Recombinant Activated Factor VII in Aortic Surgery for Patients Under Hypothermic Circulatory Arrest

Figures & data

Table 1 Baseline and Operative Characteristics

Characteristic	Before Matching				After Matching
	rFVIIa (n=42)	Non-rFVIIa (n=102)	p-value	SMD	rFVIIa (n=29)	Non-rFVIIa (n=29)	p-value	SMD
Age (y)	76.5 (69.5, 82.3)	73.5 (66.0, 79.0)	0.065	0.150	75.0 (65.0, 81.0)	78.0 (68.5, 80.5)	0.820	0.192
Sex (Male)	24 (57.1%)	57 (55.9%)	1.000	0.025	17 (58.6%)	18 (62.1%)	1.000	0.071
Body mass index (kg/m^2)	23.1 (19.8, 26.8)	22.8 (20.8, 26.3)	0.610	0.180	23.1 (20.4, 27.3)	21.5 (20.0, 24.7)	0.370	0.237
AAD/TAA	27 (64.3%)/15 (35.7%)	53 (52.0%)/49 (48.0%)	0.200	0.252	16 (55.2%)/13 (44.8%)	16 (55.2%)/13 (44.8%)	1.000	<0.001
Emergency surgery	27 (64.3%)	51 (50.0%)	0.142	0.292	16 (55.2%)	17 (58.6%)	1.000	0.07
Malperfusion	5 (11.9%)	9 (8.8%)	0.550	0.101	3 (10.3%)	2 (6.9%)	1.000	0.123
Shock (requiring hemodynamic support)	6 (14.3%)	3 (2.9%)	0.019	0.413	3 (10.3%)	2 (6.9%)	1.000	0.123
Cardiac tamponade	8 (19.0%)	8 (7.8%)	0.077	0.333	5 (17.2%)	6 (20.7%)	1.000	0.088
GCS <8	1 (2.4%)	3 (2.9%)	1.000	0.035	1 (3.4%)	2 (6.9%)	1.000	0.156
Smoking	7 (16.7%)	27 (26.5%)	0.281	0.240	5 (17.2%)	5 (17.2%)	1.000	<0.001
Hypertension	33 (78.6%)	78 (76.5%)	0.831	0.050	24 (82.8%)	24 (82.8%)	1.000	<0.001
Diabetes mellitus	7 (16.7%)	12 (11.8%)	0.428	0.141	5 (17.2%)	6 (20.7%)	1.000	0.088
Liver dysfunction	6 (14.3%)	8 (7.8%)	0.234	0.206	3 (10.3%)	4 (13.8%)	1.000	0.106
Anticoagulant treatment	5 (11.9%)	10 (9.8%)	0.766	0.068	2 (6.9%)	3 (10.3%)	1.000	0.123
Antiplatelet treatment	7 (16.7%)	17 (16.7%)	1.000	<0.001	6 (20.7%)	7 (24.1%)	1.000	0.083
JapanSCORE II 30-day mortality (%)	8.4 (5.6, 14.0)	6.1 (3.9, 10.2)	0.033	0.355	6.9 (4.3, 11.1)	7.1 (4.4, 13.5)	0.665	0.088
Hemoglobin (g/dl)	11.5 (10.0, 13.6)	12.5 (10.8, 14.0)	0.092	0.285	11.9 (10.0, 13.7)	11.7 (10.2, 13.6)	0.811	0.101
Platelet count (10^9/L)	157 (124, 188)	177 (142, 213)	0.015	0.401	158 (126, 179)	168 (130, 188)	0.787	0.074
APTT (s)	31.2 (27.4, 37.7)	28.4 (26.2, 31.9)	0.005	0.284	31.1 (27.5, 35.2)	30.3 (27.2, 34.8)	0.795	0.190
PT-INR	1.07 (1.00, 1.24)	1.02 (0.96, 1.10)	0.006	0.314	1.05 (0.98, 1.18)	1.06 (1.00, 1.14)	0.964	0.056
Fibrinogen (g/L)	2.43 (1.62, 2.96)	2.90 (2.46, 3.91)	<0.001	0.668	2.64 (1.77, 3.29)	2.45 (2.21, 2.97)	0.922	0.053
Serum creatinine (mg/dl)	0.94 (0.72, 1.11)	0.87 (0.70, 1.10)	0.427	0.149	0.94 (0.75, 1.12)	1.00 (0.78, 1.25)	0.160	0.195
Surgery
Primary procedure			0.146	0.274			1.000	<0.001
Total arch replacement	19 (45.%2)	60 (58.8%)			14 (48.3%)	14 (48.3%)
Hemiarch replacement	23 (54.8%)	42 (41.2%)			15 (51.7%)	15 (51.7%)
Concomitant procedure	14 (33.3%)	26 (25.5%)	0.413	0.173	9 (31.0%)	8 (27.6%)	1.000	0.076
None	28 (66.7%)	76 (74.5%)			20 (69.0%)	21 (72.4%)
AVR or AVP	3 (7.1%)	4 (3.9%)			2 (6.9%)	2 (6.9%)
Bentall	2 (4.8%)	1 (1.0%)			1 (3.4%)	0 (0%)
David	3 (7.1%)	7 (6.9%)			2 (6.9%)	3 (10.3%)
CABG	7 (16.7%)	11 (10.8%)			4 (13.8%)	3 (10.3%)
Others	0 (0%)	3 (2.9%)			0 (0%)	0 (0%)
CPB time (min)	169 (145, 230)	169 (142, 192)	0.136	0.437	161 (136, 227)	177 (136, 216)	0.754	0.084
ACC time (min)	110 (88, 146)	97 (79, 121)	0.049	0.376	102 (80, 141)	110 (75, 123)	0.462	0.119
Lowest rectal temperature (°C)	27.5 (25.7, 27.9)	26.1 (25.3, 27.6)	0.043	0.421	27.4 (25.6, 27.9)	26.6 (25.4, 27.8)	0.546	0.183
HCA time (min)	40 (28, 49)	39.5 (29.0, 53.0)	0.986	0.094	40 (28, 50)	36 (25, 56)	0.829	0.039

