity (mean BMI 53 kg/m 2 ) compared with controls was due to respiratory muscle demand. 13 This increased ventilatory load results in a compensatory increase in neural respiratory drive, 14 a mechanism that fails in obesity hypoventilation syndrome (OHS) with consequent decreased neural drive, hypercapnia, and hypoxemia. 15 

Obesity is associated with difficult mask ventilation, including need for twoprovider ventilation or airway adjuncts, likely owing to mask fit challenges, increased upper airway resistance, and reduced respiratory system compliance. 16 Data are less clear as to BMI's specific impact on difficult tracheal intubation. Large operating room (OR) studies suggest small or no risk differences in patients with BMI ≥35-40 kg/m 2 . 17, 18 In a multicenter study of patients intubated in the ICU, however, De Jong et al. showed that obesity was 1.5-2 times more prevalent in those with difficult intubation. 19 Both OR and ICU studies show that modified Mallampati class III or IV, which is associated with obesity, is a more important independent predictor of difficult intubation than BMI. 17, 19 Peri-intubation hypoxemia, already common in ICU patients, is of particular concern in patients with obesity since they have shown more rapid and severe oxygen desaturation during preoperative intubation. 20 OR interventions shown to improve peri-intubation PaO2 in patients with BMI>40 kg/m 2 include 30° reverse Trendelenburg or 25° head up positioning, noninvasive ventilation (NIV) during preoxygenation, and post-intubation recruitment maneuver. 20,21 One randomized trial of patients with BMI >35 kg/m 2 found that high flow nasal cannula (HFNC) alone resulted in lower nadir end-tidal oxygen saturation during the two minutes after preoperative intubation compared with NIV. 22 A recent systematic review highlighted trials in critically ill patients showing that preintubation NIV, potentially with addition of apneic oxygenation with HFNC, may decrease the depth of peri-intubation desaturation. 23 These trials included patients with normal and elevated BMI, and impact of the interventions on patient-centered outcomes remains unclear.

J o u r n a l P r e -p r o o f Acute respiratory distress syndrome ICU patients with obesity have elevated risk of acute respiratory distress syndrome (ARDS), possibly related to baseline V/Q mismatch, atelectrauma from alveolar collapse during tidal ventilation, or even a proinflammatory response from adipose tissue. 7, 24 As with all ARDS patients, patients with high BMI should be ventilated with tidal volumes normalized to ARDSNet protocol predicted body weight based on height and sex. 10, 25 While a plateau pressure (Ppl) goal ≤30 cm H2O remains standard, it is important for clinicians to understand that higher Ppl in patients with obesity may not entirely reflect lung-injurious increased transpulmonary pressureelevated baseline pleural pressure related to adiposity may also contribute to this finding. 11 Several recent studies have explored optimal positive end-expiratory pressure (PEEP) titration for ARDS patients with class III obesity, based on earlier perioperative studies suggesting that higher extrinsic PEEP may improve respiratory system compliance, oxygenation, and expiratory flow limitation. 26, 27 In a series of crossover studies in ARDS patients with mean BMI range 48-57 kg/m 2 , average PEEP of 20-22 cm H2O was found to optimize end-expiratory lung volumes, V/Q matching and oxygenation, lung compliance, and ventilation homogeneity without overdistention, far above the average of 12-13 cm H2O set by clinicians based on the ARDSNet low PEEP table. 25, [28] [29] [30] Hemodynamics were preserved even when recruitment maneuvers were used prior to PEEP titration, and a corresponding experiment in a swine model of obese ARDS found that pulmonary vascular resistance and pressure decreased with this method. 31 Should ARDS patients with obesity be managed with this approach? First it J o u r n a l P r e -p r o o f should be noted that the studies were small (<20 patients each). Second, this approach increased mortality in a broad population of patients with moderate to severe ARDS. 32 Finally, accurate assessment of lung compliance and driving pressure, used to optimize PEEP settings, may be complicated by end-expiratory complete airway closure, present in up to two-thirds of ARDS patients with BMI ≥40 kg/m 2 . 33 At PEEP below airway opening pressure, standard end-expiratory airway pressure measurements may therefore underestimate alveolar pressure and overestimate driving pressure and respiratory system elastance. There is a sound physiologic basis, however, for a higher PEEP approach in patients with very high BMI, and trials testing clinical outcomes using this strategy in the obese population are clearly warranted.

