Physiologic consequences of burns

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In general, burns questions from the fellowship exam tend to have a strong "airway" flavour to them. Physiological consequences of burns as a broad topic has not been asked about. For instance, Question 26 from the first paper of 2012 is concerned mainly with the effects on the respiratory system. This question is well answered by the Burns, Oxygenation and Ventilation page from the LITFL CCC; as an exam-oriented summary this resource leaves little to be desired. The chapter stretching below trends more towards rant than summary, and is offered as an extended footnote to the CCC page and the college model answer to Question 26.

Additional attention to thermal injury is found in burns-related chapters within the "Trauma, Burns and Drowning" revision topic area:

• Airway burns and smoke inhalation injuries
• Fluid resuscitation for the burns patient
• Emergency management of severe burns
• Heat stroke

Consequences of airway burns

Question 30 from the second paper of 2009, Question 28  from the second paper of 2010 and Question 11 from the first paper of 2013 were all essentially identical investigations of the candidate's ability to recall the features of airway burns, This topic is discussed at length in a dedicated chapter on airway burns.

A BMJ article from the "ABC of burns" series contains Table 1, "Warning signs of airway burns", which I reproduce below:

• Burns occurred in an enclosed space
• Stridor, hoarseness, or cough
• Burns to face, lips, mouth, pharynx, or nasal mucosa
• Soot in sputum, nose, or mouth
• Dyspnoea, decreased level of consciousness, or confusion
• Hypoxaemia (low pulse oximetry saturation or arterial oxygen tension) or increased carbon monoxide levels (>2%)

Influence of burns on gas exchange and ventilation

Impaired ventilation

• Decreased respiratory effort due to a decreased level of consciousness
• Poor lung expansion resulting in a restrictive ventilatory defect, due to the presence of circumferential torso burns (or even non-circumferential)
• Poor air entry due to upper/lower airway burns; an obstructive pattern of ventilation
• Decreased lung compliance due to pulmonary thermal injury, ensuing pulmonary oedema and ARDS
  • Pulmonary oedema could also be due to the vigorous fluid resuscitation
  • ARDS could also be due to the SIRS which results from widespread burns.

Impaired diffusion of gases

• Decreased gas exchange due to increased pulmonary interstitial and alveolar fluid, due to pulmonary thermal injury

Increased shunt fraction

• Increased shunt fraction due to collapse of oedematous lungs
• Increased shunt fraction due to airway swelling, obstruction and subsequent atelectasis
• Increased sputum retention and increased risk of pneumonia due to epithelial damage and impaired mucociliary escalator function.

Impaired oxygen transport and mitochondrial metabolism

• Decreased oxygen delivery to tissues, due to:
  • Metabolic/respiratory acidosis and consequent right shift of oxygen-haemoglobin dissociation curve
  • Carbon monoxide poisoning
• Decreased oxygen utilisation due to cyanode poisoning

Circulatory and cardiovascular consequences of burns

Early : hypovolemic shock

• This is a stereotypical response to the loss of circulating volume, similar to the physiologic response to the loss of blood.
• It is characterised by intravascular volume depletion, low pulmonary artery occlusion pressures, elevated systemic vascular resistance, and depressed cardiac output.
• Specifically, the systemic vascular resistance increases by up to 200% , and the cardiac output is halved (Asch et al, 1973).
  The cardiac output decrease is partly due to the volume depletion, and partly due to the mitochondria-impairing effects of circulating TNF-α.
• With resuscitation, these parameters seems to normalise by day 3, and the circulation becomes hyperdynamic by day 5. Circulating vasopressin levels seem to correlate with the timing of these changes: vasopressin concentration quickly rises 50-fold, and drops to near-normal levels at around 5 days after the burn injury (Crum et al, 1990).

Pathophysiology of burns-associate hypovolaemia

• The best summary of this comes from a 2011 paper by Barbara Latenser (2009). I paraphrase her here:
• Loss of vessel wall integrity in the microciculation
• Exudate of proteins into the interstitium
• Most of this occurs locally at the burn site and is maximal at 24 hrs postinjury
• Drop in systemic intravascular colloid osmotic pressure results from intravascular protein loss
• Rise in interstitial protein concentration due to cell lysis and transmigration of serum proteins out of leaky capillaries.
• Massive fluid movement into the interstitium is therefore caused by a combination of the sudden decrease in interstitial pressure, an increase in capillary permeability to protein, and an imbalance in hydrostatic and oncotic forces favoring the fluid movement into the interstitium.
• Thus, intracellular and interstitial compartments increase in volume at the expense of plasma and blood compartments.
• This manisfests as a loss of circulating plasma volume and haemoconcentration.

