ORIGINAL ARTICLE
European Journal of Cardio-Thoracic Surgery 48 (2015) 301–307 doi:10.1093/ejcts/ezu412 Advance Access publication 28 October 2014
Cite this article as: Gertler R, Hapfelmeier A, Tassani-Prell P, Wiesner G, Martin K. The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery. Eur J Cardiothorac Surg 2015;48:301–7.
The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery Ralph Gertlera,*, Alexander Hapfelmeierb, Peter Tassani-Prella, Gunther Wiesnera and Klaus Martina a b
Institute of Anesthesiology, German Heart Center, Technische Universität, München, Munich, Germany Institute of Medical Statistics and Epidemiology, Klinikum Rechts der Isar, Technische Universität, München, Munich, Germany
*Corresponding author. Lazarettstr. 36, 80636 Munich, Germany. Tel: +49-89-12184636; fax +49-89-12184613; e-mail: [email protected] (R. Gertler). Received 21 July 2014; received in revised form 25 September 2014; accepted 3 October 2014
Abstract OBJECTIVES: Platelet dysfunction is one of the major haematological disturbances of cardiopulmonary bypass (CPB). In addition, cyanosis is known to cause further coagulation disturbances. METHODS: We prospectively studied 110 children under 1 year of age for the effects of cyanosis on baseline platelet aggregation, the time course of function on cardiopulmonary bypass, the effect on chest tube drainage (CTD) and the transfusion requirements. Using multiple electrode aggregometry (MULTIPLATE™) with the activators adenosine diphosphate (ADP) and thrombin-related activation peptide (TRAP), platelet aggregation was assessed and examined for predictive value. RESULTS: Neonates under 30 days of age (n = 51) and infants (n = 59) were separated for analysis. Cyanosis had no significant effect on platelet function during the first 24 h after surgery. Similarly, there was no association to perioperative platelet function, CTD or exposures to blood products. ADP after protamine correlated significantly with the total number of exposures for neonates and infants and CTD at 6 h in the newborn group. Upon intensive care unit admission, ADP values correlated to the total number of exposures to blood products. No other platelet function value was able to clinically predict CTD or subsequent blood transfusion requirements.
Keywords: Coagulation • Paediatric cardiac anaesthesia • Blood platelets
INTRODUCTION Abnormal platelet function is one of the haematological features observed in congenital heart disease (CHD). Mauer [1] was one of the first to describe this impairment in platelet function in severely cyanotic children. He described a defect in the release of adenosine diphosphate (ADP) from platelets with normal amounts of ADP in the granula [1]. The main underlying mechanism hereby seems to be the longstanding effect of hypoxia and erythrocytosis. The surgical correction of CHD in infants under 1 year necessitates the transfusion of multiple blood products. This requirement is due to the extremes of haemodilution, temperature and complexity of surgery involving multiple suture lines along major vessels. Besides heparin management, platelet dysfunction has been considered a major culprit in postoperative bleeding during congenital cardiac surgery. Both platelet function and the coagulation system undergo maturational changes that may have a major
effect on blood loss and transfusion requirements. Two smaller studies have previously examined the relationship between platelet function and postoperative bleeding in paediatric patients and found no association [2, 3]. Following these earlier studies, we present our data on a group of neonates and infants, focusing on the effects of cyanosis on platelet aggregation. The primary endpoint was the association between baseline platelet aggregation and cyanosis in neonates and infants with congenital heart disease (CHD) as measured by multiple electrode aggregometry (MEA, MULTIPLATE™, Verum Diagnostica, Munich, Germany). Neonatal platelets are influenced by maturational changes while infantile platelets are altered by chronic activation and exhaustion. Our secondary end-points were whether platelet aggregation is different between these two groups during the perioperative course of the first 24 h and has any relation to postoperative blood losses. Postoperative blood losses were quantified by chest tube drainage (CTD), and the necessity for blood transfusion was
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
CONGENITAL
CONCLUSIONS: In our study population, we observed no clinically significant effect of cyanosis on baseline and the perioperative course of platelet function, CTD and the number of exposures to blood products. Therefore, children under 1 year of age do not require a different approach with regard to platelet transfusions, independent of cyanosis. Clinically, platelet function was not a reliable predictor of CTD or blood transfusion requirements.
302
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
measured by the total number of exposures to blood products. We also attempted to define the predictive value of perioperative MULTIPLATE™ measurements on blood loss and transfusion requirements.
