Tight glycemic control may favor fibrinolysis in patients with sepsis.
OBJECTIVE
To investigate whether tight glycemic control, in patients with sepsis, may restore a normal fibrinolysis by lowering plasminogen activator inhibitor (PAI)-1 levels.


METHODS
Prospective randomized clinical trial.


METHODS
Three Italian university hospital intensive care units.


METHODS
Ninety patients with severe sepsis/septic shock.


METHODS
Patients were randomized to receive either tight glycemic control (treatment group, target glycemia, 80-110 mg/dL) or conventional glycemic control (control group, target glycemia, 180-200 mg/dL).


METHODS
Inflammation, coagulation, and fibrinolysis markers were assessed, along with Sepsis-related Organ Failure Assessment scores, >28 days.


RESULTS
In the whole population, at enrolment, inflammation and coagulation were activated in >80 of 90 patients, whereas fibrinolysis, as assessed by PAI-1 activity and concentration, was impaired in only 34 patients. The extent of the inflammatory reaction or of the coagulation activation was unrelated to outcome. In contrast, 90-day mortality rate of the 34 patients in whom fibrinolysis was definitely inhibited at study entry was twice that of the 56 patients in whom fibrinolysis was intact (44% vs. 21%, p = 0.02). After randomization, during the study, daily glycemia averaged 112 +/- 23 mg/dL in the treatment group and 159 +/- 31 mg/dL in controls (p < 0.001), with total daily administered insulin 57 +/- 59 IU and 36 +/- 44 IU, respectively (p < 0.001). A small, but significant, enhancement of fibrinolysis could be observed in the treatment group, as indicated by the time course of PAI-1 activity (p < 0.001), PAI-1 concentration (p = 0.004), and plasmin-antiplasmin complexes (p < 0.001). Morbidity, rated with the Sepsis-related Organ Failure Assessment score, became significantly lower (p = 0.03) in the treatment group.


CONCLUSIONS
Fibrinolysis inhibition, in severe sepsis/septic shock, seems to have a relevant pathogenetic role. In this context, tight glycemic control seems to reduce, with time, the fibrinolytic impairment and morbidity.
Savioli
Monica
M
Dipartimento di Anestesia, UO di Anestesia e Rianimazione, Rianimazione Intensiva e Subintensiva e Terapia del Dolore, Fondazione IRCCS, Ospedale Maggiore Policlinico, Mangiagalli, Regina Elena di Milano, Milan, Italy.
Cugno
Massimo
M
Polli
Federico
F
Taccone
Paolo
P
Bellani
Giacomo
G
Spanu
Paolo
P
Pesenti
Antonio
A
Iapichino
Gaetano
G
Gattinoni
Luciano
L
D000328:Adult; D000368:Aged; D015415:Biomarkers; D001786:Blood Glucose / Q000032:analysis*; D005260:Female; D005342:Fibrinolysis; D006785:Hospitals, University; D006801:Humans; D007003:Hypoglycemia / Q000188:drug therapy / Q000453:epidemiology; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007249:Inflammation / Q000503:physiopathology; D007328:Insulin / Q000008:administration & dosage / Q000627:therapeutic use; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011446:Prospective Studies; D018805:Sepsis / Q000097:blood* / Q000503:physiopathology; D012772:Shock, Septic / Q000097:blood / Q000503:physiopathology
D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1