Late : hyperdynamic circulation and increased cardiac output

• This phenomenon is driven by a catacholamine surge; the urinary catecholamine product levels increase by 10 to 20-fold in these patients (Wilmore et al, 1974)
• The increase in the cardiac output is thought to be a part of the profound hypermetabolic response which is directly proportional to the size of the burn (Williams et al, 2011); it is most frequently seen in patients who have suffered a burn injury in excess of 40% of their body surface area.
• Marked tachycardia is seen; the resting heart rate may double.
• Increased myocardial oxygen consumption is to be expected.
• Cardiac output, at least in paediatric patients, plateaus at around 150% of the normal values, and is still about 140% by the time of discharge.
• In the cohort followed up by Williams et al, this increase in cardiac output persisted up to two years, long after the original injuries had healed.

Regional changes: limb compartment syndrome and the need for escharotomy

Question 18 from the second paper of 2012 presents the candiates with a pair of burned-looking legs, and asks what the complications of such burns might be. Compartment syndrome is on the top of the list.

• A third or second degree (full or partial thicknes) burn is assentially an inelastic cuff of oedematous tissue which expands gradually over the first few days.
• During this time, the patient is also filled overflowing with resuscitation fluid, which contributes to muscle oedema in the muscle underlying that swelling cuff.
• The result is initially a decrease in capillary perfusion, which can lead gradually to tissue damage by ischaemia.
• Venous flow is impaired, and thrombosis develops.
• Ischaemia affects nerves, and paraesthesia occurs - usually this is the first sign that a compartment syndrome is developing
• In rare instances there is sufficient swelling to actually halt arterial flow.
• Amputation may be required

Neurological and psychological consequences of burns

Severe pain at rest and with dressing changes

This is one of those areas of burns management which has become the subject of numerous books and PhD theses. Instead of linking to those, I will instead offer a link to some pragmatic guidelines from www.vicburns.org.au. Another excellent resource is this 2004 review article by Norman and Judkins.

Major mechanisms of pain in the setting of burns:

• Stimulation of skin nociceptors that respond to heat (thermoreceptors)
• Mechanical distortion of mechanoreceptors
• Endogenous noxious chemicals eg.  histamine, serotonin, bradykinin
• Primary hyperalgesia (the release of inflammatory mediators sensitizes the active nociceptors )
• Secondary hyperalgesia (continuous stimulation of nociceptive afferent fibres leads to increased sensitivity in surrounding unburned areas - this is a spinal thing)

Key features of a successful approach:

• Pre-emptive, multimodal analgesia
• Combination of drugs,  regional nerve block and non-pharmacological methods
• Opioids plus NSAIDs are the best approach
• Opioid-sparing drugs eg. paracetamol, clonidine
• Ketamine and methoxyflurane for dressing changes

Direct electrical burn damage of the central nervous system

It is extremely rare for a common house fire to burn somebody's brain, given that its defence has been a priority from an evolutionary standpoint. Not so for electical burns, however. The path taken by electricity is often going to involve the brain and spine (as these are highly vascular, and vascularity is what largely determines conductivity). The immediate result is usually coma; similarly to the effects of defibrillation on the myocardium, all the voltage-gated channels open in the wake of a large current, and the consequence is a simultaneous depolarisation of all involved neurons. This manifests as a seizure, and a post-ictal stupour usually ensues.

A review of 90 consecutive electrical burns cases (Grube et al, 1990) has revealed that even severe electrical injury to the CNS is likely to be well tolerated in the long term. I quote Baiba Grube directly:

• Low-voltage injuries are unlikely to leave permanent sequelae
• Immediate coma usually resolves, unless associated with anoxia
• Acute peripheral neuropathies associated with high-voltage injury are likely to improve
• Delayed neuropathies are fairly common, are less likely to resolve, but are generally mild
• Delayed central or spinal cord lesions are uncommon.

Psychological and behavioural changes due to severe burns

Like most trauma-exposed people, the burns patients tend to develop various new psychological problems, and their pre-existing issues are amplified (Van Loey et al, 2003)

• Post-traumatic stress disorder ( incidence of 30-45%) as a consequence of prolonged hospitalisation and frequent dressing changes
• Depression / anxiety / demoralization, loss of social network, loneliness, and bereavement - all as a consequence of disfiguring injuries (incidence of 20-65%)
• Neuropsychological problems associated with the prolonged exposure to heavy sedation and multiple anaesthetics (eg. short term memory problems, decreased concentration)
• Sexual dysfunction (at least in part due to the replacement of large areas of skin with insensate scar tissue)

Biochemical electrolyte-related consequences of burns

Loss of electrolytes by means of exudate

The average severe burns patient is covered in numerous dressings, and they are getting soaked with exuduate. In the 1950s, Moore at al collected these exudate-encrusted dressings and analysed them to estimate the electrolyte losses of  burns patients. In short, exudate fluid largely resembles plasma, and the proportion of lost electrolytes resembles the loss of blood volume, and its diluting replenishment by pure water.