Prone positioning is feasible and, despite slightly conflicting observational data, 34, 35 likely to benefit patients with obesity who develop ARDS and severe hypoxemia. Notably, the average BMI in the PROSEVA randomized clinical trial was 28-29 kg/m 2 . 36 Prone positioning is also known to improve oxygenation and lung compliance of patients with obesity in the perioperative setting. 37 Clinical teams may benefit from additional planning to address logistical challenges involved in turning patients with very high BMI, particularly if needed rapidly in the setting of clinical instability.

Obesity should not be considered an absolute contraindication to venovenous extracorporeal membrane oxygen (VV-ECMO) in patients with severe forms of ARDS.

Historically, the use of VV-ECMO in patients with obesity was discouraged due to concerns regarding technical difficulties with cannulation, obtaining sufficient flow indexed to body surface area, greater comorbidity burden, and challenges with early J o u r n a l P r e -p r o o f mobilization. 38 Multiple observational studies, however, suggest that VV-ECMO in patients with high BMI is safe, feasible, and associated with similar 39 or improved 40 outcomes compared to non-obese patients. VV-ECMO has also been safely employed to transport patients with obesity who have refractory respiratory failure to quaternary care centers. 38 EOLIA, an international multi-center randomized controlled trial of VV-ECMO in severe ARDS, had BMI means of ~28.5 kg/m 2 in both VV-ECMO and control groups (despite excluding patients with BMI ≥45 kg/m 2 ), suggesting that many study subjects were overweight or obese. 41 No sub-group or safety analyses were performed by BMI. When managing patients with obesity receiving VV-ECMO support, additional venous drainage cannulas may be necessary to provide enough extracorporeal blood flow to meet oxygenation needs when cardiac output is high, 38 and close attention should be paid to the circuit for clot formation and cannula site infections. Given the limitations in the existing data, particularly for those with BMI >50 kg/m 2 , providers should consider local expertise in choosing candidates for cannulation.

Obesity also impacts respiratory failure beyond ARDS. Higher BMI is a risk factor for primary graft dysfunction (PGD) after lung transplantation, potentially for reasons similar to the factors noted above that may contribute to ARDS risk. 42 A recent study found that computed tomography-quantified abdominal subcutaneous adipose tissue was associated with PGD. 43 The finding that adipose correlated with circulating levels of the immune modulating adipokine leptin and vascular endothelial markers raises the possibility of a molecular link between adiposity and PGD. Obesity is a sine qua non of OHS, which may progress to acute on chronic hypercapnic respiratory failure in the J o u r n a l P r e -p r o o f ICU. Clinicians must consider current and prior available data on partial pressure of carbon dioxide, serum bicarbonate concentration, and other measures of acid-base status in order to distinguish acute and chronic components. Cohort studies have demonstrated that noninvasive ventilation can be used to treat acute respiratory failure in OHS patients with intubation avoidance rates of 83-94% and adjusted mortality rates comparable to patients with COPD exacerbations. 44 OHS patients may require higher pressures, management in a sitting position, and extended initial noninvasive ventilation to significantly improve blood gas parameters.

A study by O'Brien et al. showed in a risk-adjusted analysis of 508 patients that obese medical ICU patients had shorter time to successful extubation than those with BMI<25 kg/m 2 , with no difference in reintubation rates. 45 These findings remain more convincing than prior studies, which were limited by lack of appropriate adjustment for confounders. Interestingly, obesity was not a typical criterion in studies supporting a recent consensus recommendation for extubation to NIV in high-risk patients. 46 As in the non-obese, patients with obesity who have hypercapnia during spontaneous breathing trials may be good candidates for this approach. HFNC has also been studied in the prevention of respiratory failure after cardiac surgery in patients with obesity, with some data suggesting similar efficacy to NIV while other data suggest no improvement in atelectasis compared with standard nasal cannula. 47 50 Of note, however, the percutaneous approach may not be feasible when anatomic landmarks on the neck are obscured.

