Survival of the ‘Fattest’ – Paradox not paradigm! #FOAMed #FOAMcc

By: Dr Richard Pertwee (Clinical ICU Fellow)

Edited by: Dr Jonny Wilkinson


The obvious pun comes…Obesity is a ‘big’ problem! In the UK, the proportion of people who are obese is steadily increasing. In 2010, the UK National Audit Office found that 26% of both men and women were obese (BMI >30).

  1. 30-40 = obese
  2. 40-50 = morbidly obese
  3. >50 = supermorbidly obese

We also know that it is very bad for your health. Even a fairly superficial literature search of obesity and it’s health consequences will reveal any number of studies implicating obesity as a risk factor for, or strongly associated with numerous diseases.

Amongst the many:

Type 2 diabetes mellitus
Gallbladder disease
Coronary artery disease
Restricted ventilation
Knee and hip osteoarthritis
Cancer (breast, endometrial, and colon)
Obstructive sleep apnoea (may be undiagnosed)
Soft tissue injury, infection, and low-back pain
Frequent falls and trauma

Why else is it a nightmare for us on ITU?


  • Difficult intubation
  • Reduced oxygen reserve (decreased ERV and FRC)
  • Failure of supraglottic devices
  • Failure of rescue techniques
  • Displaced/ poorly fitting tracheostomies
  • (NAP 4 and obesity)


  • Abdominal encroachment into the thoracic cavity
  • Fat deposition in the diaphragm and intercostal muscles
  • Reduced FRC, FEV1, MV and chest/lung compliance
  • V/Q mismatching and atelectasis


  • Difficulty with monitoring (ECG, NIBP, poor Echo windows)
  • Difficult vascular access


  • Differences in pharmacokinetics and under dosing of drugs is common. Important to monitor levels where appropriate


  • Significantly higher risk of DVT/PE
  • Data suggests that one should use a TBW dose of LMWH for prophylaxis


  • Should start enteral nutrition as soon as able.
  • Prone to protein breakdown due to elevated basal insulin levels                            
  • Most calories should be given as carbohydrate and a hypo caloric diet is suggested (decreased LOS and MV days)


  • Prone to skin and soft tissue infections
  • Increased risk of pressure ulcers (due to reduced skin integrity and difficulty with rolling)
  • Increased incidence of fungal infections

Transport and equipment issues

  • Appropriate bed and need for hoisting (safety issues for patient and staff)
  • Difficulties with investogations (poor quality XRs and technical challenges in CT/MRI)


More bad evidence!

A meta-analysis also found that a BMI ≥35 is associated with significantly higher all-cause mortality relative to normal weight (BMI 18.5-25). [Summary all-cause mortality hazard ratio = 1.29 (95% CI, 1.18-1.41).

Indeed, the UK National Audit Office has found that obesity is an important risk factor for the major chronic diseases that constitute the principal causes of death in England, such as heart disease, stroke, and some cancers.

As they are in the community, the implications of obesity are also profoundly negative in critical care..

Intensive care in the obese, a very complete article, details how the excess weight in obese patients puts them at risk of significant problems and complications during their intensive-care admission.

With the steady increase in the proportion of obese people in the population, the numbers admitted admitted to intensive care units is increasing accordingly. Research revealed that of 2878 patients admitted to 198 ICUs in 24 European countries, 36.4% (1047) were overweight [BMI 25-29.9], 14.7% (424) were obese [BMI 30-39.9] and 2.8% (81) were severely obese [BMI ≥40].

The possible problems for obese patients in the ICU are numerous and relate to virtually every organ system. There is a higher risk of generalised infection, including surgical site, ICU acquired and catheter-related. There is a greater potential for respiratory failure and increased risk of pneumonia and ARDS, as well as prolonged time on mechanical ventilation. Also, there is an increased risk of renal failure and multiple organ failure.

But…is it all bad!

In amongst all this gloomy / dismal research, there is a sliver of positivity. A recent editorial discussing obesity and survival in critically ill patients with ARDS, you will see talks of the ‘obesity paradox.’ this subject is becoming a huge area of interest, both for examination questions and research alike. Every conference you attend will contain something to do with this topic within the programme.

Despite obesity and overweight being associated with an increased risk of death, there are certain disease conditions in which a decrease in mortality have been reported. Specifically, septic shock and acute respiratory distress syndrome (ARDS). Hence the term obesity paradox.


Research investigating the obesity paradox in ARDS patients is available and fairly consistent.

In one meta-analysis carried out to determine the relationship between BMI and the acute outcomes of patients with ARDS, 5 trials with a total of 6268 patients were pooled and found that obesity and morbid obesity were associated with lower mortality in ARDS.

The results compared with normal weight:

  • Being underweight was associated with higher mortality (OR 1.59, 95% confidence interval (CI) 1.22, 2.08, P = 0.0006)
  • Obesity and morbid obesity were more likely to result in lower mortality (OR 0.68, 95% CI 0.57, 0.80, P < 0.00001; OR 0.72, 95% CI 0.56, 0.93, P = 0.01)

Another meta-analysis investigated the relationship between obesity, ARDS/ALI risk and mortality. 24 studies including 9,187,248 patients were analysed. The results demonstrated that although obesity was an important risk factor for ARDS / ALI, the outcomes in that population were improved compared to patients with a normal body mass index.

