Abstract
BackgroundMottling 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.MethodsThis 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.ResultsWe 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.ConclusionMottling 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.
Highlights
Mottling around the knee, reflecting a reduced skin blood flow, is predictive of mortality in patients with septic shock
There was no difference in baseline skin blood flow in the forearm area between patients with sepsis and Discussion Using validated non-invasive technology comprising laser Doppler flowmetry coupled with Ach iontophoresis, we demonstrated heterogeneous skin endothelial dysfunction in critically ill patients with severe infections
The endothelial function in forearm skin did not differ between survivors and non-survivors, suggesting that vasopressor doses were not directly responsible for the difference between the two groups in the skin endothelial response in the knee area. This is the first demonstration that mottling is associated with skin regional endothelial dysfunction in septic shock
Summary
Mottling around the knee, reflecting a reduced skin blood flow, is predictive of mortality in patients with septic shock. Mottling, defined as patchy skin discoloration, reflects reduced skin blood flow [6] and low tissue oxygen saturation [7] and has been suggested as a tool for clinical evaluation of tissue perfusion in patients with severe infection [8]. Extensive mottling extension has been demonstrated to be predictive of mortality in patients with septic shock, independently of systemic haemodynamic. The mechanism responsible for the specific regional reduction of blood flow in the mottled skin area remains unknown. Direct capillary obstruction by platelet aggregation and coagulation cascade activation has been suggested as a mechanism responsible for skin hypoperfusion [11] and has been documented in patients with meningococcemia [12]. In the absence of diffuse intravascular coagulation, the widely accepted concept is vasoconstriction mediated by major sympathetic neuroactivation [13]
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