Jeschke 2008 - Ann Surg - Pathophysiology paediatric

Summary

This prospective cohort study aimed to characterize the pathophysiologic response to severe burn injury in 242 pediatric patients with burns over 30% of total body surface area (TBSA). The average age was 8 years old, average TBSA burned was 56% with 43% being third degree burns. Length of hospital stay averaged 31 days (0.55 days per %TBSA burned). Patients underwent surgery every 8 days on average and had 4 operations during hospitalization. Mortality rate was 8%.

Key findings:

Hypermetabolism

• Resting energy expenditure (REE) was elevated immediately after burn, peaking at 130-140% of predicted at 2 weeks postburn. REE remained significantly elevated at discharge indicating persistent hypermetabolism.

Muscle protein metabolism

• Peripheral muscle protein synthesis was unchanged but breakdown was increased 3-4 fold at 1 and 3 weeks postburn leading to negative protein balance and loss of lean body mass.

Body composition changes

• From admission to discharge, patients lost 5% lean body mass, 3% bone mineral content, and 2% bone mineral density. Total fat mass and body fat percentage increased by 3% and 7% respectively.

Inflammation

• Serum acute phase proteins (C3, α2-macroglobulin, haptoglobin, α1-acid glycoprotein, CRP) were elevated up to 10-fold. Hepatic constitutive proteins (pre-albumin, transferrin) were decreased 4-8 fold.

• 17 cytokines were significantly elevated, especially IL-6, IL-8, MCP-1, MIP-1β (100-200 fold increase).

Hormonal changes

• IGF-1, IGFBP3, and GH were decreased.

• T4 and thyroid index were decreased initially but recovered.

• Cortisol and urine cortisol were increased 5-7 fold acutely.

• Estrogen decreased initially then increased while testosterone decreased from week 4 onwards.

Glucose metabolism

• Glucose was increased with high insulin levels indicating insulin resistance and hyperglycemia.

Bone metabolism

• Osteocalcin and PTH were decreased 5-7 fold indicating severe impairment of bone metabolism.

Cardiac changes

• Cardiac index, output and heart rate were increased up to 160% of predicted initially and remained elevated.

Liver

• Liver size doubled immediately postburn and remained enlarged throughout hospitalization.

In summary, this large study shows that major burns over 30% TBSA induce a profound inflammatory, hypermetabolic, catabolic response lasting over a month. The greatest changes occurred in metabolism, muscle protein balance, inflammation, body composition, hormones, cardiac function, and liver size. This persistent pathophysiologic response contributes to long term morbidity and disabilities. Understanding these derangements can help guide targeted treatments to attenuate the metabolic response, reduce muscle wasting, optimize nutrition, modulate inflammation, improve wound healing, and potentially improve outcomes in severely burned patients.