Obesity results in multiple cardiovascular changes including increased blood volume, stroke volume, and cardiac output, increased left ventricular (LV) and left atrial (LA) filling pressures, LV hypertrophy and LA enlargement, and increased risk for LV dysfunction. 51, 52 These factors likely increase the risk of atrial fibrillation, as may sleepdisordered breathing, which results in autonomic changes that may be arrhythmogenic. 53, 54 Patients with obstructive sleep apnea or OHS may also develop pulmonary hypertension and right ventricular dysfunction. 55 Intensivists should correspondingly have an increased index of suspicion for these conditions while realizing that many patients with obesity have normal cardiac function.

How to account for higher BMI in fluid resuscitation remains unclear. Although initial fluid regimens for sepsis, for example, are indexed to weight, 56 obesity-related blood volume increases plateau at the upper extremes of BMI. 51 In trauma patients who were largely managed with non-weight-based initial fluid resuscitation, Winfield et al. showed that metabolic acidosis was slower to resolve in patients with BMI ≥40 kg/m 2 than in those with normal BMI, raising the possibility that such an approach might under-resuscitate patients with obesity. 57 Acknowledging the limitations of current evidence and potential risks of excess fluid administration, a weight-based approach to J o u r n a l P r e -p r o o f resuscitation, with modification at very high BMI and heightened attention to both perfusion goals and early signs of fluid overload, may be most prudent.

Obesity is a risk factor for chronic kidney disease (CKD) and acute kidney injury (AKI) in critical illness populations. 58, 59 Mechanisms proposed for the obesity-AKI link include subclinical CKD, intraabdominal hypertension, and alteration in baseline and evoked circulating inflammatory mediators and adipokines. 59 A recent study in critically ill trauma patients found that the association of BMI with AKI risk was in part explained by creatine kinase levels, raising the possibility that higher BMI could predispose patients to rhabdomyolysis-mediated kidney injury. 60 This finding may be specific to trauma patients, given the frequency of rhabdomyolysis and a demographic including young, healthy individuals whose high BMI may sometimes reflect increased muscle mass rather than adiposity.

Consensus criteria define AKI in part by urine output in ml/kg/h. 61 This may bias classification in favor of AKI particularly in patients with very high weight, though there is currently no consensus to index urine output to adjusted or ideal weight estimates such as those using height and sex. 62 Creatinine criteria for AKI are less susceptible to this bias, and novel AKI biomarkers more specific to kidney injury may ultimately supplant 

Obesity is associated with increased risk of venous thromboembolism (VTE) in both the general population and hospitalized patients. 66 This may be due to increased circulating pro-coagulant factors, 67 slowed venous return related to increased intraabdominal pressure, 68 or inadequate dosing of prophylactic anti-coagulation. 69 Diagnosis of VTE on ultrasound in obesity may be challenging as increased subcutaneous tissue can make visualizing deeper proximal veins difficult. 70 Establishing venous compressibility with significant subcutaneous tissue may be difficult, potentially resulting in false positive results. 70 Clinicians should incorporate a careful physical exam and clinical impression into the interpretation of ultrasound results in critically ill patients with obesity and suspected VTE.

Whether obesity contributes to excess pressure ulcers in hospitalized patients remains unclear. 71 Studies are limited by failure to account for differences in nursing care intensity for patients with high BMI, and often do not distinguish pressure ulcer sites and stages. Pressure ulcer mechanisms specific to patients with obesity include J o u r n a l P r e -p r o o f increased difficulty re-positioning, increased tensile pressure on skin, greater sweat production within more skin folds, and impaired micro-circulation. At this time, standard care is recommended for pressure ulcer prevention including regular repositioning and frequent checks for early pressure injury.