METHODS The study was approved by the ethics committee of the Medical Faculty, Technische Universität München, Germany (reference number 2211/08). Written parental consent was obtained in all cases. We included 110 children under 1 year of age, undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB). Cyanosis was defined as SpO2 25% during CPB and >35% in patients with a
residual cyanosis. An INR >1.2 was corrected with additional FFP. Blood loss at 6 and 24 h postoperatively and the amount of allogeneic blood products used intra- and postoperatively were recorded. Blood samples were obtained from an arterial catheter after the induction of anaesthesia and insertion (Baseline BL), 10 min after protamine administration (Prot), upon arrival in the ICU (ICU) and on the morning of postoperative day 1 (POD 1). For the MULTIPLATE™ (Dynabyte Medical, Munich, Germany) measurements, blood was drawn into 2-ml hirudin prefilled tubes (25 µg/ml) and rested for 30 min at room temperature before analysis as recommended by the manufacturer (time window 30–240 min). We performed testing using adenosine diphosphate (ADP Test 0.2 mM, Instrumentation Laboratory, Munich, Germany) and thrombin-related activation peptide (TRAP)-activating agents (TRAP test 1 mM, Instrumentation Laboratory). Technical details can be found elsewhere. Results are presented as area under the curve and the anaesthesiologist at the bedside was blinded to the results. Platelet counts and routine laboratory parameters [haemoglobin (Hb), INR, PTT, fibrinogen] were measured at the according time points.
STATISTICS Descriptive and explorative statistics were used for data analysis. The distribution of qualitative measures is presented by absolute and relative frequencies. Depending on the cell counts of corresponding contingency tables, group comparisons were performed by χ 2 tests or Fisher’s exact tests. Mean ± SD and median (interquartile range) are given for normally and non-normally distributed data, respectively. Accordingly, group comparisons were performed by t-tests and Mann–Whitney U-tests. The relation of quantitative measures was assessed by Spearman’s correlation coefficient. All statistical testing was performed on an explorative significance level of 0.05. Analysis was conducted using PASW Statistics for Windows Version 21.0 (IBM Corporation, Somer, NY, USA).
RESULTS Table 1 summarizes the demographic and surgical data. The severity of surgical intervention was comparable. No significant
Table 1: Demographics and surgical characteristics Neonates (n = 51) Demographics Patient characteristics Age (days) Weight (g) Height (cm) Male gender (%) PGE2 (%) Surgical characteristics Basic Aristotle score RACHS-1 score CPB time (min) DHCA (%)
Infants (n = 59)
Acyanotic (n = 20)
Cyanotic (n = 31)
Acyanotic (n = 40)
Cyanotic (n = 19)
9 (6–13) 3.2 ± 0.5 51 ± 4 10 (50%) 11 (55%)
12 (7–14) 3.3 ± 0.5 51 ± 3 17 (55%) 26 (84%)*
137 (106–179) 5.5 ± 1.4 62 ± 7 18 (45%) 2 (5%)
147 (106–192) 5.7 ± 1.5 61 ± 6 11 (58%) 2 (11%)
10.2 (10–11) 4 (4–6) 132 (106–169) 12 (60%)
10.8 (6.8–14.5) 4 (3–6) 95 (70–41)* 17 (55%)
6 (6–9) 2 (2–3) 85 (58–101) 3 (8%)
7.5 (7–8) 2 (2–3) 78 (52–93) 1 (5%)
Data are presented as median (interquartile range 25–75%) or absolute frequency (percentage). *P < 0.05 cyanotic versus acyanotic within age group. CPB: cardiopulmonary bypass; PGE2: prostaglandin E2; RACHS-1: risk-adjusted congenital heart surgery core; DHCA: deep hypothermic circulatory arrest.
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
differences between the two neonatal groups were observed except for shorter bypass and aortic cross-clamp times in cyanotic neonates. In the infant group, only 37% of cyanotic children required aortic clamping compared with 100% in the acyanotic group. There was a weak correlation of haemoglobin on baseline platelet function [Spearman Rho for Hb vs ADP (R = −0.401*, P = .025) and TRAP (R = −0.368*, P = 0.046)]. Cyanosis did not have any statistically significant effect on platelet function (Table 2).
