Impaired bone healing in multitrauma patients is associated with altered leukocyte kinetics after major trauma

Figures & data

Figure 1 Peripheral blood counts of leukocytes (A), neutrophils (B), monocytes (C), and thrombocytes (D) during the first 2 weeks after major trauma.

Notes: Patients with normal (green) and impaired (red) fracture healing of the tibia. The peripheral blood-count curves of leukocytes, neutrophils, monocytes, and thrombocytes were analyzed with mixed linear models, and differed significantly between healing groups during the first 2 weeks after trauma (P-values were 0.0122, 0.0083, 0.0204, and <0.0001, respectively). In addition, each separate time point was compared between outcome groups using an independent t-test or nonparametric equivalent. For these subanalyses: *P<0.05; **P<0.01; ***P<0.001. Gray bars represent reference values.

Abbreviation: SEM, standard error of mean.

Figure 2 Peripheral blood lymphocyte counts (A), hemoglobin values (B) and the percentage of patients that required blood testing on each day (C) during the first two weeks after major trauma for patients with normal (green) and impaired (red) fracture healing of the tibia.

Notes: The peripheral blood lymphocyte counts and hemoglobin values were analyzed with mixed linear models, and these analyses showed no significant differences between the healing groups (P-values 0.0688 and 0.9275, respectively). In addition to the analyses with mixed linear models, each separate time point was also compared between outcome groups using an independent t-test or nonparametric equivalent. For these subanalyses: **P<0.01. Gray bars represent reference values.

Abbreviation: SEM, standard error of mean.

Table 1 Overview of clinical parameters of patients with normal and impaired fracture healing of the tibia

	All patients, n=80	Normal healing, n=48 (60%)	Impaired healing, n=32 (40%)	P-value
Age	40 [24–55]	37 [24–58]	42 [25–54]	NS
Sex	58% male	54% male	63% male	NS
Injury severity Score	25 [19–34]	25 [18–34]	24 [19–33]	NS
New Injury severity Score	27 [22–41]	31 [22–34]	27 [22–41]	NS
Number of fractures	4 [2–5]	3 [2–5]	4 [2–6]	NS
Tibia-fracture localization
– proximal	20%	20%	19%	NS
– shaft	49%	48%	52%	NS
– distal	31%	32%	29%	NS
Type of tibia fracture (AO)
– multifragmentary/complex	37%	32%	45%	NS
– intra-articular	31%	32%	29%	NS
Soft-tissue injury (Gustilo)
– 0 closed fracture	59%	69%	44%	0.037
– I wound <1 cm	14%	13%	16%	NS
– II wound >1 cm with moderate soft tissue damage	15%	10%	22%	NS
– III wound >1 cm with
➢IIIa adequate soft-tissue cover	6%	6%	6%	NS
➢IIIb inadequate soft-tissue cover	5%	2%	9%	NS
➢IIIc associated arterial injury	1%	0%	3%	NS
Time until tibia fixation (days)	0 [0–5]	0 [0–5]	1 [0–6]	NS
Type of fixation
– nonoperative	11%	19%	0%	0.010
– ORIF	43%	44%	41%	NS
– nail (ETN, UTN, or CTN)	44%	38%	53%	NS
– external	3%	0%	6%	NS
Number of operations	2 [1–4]	2 [1–3]	2 [1–5]	NS
ICU stay (days)	0 [0–8]	1 [0–9]	0 [0–7]	NS
	5.1 (8.3)	4.9 (7.5)	5.4 (9.4)
Hospital stay (days)	27 [14–50]	27 [14–50]	28 [12–46]	NS
Complications	56%	56%	56%	NS
– infectious	41%	44%	38%	NS
– sepsis	9%	8%	9%	NS
– noninfectious	31%	27%	38%	NS
Delayed union	16%	–	41%	–
Nonunion	24%	–	59%	–
– atrophic	–	–	47%	–
– hypertrophic	–	–	53%	–

Note: Data shown as median ± [interquartile range] or mean ± (standard deviation).

Abbreviations: NS, not significant; AO, arbeitsgemeinschaft für Osteosynthesefragen (association for study of internal fixation); ORIF, open reduction internal fixation; ETN, expert tibial nail; UTN, unreamed tibial nail; CTN, cannulated tibial nail; ICU, intensive care unit.

Figure 3 Our hypothesis of the mechanism through which an aberrant systemic immune response to trauma impairs fracture healing.

Note: The green boxes describe a physiological systemic immune response to major trauma, and the red boxes describe a different detrimental systemic immune response.