Bariatric hospital beds are typically at least 50 inches wide, have greater weight capacity, and may help with positioning and mobility in patients with a BMI >40 kg/m 2 . 72 Increased bed width allows caregivers to roll patients to both sides without pushing or lifting. Further, patients with obesity who want to reposition themselves in narrow hospital beds must use abdominal muscles to sit up while wider beds allow them to roll over and push to a seated position allowing greater movement and independence.

Obesity may be a risk factor for bloodstream infections, pneumonia, and soft tissue infections in hospitalized and critically ill patients. 73, 74 Potential contributors include altered cellular immunity, 75 Incorrect blood pressure cuff size may affect accuracy of blood pressure measurement and lead to inappropriate care in the ICU. Physicians should confirm that the appropriate cuff is being used in patients with obesity.

The placement of central venous catheters may be more challenging in the presence of increased subcutaneous adipose tissue. Ultrasound guidance should mitigate the increased challenges in identifying and cannulating vessels, though dilation and catheter placement through greater subcutaneous tissue, particularly with a femoral approach, may still be more challenging. Central venous catheters may be more prone to infection in patients with more skin folds, a large pannus, and greater local sweat production. As in all patients, central venous catheters should only be used when necessary, assessed frequently, and removed for any signs of infection.

Increased soft tissue density and upward displacement of the diaphragm may make interpretation of x-rays in patients with obesity more challenging. CT scans in such patients may exhibit increased noise due to radiation scatter caused by subcutaneous adipose tissue. This is particularly problematic when a larger field-of-view is required as in abdominal and pelvic imaging. Increased radiation dose may mitigate some of these effects. 77 Bedside ultrasound may provide additional diagnostic information though quality may be limited as greater adipose tissue leads to decreased penetration of sound waves, difficulty identifying landmarks due to beam attenuation, J o u r n a l P r e -p r o o f and difficulty adequately positioning patients. Whether this alters diagnostic accuracy of lung ultrasound in particular has not been reported.

Many physicians believe that patients with obesity have worse ICU survival than those without. However, the preponderance of data suggests that this is unlikely.

Recent meta-analyses 78, 79 have largely overcome the significant statistical heterogeneity limiting earlier studies. The majority of recent studies, including an analysis of >50,000 patients at 139 U.S. hospitals, 80 demonstrate that obesity is associated with similar or decreased mortality in mixed ICU populations, 81 sepsis, 79 and ARDS. 82 In-depth comparisons of these studies can be found in recent systematic reviews. 78, 79 There are multiple potential explanations for this "obesity paradox." Obesity may have protective physiologic effects that contribute to improved ICU outcomes (see Research/Emerging Literature). Additionally, differences in fluid management, vasopressor dosing, and other aspects of treatment may differ systematically between critically ill patients with and without obesity, potentially impacting survival. It is also possible, however, that the obesity paradox reflects limitations inherent in observational studies of critical illness. Pre-existing beliefs that patients with obesity are more ill or in need of closer monitoring than non-obese patients with comparable derangements may favor ICU admission of less ill patients with obesity, on average, leading to "collider bias," in which one of the study selection variables (ICU admission) is linked to both the J o u r n a l P r e -p r o o f predictor (BMI) and outcome (survival). 83 Furthermore, residual confounding may persist in all retrospective analyses, particularly those from large databases. Reviews of the obesity paradox in critical illness are available for additional details on this topic. 78, 84 Research/Emerging Literature Whether changes in adipose tissue influence survival from critical illness remains unclear. Serum from critically ill patients, regardless of body mass, stimulates proliferation and accumulation of small adipocytes. 85 These new adipocytes lead to the accumulation of anti-inflammatory macrophages 86 which facilitate lipid storage while improving insulin sensitivity, 86 and protecting mitochondrial function. 87, 88 Adipose tissue may also serve as an energy reservoir in critical illness. In both mice and humans, obesity was associated with less muscle mass and function loss during critical illness due to greater mobilization of triglycerides from adipose tissue and less utilization of ectopically stored lipids and proteins. 89, 90 Further work is needed to identify how early in the course of critical illness these adipose tissue changes occur and whether they influence survival.