• Sodium and chloride are lost - approximately 50% of the daily sodium losses are through the exudate.
• Phosphate and calcium are also usually low (Hauhouot-Attoungbre et al, 2005)
• Potassium is lost - it is ultrafiltered out of the burned tissue, and unlike the tubules there is no mechanism to reclaim it. However the serum potassium of burns patients is usually high, for other reasons.

Hyperkalemia associated with suxamethonium

Hyperkalemia associated with giving sux to burns patients is a well documented phenomenon, and ebveybody ends up having to memorise it as one of the contraindications for giving sux, no matter which primary exam they sat. It has been known about for some time (Schaner et al, 1969). The problem seems to have more to do with prolonged immobility than with the burn itself (Van Loey et al, 2003)

Renal impairement due to burns

If you think about it, there are a hundred reasons for the kidneys to go off in this setting, and none of them are specific to the actual thermal injury. The following is a short list of reasons as to why a shocked patient might develop renal failure. According to Chrysopoulo et al (1999) the incidence of this may be around 5% (in a retrospective case series).

• Hypovolemic shock state
• Sepsis
• Rhabdomyolysis
• Abdominal compartment syndrome (circumferential torso burns)
• Massive haemolysis may result in haemoglobinuria and acute tubular necrosis.

On a more exotic note, one might find their burns patient having a raise urea due to excess protein catabolism. 

Impairement of thermoregulation

One need not dwell on this issue overlong; it is clear that the skin is one's main heat exchange surface, and with the loss of a large area of skin one also loses one;s ability to control the exchange of body heat with the external environment. Moreover, there is a constant loss of warm fluid in the form of exudate, which is exchanged with dressings. Secretions deliver water to the surface of the wounds and into dressings, or the dressings themselves may be soaked with saline - either way, the water evaporates, robbing the patient by convective loss. In the acute setting, it is important to remember that the burns patient is likely to receive up to 25% of their body weight in resuscitation fluid which might all be at room temperature.

In short, hypothermia is to be expected.

Endocrine metabolic and nutritional effects of burns

Hypermetabolic state

This is a chronic inflammatory state which persists for months. It starts around the fifth day after the burn. Herndon et al (2004) describe these abnormalities in an excellent article from the Lancet. The following are its characteristic features:

• Increased body temperature
• Increased total body oxygen consumption (i.e. an increased O₂ER),
• Increased glucose use and CO₂ production,
• Increased glycogenolysis, proteolysis and lipolysis
• Not to mention the continuous exudative loss of protein (Moore et al, 1950)
• Futile substrate cycling
• Overall, a hypercatabolic hypermetabolic state

This endocrine abnormality is partly due to the release of cortisol and partly due to the catecholamine excess which is associated with recovery from severe burns. But wait, you might say: can't you β-block those,  and make it all go away? You'd be right. Indeed, Herndon et al (2001) have published a randomised controlled trial (25 children, half randomised to receive propanolol) which demonstrated precisely that. The β-blocked children were substantially less protein-wasted after two weeks of propanolol - their fat-free body mass did not decrease at all, whereas the untreated children lost 9% of theirs.

Stress-related hormone changes

• Increased cortisol for the first 3 weeks
• Decreased T4, acutely
• Decreased testosterone, in the chronic recovery phase
• Decreased growth hormone in the chronic recovery phase

Fatty liver infiltration and hepatomegaly

• For some reason, the size of the liver acutely doubles ( Jeschke et al, 2008). This is mentioned as a mere footnote, and not well explained. The liver stays enlarged and is still enlarged at discharge from the ICU. Fatty infiltration appears to be the culprit. The same author remarks that fat transporter proteins are decreased after a burn burn while triglycerides and free fatty acids are increased.

Haematological consequences of burns

Intravascular haemolysis

Lawrence et al (1993) found patients with "massive" burn injury developed haemolysis. None of the patients in this paper survived long than three days. I cannot get hold of this paper in full text, but it seems the "massive" burns were truly massive - one of the patients didn't last more than 45 minutes. One might surmise that the haemolysis is the direct action of extreme heat on a large proportion of the bloodstream. In olden days, haemolysis in burns was seen more frequently because the patients frequently received poorly matched blood products (Topley ey al, 1963)

Pseudothrombocytosis

This arises in haemolysis. The automated cell counter becomes "confused" by multiple red cell fragments and incorrectly recognizes them as platelets, hence the pseudo.