303
However, in the infant group, baseline TRAP values for the acyanotic infant groups were lower than in the cyanotic infant [83 (64– 96) U vs 95 (79–101) U], though not statistically significant (P = 0.075). During the time on CPB, in vitro platelet function decreased significantly and recovered only partially by the end of Day 1 without any detectable influence of cyanosis. As for the laboratory values (Table 3), cyanotic infants had significantly higher baseline values of haemoglobin (P = 0.002) and fibrinogen
Table 2: Course of ADP and TRAP values Neonates (n = 51)
ADP (AU [U]) Baseline After protamine ICU arrival POD 1 TRAP (AU [U]) Baseline After protamine ICU arrival POD 1
Infants (n = 59)
Acyanotic (n = 20)
Cyanotic (n = 31)
P-value
Acyanotic (n = 40)
Cyanotic (n = 19)
P-value
86 (42–98) 16 (8–20)* 21 (11–37)* 57 (39–86)*
91 (77–101) 11 (6–20) * 18 (13–29)* 64 (33–93)*
0.306 0.411 0.586 0.864
68 (49–79) 15 (10–20)* 20 (11–28)* 45 (32–65)*
76 (63–85) 15 (10–23)* 16 (10–26)* 53 (34–64)*
0.178 0.715 0.521 0.823
96 (78–112) 23 (11–33)* 41 (22–71)* 77 (62–87)*
99 (88–109) 13 (8–22)* 34 (21–59)* 74 (77–98)*
0.721 0.222 0.405 0.846
83 (64–96) 25 (15–39)* 34 (25–54)* 56 (50–80)*
95 (79–101) 32 (21–43)* 37 (19–48)* 69 (60–84)*
0.075 0.166 0.846 0.226
Data are presented as median (interquartile range 25–75%) and P-values are within age groups. *P < 0.05 versus baseline. ADP: adenosine diphosphate; TRAP: thrombin receptor-activating peptide; AU [U]: area under curve; POD 1: postoperative day 1.
Table 3: Coagulation profile
Haemoglobin (g/dl) Baseline After protamine ICU arrival POD 1 Platelet count (103/µl) Baseline After protamine ICU arrival POD 1 INR Baseline After protamine ICU arrival POD 1 PTT (s) Baseline After protamine ICU arrival POD 1 Fibrinogen (mg/dl) Baseline After protamine ICU arrival POD 1
Infants
Acyanotic
Cyanotic
P-value
Acyanotic
Cyanotic
P-value
13.5 ± 2.2 12.4 ± 1.5 14.1 ± 3.2 15.4 ± 2.2*
13.2 ± 2.3 12.5 ± 2.0 14.5 ± 1.9* 15.2 ± 1.8*
0.609 0.760 0.494 0.966
11.7 ± 1.6 11.5 ± 1.6 12.9 ± 1.5* 13.9 ± 2.3*
13.3 ± 1.4 11.6 ± 1.3* 13.7 ± 1.9 14.2 ± 2.2
0.002 0.897 0.153 0.667
309 (262–358) 84 (56–126)* 146 (86–190)* 152 (106–207)*
303 (230–478) 81 (57–131)* 135 (80–178)* 141 (108–230)*
0.630 1.0 0.642 0.975
307 (261–387) 100 (84–133)* 117 (91–149)* 128 (89–176)*
343 (274–415) 110 (90–142)* 99 (78–135)* 134 (123–169)*
0.215 0.596 0.377 0.385
1.3 (1.1–1.4) 1.4 (1.4–1.9)* 1.2 (1.1–1.4) 1.2 (1.1–1.3)
1.1 (1.0–1.3) 1.6 (1.4–1.8)* 1.2 (1.1–1.3) 1.1 (1.0–1.2)
0.041 0.384 0.391 0.271
1.1 (1.0–1.1) 1.5 (1.3–1.6)* 1.2 (1.1–1.2)* 1.1 (1.1–1.2)*
1.1 (1.0–1.1) 1.4 (1.3–1.8)* 1.1 (1.1–1.2) 1.1 (1.1–1.2)
0.946 0.750 0.141 0.650
45 (40–54) 80 (54–150)* 54 (42–84) 48 (41–59)
46 (35–56) 67 (51–126)* 47 (41–60) 46 (37–65)
0.435 0.440 0.367 0.533
39 (35–43) 55 (48–66)* 45 (40–50)* 43 (38–51)*
39 (32–52) 59 (45–77)* 42 (38–51) 41 (36–66)
0.727 0.655 0.441 0.804
0.082 0.324 0.422 0.852
269 ± 116 181 ± 54* 200 ± 43* 304 ± 68
221 ± 90 162 ± 48* 202 ± 76 263 ± 64*
280 ± 111 180 ± 60* 228 ± 66 273 ± 61
324 ± 131 194 ± 57* 221 ± 53* 315 ± 82
0.018 0.365 0.200 0.436
Data are presented as mean ± SD and compared by t-test or median (interquartile range 25–75%) and compared by Mann–Whitney U-test, depending on the distribution. P-values are within age groups. *P < 0.05 versus baseline. ICU: intensive care unit; POD 1: postoperative day 1; INR: international normalized ratio; PTT: partial thromboplastin time.