Adipokines regulate multiple immune cells and inflammatory pathways, but associations with organ dysfunction and survival are inconsistent. Circulating leptin has been associated with higher, similar, and lower survival in critical illness. [91] [92] [93] Higher adiponectin levels were associated with higher mortality in sepsis and ARDS from extrapulmonary causes, 94,95 but with lower Sequential Organ Function Assessment score on ICU admission. 96 Resistin and visfatin concentrations have demonstrated more J o u r n a l P r e -p r o o f consistent associations with decreased survival in critical illness. 97, 98 Reviews of adipokines and adipose tissue in critical illness are recommended for in-depth summaries. 7, 98, 99 

Obesity is associated with an increased risk of testing positive, 100 developing severe disease, 101 and dying 102 from SARS-CoV-2 infection after adjustment for age, sex, and comorbidities. These associations may be modified by age with a stronger association between obesity and respiratory failure, ICU admission, or death among patients <60-65 years old. 101, 102 Obesity has been associated with similar or decreased risk of death in critical illness (see Obesity and outcomes), which differs from findings in COVID-19. 101, 102 These disparate findings may reflect the study of a single homogeneous disease, differences in the allocation of pandemic-limited resources such as ventilators, prone positioning, and ECMO, or pathophysiologic mechanisms specific to SARS-CoV-2 infection. For example, the gene for the SARS-CoV-2-binding ACE2 receptor is upregulated in adipose tissue, 103 suggesting that adipose may serve as a reservoir for the SARS-CoV-2 virus, though evidence for this is currently lacking. 104

J o u r n a l P r e -p r o o f Obesity remains a common but unique challenge in critical illness. Recent studies have extended understanding of obesity-related pulmonary pathophysiology from the perioperative to the ICU setting. Obesity's impact on multiple organ systems, medication dosing, and ICU complications and logistics are essential for clinicians to consider in management decisions ( Table 1) 

Prevalence of obesity and trends in the distribution of body mass index among US adults

Pathophysiology and Management of Acute Respiratory Distress Syndrome in Obese Patients

Obesity in the critically ill: a narrative review

Endocrine, metabolic, and morphologic alterations of adipose tissue during critical illness

Obstructive sleep apnea syndrome in morbid obesity: Effects of intragastric balloon

Total Respiratory System, Lung, and Chest Wall Mechanics in Sedated-Paralyzed Postoperative Morbidly Obese Patients

The effects of body mass index on lung volumes

Respiratory restriction and elevated pleural and esophageal pressures in morbid obesity

Respiratory system mechanics in sedated, paralyzed, morbidly obese patients

The impact of morbid obesity on oxygen cost of breathing (VȮ(2RESP)) at rest. American Journal of Respiratory and Critical Care Medicine

Neural respiratory drive in obesity

Diaphragm activity in obesity

Incidence and predictors of difficult and impossible mask ventilation

High body mass index is a weak predictor for difficult and failed tracheal intubation: A cohort study of 91,332 consecutive patients scheduled for direct laryngoscopy registered in the danish anesthesia database

The influence of morbid obesity on difficult intubation and difficult mask ventilation

Early Identification of Patients at Risk for Difficult Intubation in the Intensive Care Unit

Preoxygenation is more effective in the 25° head-up position than in the supine position in severely obese patients: A randomized controlled study

Noninvasive ventilation and alveolar recruitment maneuver improve respiratory function during and after intubation of morbidly obese patients: A randomized controlled study

High-flow Nasal Cannulae Versus Non-invasive Ventilation for Preoxygenation of Obese Patients: The PREOPTIPOP Randomized Trial

Tracheal intubation in critically ill patients: a comprehensive systematic review of randomized trials

