Marked regional endothelial dysfunction in mottled skin area in patients with severe infections

Abstract

Background: Mottling around the knee, reflecting a reduced skin blood flow, is predictive of mortality in patients with septic shock. However, the causative pathophysiology of mottling remains unknown. We hypothesized that the cutaneous hypoperfusion observed in the mottled area is related to regional endothelial dysfunction.

Methods: This was a prospective, observational study in a medical ICU in a tertiary teaching hospital. Consecutive adult patients with sepsis admitted to ICU were included. After resuscitation, endothelium-dependent vasodilation in the skin circulation was measured before and after iontophoresis of acetylcholine (Ach) in the forearm and the knee area. We analyzed the patterns of induced vasodilatation according to the presence or absence of mottling and vital status at 14 days.

Results: We evaluated 37 septic patients, including 11 without and 26 with septic shock. Overall 14-day mortality was 22%. Ten patients had mottling around the knee (10/37, 27%). In the knee area, the increased skin blood flow following iontophoresis of Ach was lower in patients with mottled skin as compared to patients without mottled skin (area under curve (AUC) 3280 (2643-6440) vs. 7980 (4233-19,707), both P < 0.05). In the forearm area, the increased skin blood flow following iontophoresis of Ach was similar in patients with and without mottled skin. Among patients with septic shock, the increased skin blood flow following iontophoresis of Ach in the knee area was significantly lower in non-survivors as compared to survivors at 14 days (AUC 3256 (2600-4426) vs. 7704 (4539-15,011), P < 0.01). In patients with septic shock, the increased skin blood flow in the forearm area following iontophoresis of Ach was similar in survivors and non-survivors at 14 days.

Conclusion: Mottling is associated with regional endothelial dysfunction in patients with septic shock. Endothelial dysfunction in the knee skin area was more pronounced in non-survivors than in survivors.

Keywords: Endothelial function; Infection; Mortality; Mottling; Tissue perfusion.

Fig. 1

Example of skin microcirculatory blood flow assessment in a patient without mottling (Patient n°1) and in a patient who had mottling in the knee area (Patient n°2). Skin blood at baseline and after iontophoresis acetylcholine was measured on the forearm area (a) and in the knee area (b)

Fig. 2

Analysis of skin microcirculatory blood flow in patients with knee mottling (n = 10) and in patients without knee mottling (n = 27) at 6 h. Skin blood flow was assessed on the forearm and the knee areas at baseline (a, b), and after acetylcholine iontophoresis (peak value (c and d) and area under curve (auc) (e and f). *P < 0.05. PU perfusion units

Fig. 3

Analysis of skin endothelial function in the knee area according to mottling score. Skin blood flow was quantified after acetylcholine iontophoresis. P = 0.02, Kruskal-Wallis test. AUC area under curve

Fig. 4

Analysis of skin microcirculatory blood flow measured in three groups of patients: patient with sepsis (n = 11), 14-day survivors with septic shock (n = 18), and 14-day non-survivors with septic shock (n = 8). Skin blood flow was quantified on the forearm and the knee area at baseline (a, d) and after acetylcholine iontophoresis (peak value (b and e) and area under the curve (AUC) (c and f). *P < 0.05, **P < 0.01. PU perfusion units

Fig. 5

Examples of skin microcirculatory blood flow measurements in the knee area in three patients (one with sepsis, one 14-day survivor with septic shock, and one non-survivor with septic shock) on the forearm and the knee area at baseline and after acetylcholine iontophoresis