CONGENITAL
Neonates
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
304
Table 4: Transfusion data and cumulative chest tube drainage Neonates (n = 51) n
Acyanotic (n = 20)
PRBC 1 14 2 1 ≥3 5 FFP 1 5 2 9 ≥3 6 Platelets 0 6 1 9 ≥2 5 Total exposures 2 2 3 6 4 5 ≥5 7 Cumulative CTD (ml/kg) 6h 17 (13–34) 24 h 41 (25–62)
Infants (n = 59) χ2
Acyanotic (n = 40)
Cyanotic (n = 19)
χ2
0.008
34 6 0
16 2 1
0.389
0.150
15 23 2
2 14 3
0.062
0.305
36 4 0
19 0 0
0.295
2 6 7 16
0.670
15 18 3 4
1 13 3 2
0.067
23 (13–37) 44 (27–53)
0.637 0.719
10 (7–13) 19 (15–26)
8 (4–13) 15 (9–28)
0.251 0.355
Cyanotic (n = 31)
10 13 8 2 15 14 16 9 6
Data are presented as absolute number of patients (n) and compared within groups by χ 2 test or Fisher’s exact test where indicated. CTD is shown as median (interquartile range 25–75%) and analysed by Mann–Whitney U-test. PRBC: packed red blood cells; FFP: fresh frozen plasma; CTD: chest tube drainage.
(P = 0.018). The coagulation profile was not statistically significantly different among acyanotic and cyanotic groups except for a higher INR at baseline in the cyanotic neonatal group. Transfusion requirements expressed as total number of exposures were similar within groups except for a statistically significant higher transfusion rate of PRBCs in the cyanotic newborn group (Table 4). Postoperative chest tube losses and the number of donor exposures were not statistically different within groups and not associated to platelet function or cyanosis. Overall baseline platelet function was a weak predictor of postoperative blood loss (Table 5). In neonates, ADP after protamine was related to CTD at 6 h after surgery and total blood product exposure in the first 24 h after ICU admission. In the same group, TRAP activity was weakly related to blood component exposure. For the infant group, ADP at the time of protamine infusion and upon ICU arrival correlated significantly with total blood exposure while TRAP was not significantly related to CTD and transfusion requirements.
Table 5: Spearman correlation coefficients and significance for platelet function vs blood loss and transfusion requirements
Neonates ADP baseline ADP after protamine ADP ICU admission TRAP baseline TRAP after protamine TRAP ICU admission
DISCUSSION We tested the association of cyanosis to baseline platelet aggregation during paediatric cardiac surgery and the time course of platelet function using the MULTIPLATE™ assay. The baseline platelet function was not significantly different in neonates and infants with or without cyanosis, and was a weak predictor of clinical blood transfusion requirements and postoperative CTD in cardiac surgery for children under 1 year of age.
Infants ADP baseline ADP after protamine ADP ICU admission TRAP baseline TRAP after protamine TRAP ICU admission
Platelet function and testing in neonates Platelet function of neonates is different from adults. Adhesion receptors are present early in foetal life, but become only fully
6h CTD
24 h CTD
Total exposures
r P-value r P-value r P-value r P-value r P-value r P-value
0.061 0.679 −0.301 0.037 −0.055 0.712 0.175 0.234 −0.236 0.107 −0.146 0.317
0.160 0.271 −0.141 0.340 0.073 0.622 0.208 0.156 −0.111 0.452 −0.052 0.723
−0.174 0.221 −0.323 0.024 −0.147 0.313 −0.020 0.893 −0.255 0.077 0.043 0.766
r P-value r P-value r P-value r P-value r P-value r P-value
−0.130 0.326 −0.204 0.121 −0.129 0.329 −0.152 0.254 −0.084 0.531 −0.106 0.425
−0.175 0.184 −0.251 0.055 −0.172 0.193 −0.218 0.100 −0.098 0.462 −0.135 0.309
−0.091 0.493 −0.442
European Journal of Cardio-Thoracic Surgery 48 (2015) 301–307 doi:10.1093/ejcts/ezu412 Advance Access publication 28 October 2014
Cite this article as: Gertler R, Hapfelmeier A, Tassani-Prell P, Wiesner G, Martin K. The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery. Eur J Cardiothorac Surg 2015;48:301–7.