The combined results from 16 studies examining the effect of obesity on morbidity from ARDS/ALI showed an 89% increase in odds ratio (pooled odds ratios (OR) 1.89, 95% confidence intervals (CI) 1.45 to 2.47).

A subgroup analysis found that, compared to normal weight, obesity was associated with an increased risk of ARDS/ALI (OR1.57, 95% CI 1.30–1.90 for obese (BMI30-39.9kg/m2); OR1.75, 95% CI 1.42–2.15 for obese (BMI≥30kg/m2); OR1.67, 95% CI 1.04–2.68 for morbid obese(BMI≥40kg/m2)).

While, obesity was significantly associated with reduced risk of ARDS/ALI mortality (OR0.88, 95% CI 0.78–1.00 for overweight(BMI≤18.5m2); OR0.74, 95% CI 0.64–0.84 for obese (BMI30-39.9kg/m2); OR0.84, 95% CI 0.75–0.94 for 60days mortality; OR0.38, 95% CI 0.22–0.66 for 90days mortality).

Both meta-analyses have some limitations, including:

  • Inclusion of retrospective studies
  • Cofounders not adjusted
  • Heterogeneity in some of the analyses


So why is it ‘protective’??!

This is described as a paradox for good reason. With the background knowledge and evidence of what obesity can do to you, it’s not surprising that billions is thrown into combatting it! So how can something so ‘bad’, actually be good on occasion?!

What does fat do for us?

  • Vital energy substrate
  • Vital for ALL cell membranes in our bodies
  • Vital substrate for all of those pesky inflammatory mediators we are always trying to fight off in sepsis – but without them, pathogens would get the better of us!
  • Acts as a moderator of inflammatory gene expression
  • Important for endothelial function and vascular integrity
  • Vital for hormone function and production – adipokines (adiponectin / leptin) and steroid hormones
  • Carriage of fat soluble vitamins
  • Protective cushion for organs
  • Insulation and heat production
Screen Shot 2017-06-15 at 15.49.40.png
Fat and inflammatory mediators
Screen Shot 2017-06-15 at 16.01.15
The Basics!
Screen Shot 2017-06-15 at 15.57.12
Pro-inflammatory state in obesity
Screen Shot 2017-06-15 at 15.55.12
Theories behind obesity related diseases
Screen Shot 2017-06-15 at 16.36.14
Complex metabolic pathway – cannon fodder to go wrong in critical illness!

Screen Shot 2017-06-15 at 16.52.11.png

In terms of what might explain this decreased mortality in obese patients with ARDS.

Here are some theories:

  • Protective ‘pre-conditioning cloud’ in obesity – the increased plasma and adipose levels of inflammatory cytokines induces a chronic inflammatory state. This pre-existing low-grade inflammation limits the deleterious effect of any secondary inflammatory response, such as one precipitated by a lung injury or sepsis.
  • Bacteria appear to dislike HDL immensely! Obese patients may have higher circulating cholesterol levels, and within this makeup is HDL (as well as the LDL we have all grown up to dislike!).
  • Paradoxically, cholesterol levels fall in critical illness and thus, perhaps those of normal BMI standing / those with malnutrition or low BMI in particular fair worse? Obese patients effectively wear a ‘Protective G-suit’, against ARDS.
  • Statins – it may well be that those on statins have a ‘better’ more anti-inflammatory lipid profile than those who are not. This could explain what we have seen over the years regarding statins being ‘protective’ to the critically ill. But…it’s one those who have been on them for some time pre-morbidly.

Screen Shot 2017-06-15 at 15.53.55.png


The future?

Perhaps we will be administering synthetic cholesterol and resolvin?

Even LDL, the once enemy of the lipid profile has been found to have benefits!

Screen Shot 2017-06-15 at 16.40.52

High LDL-C is inversely associated with mortality in most people over 60 years. This finding is inconsistent with the cholesterol hypothesis (ie, that cholesterol, particularly LDL-C, is inherently atherogenic). Since elderly people with high LDL-C live as long or longer than those with low LDL-C, our analysis provides reason to question the validity of the cholesterol hypothesis. Moreover, our study provides the rationale for a re-evaluation of guidelines recommending pharmacological reduction of LDL-C in the elderly as a component of cardiovascular disease prevention strategies.

Perhaps we are a little harsh in being historically ‘fattest’ in medicine…well, we are perhaps where ARDS is concerned anyway. You cannot go against the time old evidence that obesity is bad for many reasons, but this is a rightly ‘huge’ subject worth further research, don’t you agree?

Also see:

Basics of lipid metabolism

Statins and ARDS

The Obesity paradox [Editorial]

HDL and inate immunity

HDL and sepsis





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