Of the 416 eligible patients, 388 patients were included in the intention-to-treat (ITT) analysis and 386 in the per-protocol analysis (Figure ). The groups were comparable in terms of demographics (except a slightly younger age in the MICO group and greater weight in the control group; Table ), type of admission (surgical vs. medical), main admission diagnosis categories, presence of infection at admission, baseline hemodynamics, severity of illness (Table ), and presence of organ dysfunctions at baseline (see Additional file 1
/Table ). Also, the time spent in the hospital before admission to the ICU and the time from ICU admission to arterial line insertion and study baseline were comparable (Table ). Sixty-one percent of patients were admitted to the ICU within 24 hrs of hospital admission, 42% within six hours, and 20% within one hour.
Study flowchart. MICO: minimally invasive cardiac output.
Demographics, time intervals relevant to intensive care and study admission, and baseline hemodynamics
At baseline, clinical signs of hypovolemia and clinically relevant hypotension were the most frequent criteria of hemodynamic instability, with no significant differences between the groups (Table ). The number of patients with at least three criteria of hemodynamic instability was higher in the MICO group (P = .05; Table ).
Presence of criteria for hemodynamic instability at baseline
There were no significant differences between the study groups in volumes or types of fluids received for hemodynamic support in the first six hrs (Table ). The MICO group received slightly more colloids than the control group after 6 hrs (P = .01) and for the whole 24 hrs (P = .01). There were no differences in the frequency or type of inotropic or vasopressor drugs given, but vasodilators were used more frequently in the control group (P = .02; Table ). A pulmonary artery catheter was inserted in 19% of the patients in the MICO group and in 26% in the control group (P = .11).
Hemodynamic support with fluids and vasoactive drugs
At six hours, 45 patients (22%) in the MICO group and 52 patients (28%) in the control group were hemodynamically stable (P
= .24). In each group, 19 patients (10%) became stable before 6 hrs and remained stable thereafter (see Additional file 1
/Table ); 34 patients in each group were stable at each time point (6 hrs and 24 hrs). The Kaplan-Meier curves for reaching hemodynamic stability (the time point after which none of the instability criteria were present or reappeared; see Additional file 1
/Figure ) for 6 hrs showed no difference between the groups (P
= .250). The presence of individual criteria of hemodynamic instability at baseline and mechanical ventilation at baseline were compared between stable and unstable patients at 6 hrs, and variables with differences with a P-v
alue less than .10 were included in logistic regression analysis. Only an acute symptomatic decrease in blood pressure at baseline (P
= .050) and increased blood lactate at baseline (P
= .002) were significant predictors of instability at six hours (for additional details, see Additional file 1
In the MICO group, stroke volume increased marginally [baseline: 65 mL (20 mL), 6 hrs: 65 mL (20 mL), 24 hrs: 69 mL (20 mL); P = .002] and stroke volume variation decreased slightly over time (baseline: 16% (12%); 6 hrs: 15% (10%); 24 hrs: 14% (10%): P = .05), whereas cardiac output did not change significantly (baseline: 5.9 (2.0) L/minute, 6 hrs: 5.9 (1.8) L/minute; 24 hrs: 6.1 (1.8) L/minute: P = .23].
Neither the ICU mortality nor the hospital mortality was significantly different between the groups (ICU mortality MICO 18%, control 12%, P = .122, relative risk = 1.497
95% confidence interval 0.925 to 2.42; hospital mortality MICO 26%, control 21%, P
= .34, risk = 1.209, 95% confidence interval .843 to 1.735). There were more deaths from randomization until 24 hrs after end of study monitoring in the MICO group (MICO n = 16 vs. control n = 4, P
= .011). All but one of these deaths (in the MICO group) occurred after withdrawal of treatment due to poor prognosis of the underlying condition (for details, see Additional file 1
The 24-hr Kaplan-Meier curves (Figure ) indicated that patients in the control group were more likely to reach hemodynamic stability (P = .033). After excluding the early deaths, the difference was not significant (P = .11). When stratified according to number of instability criteria at baseline (≥ 3 vs. < 3 criteria), the difference between MICO and control groups was not significant (P = .79 for ≥ 3 criteria; P = .12 for < 3 criteria).
Hemodynamic stability (P = 0.033) and cumulative occurrence of deaths within the first 24 hrs. MICO: minimally invasive cardiac output.
Differences between survivors and non-survivors were tested for study group, presence of each of the individual criteria of hemodynamic instability at baseline and 6 hrs, mechanical ventilation at baseline and 6 hrs, stability at 6 hrs and 24 hrs, and time to achieve hemodynamic stability. Those with a P-
value less than .10 were included in logistic regression analysis. Only oliguria (P
= .000) and increased lactate (P
= .01) at baseline were significant predictors of hospital mortality (for additional details, see Additional file 1
/Results and Additional file 1
Resource utilization was similar in the two groups. The TISS score for the first 24 hrs in the ICU was 32 (8) in the MICO group and 32 (9) in the control group (P = .79). The sum of TISS scores for the whole ICU stay was 172 (215) in the MICO group and 174 (194) in the control group (P = .93). The median length of stay in the ICU was 2.0 (1.2 to 4.6) days in the MICO group and 2.5 (1.1 to 5.0) days in the control group (P = .38). The duration from ICU admission to hospital discharge was 11.0 (5.6 to 18.3) days in the MICO group and 10.4 (5.3 to 18.6) days in the control group (P = .78). Twenty-three patients (11%) in the MICO group and 29 (16%) in the control group were later readmitted to the ICU (P = .30).