The effect of cyanosis on perioperative platelet function as measured by multiple electrode aggregometry and postoperative blood loss in neonates and infants undergoing cardiac surgery Ralph Gertlera,*, Alexander Hapfelmeierb, Peter Tassani-Prella, Gunther Wiesnera and Klaus Martina a b
Institute of Anesthesiology, German Heart Center, Technische Universität, München, Munich, Germany Institute of Medical Statistics and Epidemiology, Klinikum Rechts der Isar, Technische Universität, München, Munich, Germany
*Corresponding author. Lazarettstr. 36, 80636 Munich, Germany. Tel: +49-89-12184636; fax +49-89-12184613; e-mail: [email protected] (R. Gertler). Received 21 July 2014; received in revised form 25 September 2014; accepted 3 October 2014
Abstract OBJECTIVES: Platelet dysfunction is one of the major haematological disturbances of cardiopulmonary bypass (CPB). In addition, cyanosis is known to cause further coagulation disturbances. METHODS: We prospectively studied 110 children under 1 year of age for the effects of cyanosis on baseline platelet aggregation, the time course of function on cardiopulmonary bypass, the effect on chest tube drainage (CTD) and the transfusion requirements. Using multiple electrode aggregometry (MULTIPLATE™) with the activators adenosine diphosphate (ADP) and thrombin-related activation peptide (TRAP), platelet aggregation was assessed and examined for predictive value. RESULTS: Neonates under 30 days of age (n = 51) and infants (n = 59) were separated for analysis. Cyanosis had no significant effect on platelet function during the first 24 h after surgery. Similarly, there was no association to perioperative platelet function, CTD or exposures to blood products. ADP after protamine correlated significantly with the total number of exposures for neonates and infants and CTD at 6 h in the newborn group. Upon intensive care unit admission, ADP values correlated to the total number of exposures to blood products. No other platelet function value was able to clinically predict CTD or subsequent blood transfusion requirements.
Keywords: Coagulation • Paediatric cardiac anaesthesia • Blood platelets
INTRODUCTION Abnormal platelet function is one of the haematological features observed in congenital heart disease (CHD). Mauer [1] was one of the first to describe this impairment in platelet function in severely cyanotic children. He described a defect in the release of adenosine diphosphate (ADP) from platelets with normal amounts of ADP in the granula [1]. The main underlying mechanism hereby seems to be the longstanding effect of hypoxia and erythrocytosis. The surgical correction of CHD in infants under 1 year necessitates the transfusion of multiple blood products. This requirement is due to the extremes of haemodilution, temperature and complexity of surgery involving multiple suture lines along major vessels. Besides heparin management, platelet dysfunction has been considered a major culprit in postoperative bleeding during congenital cardiac surgery. Both platelet function and the coagulation system undergo maturational changes that may have a major
effect on blood loss and transfusion requirements. Two smaller studies have previously examined the relationship between platelet function and postoperative bleeding in paediatric patients and found no association [2, 3]. Following these earlier studies, we present our data on a group of neonates and infants, focusing on the effects of cyanosis on platelet aggregation. The primary endpoint was the association between baseline platelet aggregation and cyanosis in neonates and infants with congenital heart disease (CHD) as measured by multiple electrode aggregometry (MEA, MULTIPLATE™, Verum Diagnostica, Munich, Germany). Neonatal platelets are influenced by maturational changes while infantile platelets are altered by chronic activation and exhaustion. Our secondary end-points were whether platelet aggregation is different between these two groups during the perioperative course of the first 24 h and has any relation to postoperative blood losses. Postoperative blood losses were quantified by chest tube drainage (CTD), and the necessity for blood transfusion was
© The Author 2014. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.
CONGENITAL
CONCLUSIONS: In our study population, we observed no clinically significant effect of cyanosis on baseline and the perioperative course of platelet function, CTD and the number of exposures to blood products. Therefore, children under 1 year of age do not require a different approach with regard to platelet transfusions, independent of cyanosis. Clinically, platelet function was not a reliable predictor of CTD or blood transfusion requirements.
302
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
measured by the total number of exposures to blood products. We also attempted to define the predictive value of perioperative MULTIPLATE™ measurements on blood loss and transfusion requirements.
