Table 2. Analysis of Primary and Secondary Outcomes and Adverse Events.
| Moderate hypothermia (n = 168) |
Normothermia (n = 166) |
Estimate (95% CI)a |
Adjusted OR (95% CI)b |
P valuec | |
|---|---|---|---|---|---|
| Primary outcome | |||||
| Mortality at 30 d, No. (%) | 71 (42) | 84 (51) | RD, −8.3 (−16.3 to −0.3) | 0.71 (0.45 to 1.13) | .15 |
| Secondary outcomes d | |||||
| Composite outcome of death, heart transplant, escalation to LVAD implantation, or stroke, No. (%) | |||||
| At 30 de | 88 (52) | 106 (64) | RD, −11.5 (−23.2 to 0.2) | 0.61 (0.39 to 0.96) | .03 |
| At 60 df | 98 (58) | 110 (66) | RD, −8.0 (−21.4 to 5.5) | 0.70 (0.44 to 1.11) | |
| At 180 dg | 102 (61) | 114 (69) | RD, −8.0 (−22.4 to 6.4) | 0.69 (0.43 to 1.11) | |
| Mortality, No. (%) | |||||
| At 48 h | 10 (6) | 11 (7) | RD, −0.7 (−5.3 to 3.9) | 0.98 (0.38 to 2.51) | |
| At 7 d | 29 (17) | 46 (28) | RD, −10.4 (−16.6 to −4.3) | 0.53 (0.31 to 0.93) | |
| At 60 d | 82 (49) | 91 (55) | RD, −6.0 (−16.7 to 4.6) | 0.79 (0.50 to 1.25) | |
| At 180 d | 88 (52) | 96 (58) | RD, −5.5 (−17.5 to 6.5) | 0.81 (0.51 to 1.29) | .38 |
| Venoarterial ECMO duration since randomization, mean (SD), d | 9.3 (9.0) | 8.1 (5.0) | MD, 1.2 (−0.2 to 2.7) | 1.11 (0.76 to 1.61) | |
| 7-d net intake of intravenous fluids, mean (SD), mL | 4042 (5036) | 3692 (5802) | MD, 295 (−409 to 999) | 1.19 (0.82 to 1.73) | |
| Length of use of vasopressors in the ICU, mean (SD), d | (n = 164) 8.4 (8.8) |
(n = 162) 7.2 (6.9) |
MD, 1.2 (−0.7 to 3.1) | 1.18 (0.80 to 1.72) | |
| Time to normalization of lactate level, mean (SD), dh | 2.4 (2.3) | 2.6 (2.4) | MD, −0.2 (−0.6 to 0.3) | 1.08 (0.70 to 1.66) | |
| No. of days alive without failure of organ or organs at 7 d, mean (SD)i | (n = 154) | (n = 156) | |||
| Defined as ≥1 component with a SOFA score >2 | 3.0 (2.5) | 2.5 (2.6) | MD, 0.5 (0 to 1.0) | 1.58 (1.05 to 2.38) | |
| Defined as ≥1 component with a SOFA score >3 | 5.2 (2.6) | 4.3 (2.8) | MD, 0.9 (0.4 to 1.3) | 2.03 (1.31 to 3.15) | |
| Ventilator-free days, mean (SD) | (n = 167) | (n = 165) | |||
| At 30 d | 9.1 (11.2) | 8.3 (11.2) | MD, 0.9 (−2.4 to 4.1) | 1.10 (0.72 to 1.69) | |
| At 60 d | 22.7 (25.1) | 20.8 (24.9) | MD, 1.9 (−4.2 to 7.9) | 1.12 (0.74 to 1.71) | |
| At 180 d | 77.7 (85.9)j | 67.7 (82.9)j | MD, 10.3 (−9.0 to 29.5) | 1.26 (0.83 to 1.93) | |
| Kidney replacement therapy–free days, mean (SD) | (n = 167) | (n = 165) | |||
| At 30 d | 15.2 (15.0) | 11.7 (14.5) | MD, 3.5 (0.6 to 6.5) | 1.55 (1.02 to 2.37) | |
| At 60 d | 29.2 (30.0) | 23.9 (28.4) | MD, 5.3 (−0.2 to 10.8) | 1.40 (0.92 to 2.13) | |
| At 180 d | 84.4 (91.6)j | 71.0 (86.7)j | MD, 13.6 (−5.1 to 32.3) | 1.46 (0.95 to 2.23) | |
| Length of stay, mean (SD), d | |||||
| In the ICU | 18.7 (20.3) | 17.8 (19.1) | MD, 0.9 (−4.0 to 5.7) | 1.16 (0.79 to 1.69) | |
| At the hospital | 32.3 (31.8) | 30.4 (34.0) | MD, 1.9 (−5.7 to 9.5) | 1.33 (0.91 to 1.94) | |
| Adverse events | |||||
| Occurred during venoarterial ECMO | |||||
| Moderate or severe bleeding, No. (%)k | 69 (41) | 70 (42) | RD, −1.0 (−10.1 to 8.1) | 0.94 (0.60 to 1.48) | |
| Received transfusion with only packed red blood cells | |||||
| No. (%) | 53 (32) | 50 (30) | RD, 1.3 (−6.5 to 9.1) | 1.10 (0.68 to 1.79) | |
| No. of units transfused, mean (SD) | 8.3 (9.0) | 5.4 (6.3) | MD, 3.2 (0.6 to 5.8) | 2.84 (1.37 to 5.86) | |
| Had ≥1 of the following 3 infection types, No. (%)l | 87 (52) | 86 (52) | RD, 0 (−12.3 to 12.2) | 0.97 (0.63 to 1.51) | |
| Pulmonary only | 74 (44) | 60 (36) | RD, 7.8 (−2.7 to 18.3) | 1.39 (0.89 to 2.18) | |
| Bacteremia only | 33 (20) | 50 (30) | RD, −10.5 (−22.4 to 1.4) | 0.55 (0.33 to 0.92) | |