Notes: The number of “concomitant procedures” means the number of patients who added some sort of adjunct procedure including AVR, AVP, Bentall, David, CABG, and others. Abbreviations: AAD, acute aortic dissection; ACC, aortic cross clamp; APTT, activated partial thromboplastin time; AVP, aortic valvuloplasty; AVR, aortic valve replacement; CABG, coronary artery bypass grafting; CPB, cardiopulmonary bypass; GCS, Glasgow coma scale; HCA, hypothermic circulatory arrest; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII; SMD, standardized mean difference; and TAA, thoracic aortic aneurysm.

Table 2 Perioperative Bleeding and Blood Products in the Entire Unmatched and Propensity-Score Matched Populations

Characteristic	Before Matching			After Matching
	rFVIIa (n = 42)	Non-rFVIIa (n = 102)	p-value	rFVIIa (n = 29)	Non-rFVIIa (n = 29)	p-value
Bleeding volume intra-OP (mL)	6492 (3643, 11,502)	3652 (2425, 5207)	<0.001	6773 (4019, 10,185)	3639 (2399, 6627)	0.012
PRBC intra-OP (unit)	30 (20, 37)	20 (12, 24)	<0.001	26 (19, 34)	20 (12, 24)	0.048
FFP intra-OP (unit)	36 (24, 47)	22 (16, 30)	<0.001	34 (20, 46)	24 (18, 32)	0.021
PC intra-OP (unit)	50 (40, 60)	40 (40, 60)	0.099	55 (40, 60)	40 (40, 60)	0.472
Cryoprecipitate intra-OP (unit)	12 (12, 24)	12 (12, 12)	0.002	12 (12, 24)	12 (12, 12)	0.405
rFVIIa (µg/kg)	56 (35, 85)	-		56 (32, 83)	-
Fibrinogen concentrate (g)	3 (0, 3)	0 (0, 0)	<0.001	3 (0, 3)	0 (0, 0)	<0.001
Bleeding volume until 12 h (mL)	1099 (598, 1425)	655 (469, 1098)	0.005	790 (490, 1470)	740 (540, 1233)	0.071
PRBC until 12 h (unit)	3 (0, 6)	2 (0, 5)	0.082	2 (0, 6)	2 (0, 5)	0.370
FFP until 12 h (unit)	7 (4, 10)	4 (4, 8)	0.040	6 (4, 9)	6 (4, 8)	0.576
PC until 12 h (unit)	0 (0, 20)	0 (0, 0)	0.005	0 (0, 20)	0 (0, 10)	0.967

Abbreviations: FFP, fresh frozen plasma; OP, operation; PC, platelet concentrates; PRBC, packed red blood cells; rFVIIa, recombinant activated factor VII.