METHODS The study was approved by the ethics committee of the Medical Faculty, Technische Universität München, Germany (reference number 2211/08). Written parental consent was obtained in all cases. We included 110 children under 1 year of age, undergoing cardiac surgery with the use of cardiopulmonary bypass (CPB). Cyanosis was defined as SpO2 25% during CPB and >35% in patients with a
residual cyanosis. An INR >1.2 was corrected with additional FFP. Blood loss at 6 and 24 h postoperatively and the amount of allogeneic blood products used intra- and postoperatively were recorded. Blood samples were obtained from an arterial catheter after the induction of anaesthesia and insertion (Baseline BL), 10 min after protamine administration (Prot), upon arrival in the ICU (ICU) and on the morning of postoperative day 1 (POD 1). For the MULTIPLATE™ (Dynabyte Medical, Munich, Germany) measurements, blood was drawn into 2-ml hirudin prefilled tubes (25 µg/ml) and rested for 30 min at room temperature before analysis as recommended by the manufacturer (time window 30–240 min). We performed testing using adenosine diphosphate (ADP Test 0.2 mM, Instrumentation Laboratory, Munich, Germany) and thrombin-related activation peptide (TRAP)-activating agents (TRAP test 1 mM, Instrumentation Laboratory). Technical details can be found elsewhere. Results are presented as area under the curve and the anaesthesiologist at the bedside was blinded to the results. Platelet counts and routine laboratory parameters [haemoglobin (Hb), INR, PTT, fibrinogen] were measured at the according time points.
STATISTICS Descriptive and explorative statistics were used for data analysis. The distribution of qualitative measures is presented by absolute and relative frequencies. Depending on the cell counts of corresponding contingency tables, group comparisons were performed by χ 2 tests or Fisher’s exact tests. Mean ± SD and median (interquartile range) are given for normally and non-normally distributed data, respectively. Accordingly, group comparisons were performed by t-tests and Mann–Whitney U-tests. The relation of quantitative measures was assessed by Spearman’s correlation coefficient. All statistical testing was performed on an explorative significance level of 0.05. Analysis was conducted using PASW Statistics for Windows Version 21.0 (IBM Corporation, Somer, NY, USA).
RESULTS Table 1 summarizes the demographic and surgical data. The severity of surgical intervention was comparable. No significant
Table 1: Demographics and surgical characteristics Neonates (n = 51) Demographics Patient characteristics Age (days) Weight (g) Height (cm) Male gender (%) PGE2 (%) Surgical characteristics Basic Aristotle score RACHS-1 score CPB time (min) DHCA (%)
Infants (n = 59)
Acyanotic (n = 20)
Cyanotic (n = 31)
Acyanotic (n = 40)
Cyanotic (n = 19)
9 (6–13) 3.2 ± 0.5 51 ± 4 10 (50%) 11 (55%)
12 (7–14) 3.3 ± 0.5 51 ± 3 17 (55%) 26 (84%)*
137 (106–179) 5.5 ± 1.4 62 ± 7 18 (45%) 2 (5%)
147 (106–192) 5.7 ± 1.5 61 ± 6 11 (58%) 2 (11%)
10.2 (10–11) 4 (4–6) 132 (106–169) 12 (60%)
10.8 (6.8–14.5) 4 (3–6) 95 (70–41)* 17 (55%)
6 (6–9) 2 (2–3) 85 (58–101) 3 (8%)
7.5 (7–8) 2 (2–3) 78 (52–93) 1 (5%)
Data are presented as median (interquartile range 25–75%) or absolute frequency (percentage). *P < 0.05 cyanotic versus acyanotic within age group. CPB: cardiopulmonary bypass; PGE2: prostaglandin E2; RACHS-1: risk-adjusted congenital heart surgery core; DHCA: deep hypothermic circulatory arrest.
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
differences between the two neonatal groups were observed except for shorter bypass and aortic cross-clamp times in cyanotic neonates. In the infant group, only 37% of cyanotic children required aortic clamping compared with 100% in the acyanotic group. There was a weak correlation of haemoglobin on baseline platelet function [Spearman Rho for Hb vs ADP (R = −0.401*, P = .025) and TRAP (R = −0.368*, P = 0.046)]. Cyanosis did not have any statistically significant effect on platelet function (Table 2).