Ventilation with lower tidal volumes as compared with traditional tidal volumes for acute lung injury and the acute respiratory distress syndrome

Positive end-expiratory pressure improves respiratory function in obese but not in normal subjects during anesthesia and paralysis

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients

Recruitment Maneuvers and Positive End-Expiratory Pressure Titration in Morbidly Obese ICU Patients

Transpulmonary Pressure Describes Lung Morphology During Decremental Positive End-Expiratory Pressure Trials in Obesity

Lung Recruitment in Obese Patients with Acute Respiratory Distress Syndrome

High Pleural Pressure Prevents Alveolar Overdistension and Hemodynamic Collapse in ARDS with Class III Obesity

Writing Group for the Alveolar Recruitment for Acute Respiratory Distress Syndrome Trial I. Effect of lung recruitment and titrated positive end-expiratory pressure (peep) vs low peep on mortality in patients with acute respiratory distress syndrome: A randomized clinical trial

Prevalence of Complete Airway Closure According to Body Mass Index in Acute Respiratory Distress Syndrome: Pooled Cohort Analysis

Feasibility and effectiveness of prone position in morbidly obese patients with ARDS: A case-control clinical study

Abdominal obesity and prolonged prone positioning increase risk of developing sclerosing cholangitis in critically ill patients with influenza Aassociated ARDS

Prone positioning in severe acute respiratory distress syndrome

Prone positioning improves pulmonary function in obese patients during general anesthesia

Morbid obesity is not a contraindication to transport on extracorporeal support

Effect of body mass index on the outcome of surgical patients receiving extracorporeal devices (VV ECMO, pECLA) for respiratory failure

Does Weight Matter? Outcomes in Adult Patients on Venovenous Extracorporeal Membrane Oxygenation When Stratified by Obesity Class

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome

Obesity and primary graft dysfunction after lung transplantation: the Lung Transplant Outcomes Group Obesity Study

Adipose tissue quantification and primary graft dysfunction after lung transplantation: The Lung Transplant Body Composition study

Noninvasive ventilation in acute hypercapnic respiratory failure caused by obesity hypoventilation syndrome and chronic obstructive pulmonary disease

The association between body mass index, processes of care, and outcomes from mechanical ventilation: A prospective cohort study

Clinical Practice Guideline: Inspiratory Pressure Augmentation During Spontaneous Breathing Trials,&#xa0;Protocols Minimizing Sedation, and Noninvasive Ventilation Immediately After Extubation

High-Flow Nasal Cannula Therapy Versus Intermittent Noninvasive Ventilation in Obese Subjects After Cardiothoracic Surgery

Direct extubation onto high-flow nasal cannulae post-cardiac surgery versus standard treatment in patients with a BMI ≥30: a randomised controlled trial

A comparative study of the complications of surgical tracheostomy in morbidly obese critically ill patients

Safety of bedside percutaneous tracheostomy in the critically ill: Evaluation of more than 3,000 procedures

Estimating blood volume in obese and morbidly obese patients

Obesity and the risk of heart failure

Obesity and Atrial Fibrillation: Epidemiology, Pathophysiology and Novel Therapeutic Opportunities

Obesity and the risk of new-onset atrial fibrillation

Obesity and right ventricular structure and function: The MESA-right ventricle study

Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock

Traditional resuscitative practices fail to resolve metabolic acidosis in morbidly obese patients after severe blunt trauma

Obesity and risk for chronic renal failure

Body mass index and acute kidney injury in the acute respiratory distress syndrome

Relationship of body mass index, serum creatine kinase, and acute kidney injury after severe trauma. The journal of trauma and acute care surgery

Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury

Drug Dosing in the Critically Ill Obese Patient. Critical Care Management of the Obese Patient2012

A new equation to estimate glomerular filtration rate

Anesthesia in the obese patient: pharmacokinetic considerations

Drug dosing in the critically ill obese patient-a focus on sedation, analgesia, and delirium

Epidemiology of venous thromboembolism in the Framingham Heart Study

Association between obesity and a prothrombotic state: the Framingham Offspring Study