| Venoarterial ECMO cannulae only | 14 (8) | 18 (11) | RD, −2.4 (−7.9 to 3.0) | 0.73 (0.35 to 1.54) | |
Abbreviations: ECMO, extracorporeal membrane oxygenation; LVAD, left ventricular assist device; ICU, intensive care unit; MD, mean difference; OR, odds ratio; RD, risk difference; SOFA, sequential organ failure assessment.
The RDs are expressed as percentages and were calculated using a binomial generalized estimating equation (GEE) model with identity link that accounted for intracenter correlation. The MDs were calculated using a gaussian GEE model with identity link that accounted for intracenter correlation.
The ORs were obtained from logistic regression models for binary end points or ordinal logistic regression models for continuous end points and were adjusted for age, prior myocardial infarction, prior cardiac arrest, after cardiac surgery, vasopressor dose, lactate level, and SOFA score at baseline. An OR greater than 1 indicates that the values are increased in the moderate hypothermia group compared with the normothermia group.
The secondary outcomes were analyzed using a hierarchical testing procedure that was implemented until the P value was nonsignificant; therefore, most of the P values were omitted.
Two secondary outcomes were not reported because they were redundant with other outcomes (durations of mechanical ventilation and kidney replacement therapy).
In the moderate hypothermia group, 71 patients died vs 84 in the normothermia group; 3 vs 7, respectively, for heart transplant; 18 vs 15 for escalation to LVAD implantation; and 11 vs 10 for stroke.
In the moderate hypothermia group, 82 patients died vs 91 in the normothermia group; 4 vs 7, respectively, for heart transplant; 20 vs 15 for escalation to LVAD implantation; and 12 vs 12 for stroke.
In the moderate hypothermia group, 88 patients died vs 96 in the normothermia group; 4 vs 8, respectively, for heart transplant; 20 vs 15 for escalation to LVAD implantation; and 12 vs 13 for stroke.
Defined as the first time the lactate level was in the normal range (<2.2 mmol/L measured on days 1-7). If a value was missing, and the previous value was not in the normal range, it was assumed that the patient had not achieved a normal lactate level. The value of 8 days was assigned to all patients who never had a normal level.
The SOFA score is for mortality prediction. The score is based on the degree of dysfunction of 6 organ systems and ranges from 0 to 24. The 4 components (respiratory, liver, coagulation, and kidney; each component scored from 0 to 4) were evaluated on days 1 to 7. Missing values for the 4 components were imputed using the last out carried forward (LOCF) method starting from baseline values (ie, if a value was missing at day 1, this value was replaced with the baseline value). All patients alive on day 1 who had a missing value for at least 1 of the 4 components at day 1 (after the LOCF imputation) were excluded from this analysis. The time alive without organ failure at day 7 was defined as the difference between the number of days alive with organ failure between days 1 and 7 and the number of days alive between days 1 and 7. The value of 0 days was assigned to all patients who died before day 1.
For 180 days, the sample size is the whole sample (168 for moderate hypothermia and 166 for normothermia).
Moderate bleeding was defined as requiring blood transfusion but not resulting in hemodynamic compromise requiring treatment. Severe bleeding was defined as intracerebral or resulting in substantial hemodynamic compromise.
Identified by the clinicians in charge of the patients and selected based on the work of Schmidt et al.18