303
However, in the infant group, baseline TRAP values for the acyanotic infant groups were lower than in the cyanotic infant [83 (64– 96) U vs 95 (79–101) U], though not statistically significant (P = 0.075). During the time on CPB, in vitro platelet function decreased significantly and recovered only partially by the end of Day 1 without any detectable influence of cyanosis. As for the laboratory values (Table 3), cyanotic infants had significantly higher baseline values of haemoglobin (P = 0.002) and fibrinogen
Table 2: Course of ADP and TRAP values Neonates (n = 51)
ADP (AU [U]) Baseline After protamine ICU arrival POD 1 TRAP (AU [U]) Baseline After protamine ICU arrival POD 1
Infants (n = 59)
Acyanotic (n = 20)
Cyanotic (n = 31)
P-value
Acyanotic (n = 40)
Cyanotic (n = 19)
P-value
86 (42–98) 16 (8–20)* 21 (11–37)* 57 (39–86)*
91 (77–101) 11 (6–20) * 18 (13–29)* 64 (33–93)*
0.306 0.411 0.586 0.864
68 (49–79) 15 (10–20)* 20 (11–28)* 45 (32–65)*
76 (63–85) 15 (10–23)* 16 (10–26)* 53 (34–64)*
0.178 0.715 0.521 0.823
96 (78–112) 23 (11–33)* 41 (22–71)* 77 (62–87)*
99 (88–109) 13 (8–22)* 34 (21–59)* 74 (77–98)*
0.721 0.222 0.405 0.846
83 (64–96) 25 (15–39)* 34 (25–54)* 56 (50–80)*
95 (79–101) 32 (21–43)* 37 (19–48)* 69 (60–84)*
0.075 0.166 0.846 0.226
Data are presented as median (interquartile range 25–75%) and P-values are within age groups. *P < 0.05 versus baseline. ADP: adenosine diphosphate; TRAP: thrombin receptor-activating peptide; AU [U]: area under curve; POD 1: postoperative day 1.
Table 3: Coagulation profile
Haemoglobin (g/dl) Baseline After protamine ICU arrival POD 1 Platelet count (103/µl) Baseline After protamine ICU arrival POD 1 INR Baseline After protamine ICU arrival POD 1 PTT (s) Baseline After protamine ICU arrival POD 1 Fibrinogen (mg/dl) Baseline After protamine ICU arrival POD 1
Infants
Acyanotic
Cyanotic
P-value
Acyanotic
Cyanotic
P-value
13.5 ± 2.2 12.4 ± 1.5 14.1 ± 3.2 15.4 ± 2.2*
13.2 ± 2.3 12.5 ± 2.0 14.5 ± 1.9* 15.2 ± 1.8*
0.609 0.760 0.494 0.966
11.7 ± 1.6 11.5 ± 1.6 12.9 ± 1.5* 13.9 ± 2.3*
13.3 ± 1.4 11.6 ± 1.3* 13.7 ± 1.9 14.2 ± 2.2
0.002 0.897 0.153 0.667
309 (262–358) 84 (56–126)* 146 (86–190)* 152 (106–207)*
303 (230–478) 81 (57–131)* 135 (80–178)* 141 (108–230)*
0.630 1.0 0.642 0.975
307 (261–387) 100 (84–133)* 117 (91–149)* 128 (89–176)*
343 (274–415) 110 (90–142)* 99 (78–135)* 134 (123–169)*
0.215 0.596 0.377 0.385
1.3 (1.1–1.4) 1.4 (1.4–1.9)* 1.2 (1.1–1.4) 1.2 (1.1–1.3)
1.1 (1.0–1.3) 1.6 (1.4–1.8)* 1.2 (1.1–1.3) 1.1 (1.0–1.2)
0.041 0.384 0.391 0.271
1.1 (1.0–1.1) 1.5 (1.3–1.6)* 1.2 (1.1–1.2)* 1.1 (1.1–1.2)*
1.1 (1.0–1.1) 1.4 (1.3–1.8)* 1.1 (1.1–1.2) 1.1 (1.1–1.2)
0.946 0.750 0.141 0.650
45 (40–54) 80 (54–150)* 54 (42–84) 48 (41–59)
46 (35–56) 67 (51–126)* 47 (41–60) 46 (37–65)
0.435 0.440 0.367 0.533
39 (35–43) 55 (48–66)* 45 (40–50)* 43 (38–51)*
39 (32–52) 59 (45–77)* 42 (38–51) 41 (36–66)
0.727 0.655 0.441 0.804
0.082 0.324 0.422 0.852
269 ± 116 181 ± 54* 200 ± 43* 304 ± 68
221 ± 90 162 ± 48* 202 ± 76 263 ± 64*
280 ± 111 180 ± 60* 228 ± 66 273 ± 61
324 ± 131 194 ± 57* 221 ± 53* 315 ± 82
0.018 0.365 0.200 0.436
Data are presented as mean ± SD and compared by t-test or median (interquartile range 25–75%) and compared by Mann–Whitney U-test, depending on the distribution. P-values are within age groups. *P < 0.05 versus baseline. ICU: intensive care unit; POD 1: postoperative day 1; INR: international normalized ratio; PTT: partial thromboplastin time.