Impact of obesity on venous hemodynamics of the lower limbs

Enoxaparin Dosing at Extremes of Weight: Literature Review and Dosing Recommendations

Imaging of suspected pulmonary embolism and deep venous thrombosis in obese patients

Body mass index and pressure ulcers: improved predictability of pressure ulcers in intensive care patients

What Bed Size Does a Patient Need? The Relationship Between Body Mass Index and Space Required to Turn in Bed

Obesity and site-specific nosocomial infection risk in the intensive care unit

Impact of obesity in the critically ill trauma patient: a prospective study

Obesity Impairs the Adaptive Immune Response to Influenza Virus

Underdosing of common antibiotics for obese patients in the ED

European obesity and the radiology department. What can we do to help?

Is body mass index associated with outcomes of mechanically ventilated adult patients in intensive critical units? A systematic review and meta-analysis

Increased body mass index and adjusted mortality in ICU patients with sepsis or septic shock: a systematic review and metaanalysis

Does Obesity Protect Against Death in Sepsis? A Retrospective Cohort Study of 55,038 Adult Patients

The paradox prevails: Outcomes are better in critically ill obese patients regardless of the comorbidity burden

Can body mass index predict clinical outcomes for patients with acute lung injury/acute respiratory distress syndrome? A meta-analysis

The obesity paradox in critically ill patients: a causal learning approach to a casual finding

Is There an Obesity Paradox in Critical Illness? Epidemiologic and Metabolic Considerations

Proliferation and differentiation of adipose tissue in prolonged lean and obese critically ill patients

Critical illness induces alternative activation of M2 macrophages in adipose tissue

Tissue-specific glucose toxicity induces mitochondrial damage in a burn injury model of critical illness

Van den Berghe G. FGF21 Response to Critical Illness: Effect of Blood Glucose Control and Relation With Cellular Stress and Survival

Premorbid obesity, but not nutrition, prevents critical illness-induced muscle wasting and weakness

Adipose tissue protects against sepsis-induced muscle weakness in mice: from lipolysis to ketones

Plasma leptin levels are increased in survivors of acute sepsis: Associated loss of diurnal rhythm in cortisol and leptin secretion

Relevance of serum leptin and leptin-receptor concentrations in critically ill patients

A leptin serum concentration less than 10 ng/ml is a predictive marker of outcome in patients with moderate to severe secondary peritonitis. European surgical research. Europaische chirurgische Forschung

Serum adiponectin upon admission to the intensive care unit may predict mortality in critically ill patients

Plasma Adiponectin, clinical factors, and patient outcomes during the acute respiratory distress syndrome

Sepsis induced changes of adipokines and cytokines -Septic patients compared to morbidly obese patients

Clinical role of serum pre-B cell colony-enhancing factor in ventilated patients with sepsis and acute respiratory distress syndrome. Scandinavian journal of infectious diseases

Association between adipokines and critical illness outcomes. The journal of trauma and acute care surgery

The Role of Adipose Tissue and Adipokines in Sepsis: Inflammatory and Metabolic Considerations, and the Obesity Paradox

Risk factors for SARS-CoV-2 among patients in the Oxford Royal College of General Practitioners Research and Surveillance Centre primary care network: a cross-sectional study

Body Mass Index and Risk for Intubation or Death in SARS-CoV-2 Infection: A Retrospective Cohort Study

Obesity and Mortality Among Patients Diagnosed With COVID-19: Results From an Integrated Health Care Organization

Association of high level gene expression of ACE2 in adipose tissue with mortality of COVID-19 infection in obese patients

Abdominal Surgery in Patients with COVID-19: Detection of SARS-CoV-2 in Abdominal and Adipose Tissues

HOB: head-of-bed. PEEP: positive endexpiratory pressure. VV-ECMO: venovenous extracorporeal membrane oxygenation. NIV: non-invasive ventilation. LV: left ventricle. RV: right ventricle

J o u r n a l P r e -p r o o f