Disseminated intravascular coagulation (DIC)

In an audit of Finnish burns patients, Kallinen et al (2012) identified DIC in 10% of severe burns patients. This seems to be a manifestation of severe SIRS in most cases. In the most severe of burns, DIC may be caused by the appearance of burned cellular debris in the circulation (Lippi et al, 2010)

Infectious complications of burns

Not just entire book chapters, but entire books have been written on this topic. Probably the most succinct resource on it would have to be the UpToDate article. To the penniless public, I will also recommend the free online 2006 article by Deirdre Church, from Clinical Microbiology Reviews - it is ridiculously detailed. The CICM examiners ultimately decided that this was a good topic of discussion for Question 7 from the second paper of 2022, which asked about the risk factors, local signs, systemic features and diagnostic challenges of identifying infection in patients with thermal injuries.

Immune compromise

• The human sknin is the most important host defence you have against infection, and burns represent a substantial breach of this barrier
• Significant thermal injuries induce a state of immunosuppression
• This is only partially due to the stress reponse (i.e. endogenous cortisol)
• Lymphocyte inactivity - more specifically, anergy - is seen after burns (Wolfe et al, 1982) and the mechanism of this is not well understood.

Wound colonisation in patients with burns

• Immediately after a burn, the microbial population is sparse (as recently they all got burned)
• Soon after a burn, staphylococci and other gram-positive bugs come out of their hidden bunkers (they are the most likely to have survived thermal injury by hiding in hair follicles and sweat glands)
• The flora of the first week is a mixed gram positive and negative growth, many of them hospital-acquired; S.aureus and enterococci are the dominant species
• After the first week, gram negatives tend to dominate the scene, with Pseudomonas the clear winner.
• With prolonged hospital stay and multiple courses of broad-spectrum antibiotics, fungal species begin to take over. The remaining bacterial agents consist of such indestructable extremophiles as Stenotrophomonas, Acinetobacter and Serratia.

Wound infection in patients with burns

• Not all colonised wounds are infected. However, you dont want to miss an infection. 75% of burns mortality seems to be due to sepsis.
• Invasive wound infection is characterised by:
  • Foul odour
  • Separation of eschar
  • Surrounding oedema and cellulitis
  • Progression of the burn, i.e. the development of full-thickness necrosis in an aea previously affected by only partial thickness burns.
• Systemic antibiotics are reserved for patients demonstrating burn wound cellulitis or sepsis.

Risk factors for wound infection in patients with burns

From UpToDate:

• Burn factors:
  • More than 20% BSA burns
  • Depth of burn
  • "age" of burn (delay to treatment)
• Patient factors:
  • Extremes of age
  • Impaired immunity
• Pathogen factors
  • Type and number of organisms
  • Heavy colonisation (bacterial counts over 10⁵ organisms per g of eschar)
  • Enzyme and toxin production
  • Motility
• Therapeutic factors:
  • Delays in burn wound excision
  • Topical therapy (instead of excision)

Clinical features of wound infection in patients with burns

Local signs:

• Purulent drainage
• Foul odour
• Oedema and warmth
• Surrounding erythema
• Tenderness or increased pain
• Unexpectedly rapid separation of the eschar
• Conversion of an area of partial-thickness injury to full-thickness necrosis, or the appearance of necrosis in previously viable tissue
• Haemorrhagic discoloration of subeschar tissue

Systemic features:

• Fever or hypothermia
• Progressive tachycardia
• Refractory hypotension
• Increasing FiO2 requirements

The ABA has a somewhat contested set of criteria, on which the above is based.

Diagnostic challenges in identifying thermal injury wound infection

• Identification of local infection
  • Wound appearance is often obscured by dressings
  • The appearance of burns makes it difficult to identify infected tissue (eg. everything is oedematous and red)
  • Pathology speciments will inevitably grow organisms
  • Discriminating between colonisation and infection is difficult; not every lab may be able to do quantitative cultures
  • Pathogenic organisms (eg. some fungi) may not grow easily on normal culture media (Lago et al, 2021)
• Identification of systemic infection
  • The systemic response to burn injury mimics sepsis
  • Inflammatory markers (eg. WCC, CRP, procalcitonin) will be elevated even in wound colonisation
  • The patient may have infection elsewhere (eg. VAP), i.e. the wound is not the source