CONGENITAL
Neonates
R. Gertler et al. / European Journal of Cardio-Thoracic Surgery
304
Table 4: Transfusion data and cumulative chest tube drainage Neonates (n = 51) n
Acyanotic (n = 20)
PRBC 1 14 2 1 ≥3 5 FFP 1 5 2 9 ≥3 6 Platelets 0 6 1 9 ≥2 5 Total exposures 2 2 3 6 4 5 ≥5 7 Cumulative CTD (ml/kg) 6h 17 (13–34) 24 h 41 (25–62)
Infants (n = 59) χ2
Acyanotic (n = 40)
Cyanotic (n = 19)
χ2
0.008
34 6 0
16 2 1
0.389
0.150
15 23 2
2 14 3
0.062
0.305
36 4 0
19 0 0
0.295
2 6 7 16
0.670
15 18 3 4
1 13 3 2
0.067
23 (13–37) 44 (27–53)
0.637 0.719
10 (7–13) 19 (15–26)
8 (4–13) 15 (9–28)
0.251 0.355
Cyanotic (n = 31)
10 13 8 2 15 14 16 9 6
Data are presented as absolute number of patients (n) and compared within groups by χ 2 test or Fisher’s exact test where indicated. CTD is shown as median (interquartile range 25–75%) and analysed by Mann–Whitney U-test. PRBC: packed red blood cells; FFP: fresh frozen plasma; CTD: chest tube drainage.
(P = 0.018). The coagulation profile was not statistically significantly different among acyanotic and cyanotic groups except for a higher INR at baseline in the cyanotic neonatal group. Transfusion requirements expressed as total number of exposures were similar within groups except for a statistically significant higher transfusion rate of PRBCs in the cyanotic newborn group (Table 4). Postoperative chest tube losses and the number of donor exposures were not statistically different within groups and not associated to platelet function or cyanosis. Overall baseline platelet function was a weak predictor of postoperative blood loss (Table 5). In neonates, ADP after protamine was related to CTD at 6 h after surgery and total blood product exposure in the first 24 h after ICU admission. In the same group, TRAP activity was weakly related to blood component exposure. For the infant group, ADP at the time of protamine infusion and upon ICU arrival correlated significantly with total blood exposure while TRAP was not significantly related to CTD and transfusion requirements.
Table 5: Spearman correlation coefficients and significance for platelet function vs blood loss and transfusion requirements
Neonates ADP baseline ADP after protamine ADP ICU admission TRAP baseline TRAP after protamine TRAP ICU admission
DISCUSSION We tested the association of cyanosis to baseline platelet aggregation during paediatric cardiac surgery and the time course of platelet function using the MULTIPLATE™ assay. The baseline platelet function was not significantly different in neonates and infants with or without cyanosis, and was a weak predictor of clinical blood transfusion requirements and postoperative CTD in cardiac surgery for children under 1 year of age.
Infants ADP baseline ADP after protamine ADP ICU admission TRAP baseline TRAP after protamine TRAP ICU admission
Platelet function and testing in neonates Platelet function of neonates is different from adults. Adhesion receptors are present early in foetal life, but become only fully
6h CTD
24 h CTD
Total exposures
r P-value r P-value r P-value r P-value r P-value r P-value
0.061 0.679 −0.301 0.037 −0.055 0.712 0.175 0.234 −0.236 0.107 −0.146 0.317
0.160 0.271 −0.141 0.340 0.073 0.622 0.208 0.156 −0.111 0.452 −0.052 0.723
−0.174 0.221 −0.323 0.024 −0.147 0.313 −0.020 0.893 −0.255 0.077 0.043 0.766
r P-value r P-value r P-value r P-value r P-value r P-value
−0.130 0.326 −0.204 0.121 −0.129 0.329 −0.152 0.254 −0.084 0.531 −0.106 0.425
−0.175 0.184 −0.251 0.055 −0.172 0.193 −0.218 0.100 −0.098 0.462 −0.135 0.309
−0.091 0.493 −0.442