Table 3 Postoperative Data and Complications in the Entire Unmatched and Propensity-Score Matched Populations

	Before Matching			After Matching
	rFVIIa (n = 42)	Non-rFVIIa (n = 102)	p-value	rFVIIa (n = 29)	Non-rFVIIa (n = 29)	p-value
Laboratory data after surgery
Hb (g/dl)	10.6 (9.3, 11.6)	10.3 (9.6, 12.0)	0.476	10.6 (9.0, 11.5)	10.5 (9.5, 11.8)	0.381
Plt (10^9 /L)	97 (74, 133)	138 (106, 167)	<0.001	97 (73, 137)	142 (106, 169)	<0.001
APTT (s)	46.6 (33.4, 56.3)	38.5 (35.0, 47.3)	0.017	45.2 (33.6, 55.1)	37.1 (33.4, 44.0)	0.206
PT-INR	0.84 (0.80, 1.01)	1.15 (1.10, 1.24)	<0.001	0.86 (0.81, 1.03)	1.13 (1.08, 1.18)	<0.001
Fibrinogen (g/L)	2.15 (1.85, 2.85)	2.26 (1.97, 2.67)	0.021	2.10 (1.79, 2.59)	2.39 (2.06, 2.69)	0.846
Serum creatinine* (mg/dl)	1.21 (0.89, 1.73)	1.31 (1.07, 1.74)	0.604	1.21 (0.94, 1.72)	1.10 (0.83, 1.63)	0.226
Intubation time (h)	17 (10, 53)	16 (11, 51)	0.046	25 (12, 96)	16 (10, 42)	0.991
Deep sternal wound infection	1 (2.4%)	1 (1.0%)	0.500	1 (3.4%)	0 (0%)	1.000
Septicemia	2 (4.8%)	3 (2.9%)	0.629	0 (0%)	1 (3.4%)	1.000
Renal failure**	5 (11.9%)	11 (10.8%)	1.000	1 (3.4%)	3 (10.3%)	0.500
Paraparesis	2 (4.8%)	3 (2.9%)	0.629	1 (3.4%)	1 (3.4%)	1.000
Deep venous thrombosis	0 (0%)	2 (2.0%)	1.000	0 (0%)	1 (3.4%)	1.000
Pulmonary embolism	0 (0%)	0 (0%)		0 (0%)	0 (0%)
Myocardial infarction	0 (0%)	0 (0%)		0 (0%)	0 (0%)
Stroke	3 (7.1%)	5 (4.9%)	0.692	1 (3.4%)	1 (3.4%)	1.000
Minor stroke	2 (4.8%)	1 (1.0%)	0.204	1 (3.4%)	0 (0%)	1.000
Disabling stroke	1 (2.4%)	4 (3.9%)	1.000	0 (0%)	1 (3.4%)	1.000
Cardiac tamponade	1 (2.4%)	3 (2.9%)	1.000	0 (0%)	1 (3.4%)	1.000
Re-exploration	4 (9.5%)	4 (3.9%)	0.231	4 (13.8%)	3 (10.3%)	1.000
30-day mortality	3 (7.1%)	2 (2.0%)	0.148	1 (3.4%)	1 (3.4%)	1.000

Notes: *Peak postoperative, **Serum creatinine > 2.0 mg/dl and more than twice before surgery, or requiring newly hemodialysis.

Abbreviations: APTT, activated partial thromboplastin time; Plt, platelet; PT-INR, prothrombin time international normalized ratio; rFVIIa, recombinant activated factor VII.

Table 4 Comparison Between Acute Aortic Dissection and Thoracic Aortic Aneurysm Regarding the Detected Risk Factors for rFVIIa Use and Outcomes

Characteristic	AAD (n=80)	TAA (n=64)	p-value
Use of rFVIIa	27 (12.5%)	15 (23.4%)	0.176
Age (y)	75.0 (66.5, 82.0)	71.5 (66.0, 78.0)	0.070
Sex (Male)	35 (43.7%)	46 (71.9%)	0.001
Shock (requiring hemodynamic support)	9 (11.3%)	0 (0%)	0.005
JapanSCORE II 30-day mortality rate	8.30(5.85, 13.2)	4.60 (2.70, 8.45)	<0.001
Platelet count (10^9/L)	157 (129, 190)	184 (158, 246)	<0.001
APTT (s)	31 (27, 37)	28 (26, 31)	0.022
PT-INR	1.08 (1.01, 1.21)	0.99 (0.93, 1.04)	<0.001
Fibrinogen (g/L)	253(177, 374)	291 (256, 393)	0.022
Aortic clamp time (min)	100 (77, 122)	103 (81, 122)	0.532
Lowest rectal temperature (°C)	26.5 (25.5, 27.7)	26.3 (25.4, 27.9)	0.915
Re-exploration	5 (6.3%)	3 (4.7%)	0.684
Stroke	5 (6.3%)	3 (4.7%)	0.684
30-day Mortality	4 (5.0%)	1 (1.6%)	0.382

Abbreviations: rFVIIa, recombinant activated factor VII; APTT, activated partial thromboplastin time; PT-INR, prothrombin time international normalized ratio.