Rotational Thromboelastometry-Guided Transfusion Protocol to Reduce Allogeneic Blood Transfusion in Proximal Aortic Surgery With Deep Hypothermic Circulatory Arrest

Open AccessPublished:August 18, 2021DOI:https://doi.org/10.1053/j.jvca.2021.08.020

      Objectives

      To determine the impact of a rotational thromboelastometry (ROTEM)-guided transfusion protocol on the use of blood products, patient outcomes, coagulation factor concentrates, and costs.

      Design

      A single-center retrospective cohort study.

      Setting

      A tertiary university hospital.

      Patients

      Adults undergoing proximal aortic surgery with deep hypothermic circulatory arrest.

      Intervention

      ROTEM-guided transfusion protocol compared with clinically-guided transfusion.

      Measurements and Main Results

      Two hundred seventeen patients were included; seventy-one elective and 24 emergency patients in the clinically-guided group, and 59 elective and 63 emergency patients in the ROTEM-guided transfusion protocol group. In the ROTEM-guided transfusion protocol group, a significant reduction in transfusion of red blood cells (5 [3-8] v 2 [0-4], p < 0.001), platelet concentrate (2 [2-3] v 1 [1-2], p < 0.001), and plasma (1,980 mL [1,320-3,300] v 800 mL [0-1,000], p < 0.001) was seen in elective surgery. Emergency patients received fewer red blood cells (7 [5-10] v 5 [2-10], p = 0.040), platelet concentrate (3 [2-4] v 2 [2-3], p = 0.023), and plasma (3,140 mL [1,980-3,960] v 1,000 mL [0-1,400], p < 0.001). Prothrombin complex concentrate and fibrinogen concentrate were increased significantly in elective and emergency patients. The surgical reexploration for bleeding rate was decreased in elective patients 33.8% v 5.1%.

      Conclusion

      The implementation of a ROTEM-guided transfusion protocol might have the potential to decrease blood product transfusion and may improve patient outcomes.

      Key Words

      COMPLEX SURGERY of the proximal aorta often is performed with moderate hypothermic circulatory arrest (MHCA) with antegrade cerebral perfusion (ACP) or deep hypothermic circulatory arrest (DHCA).
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      Evaluation of the real-world impact of rotational thromboelastometry-guided transfusion protocol in patients undergoing proximal aortic surgery.
      However, studies on POC-guided transfusion strategies in proximal aortic surgery with DHCA are scarce. As mentioned above, these patients undergo profound coagulopathy, making it imperative to fill the knowledge gap in the existing body of literature.
      The objective of this study was to evaluate the effects of a protocolized ROTEM-guided transfusion strategy on the transfusion of blood products, surgical reexploration for bleeding, intensive care unit (ICU) LOS, hospital LOS, 30-day hospital mortality, administration of coagulation factor concentrates, and costs. The authors hypothesized that the implementation of a ROTEM-guided transfusion protocol in patients undergoing proximal aortic surgery with DHCA reduced the need for blood products and, therefore, may improve patient outcomes and reduce costs.

      Methods

       Study Design

      This study was a single-center retrospective cohort study in a tertiary university hospital in Rotterdam, the Netherlands. Approval by the medical ethical committee (Medical Ethical Committee Erasmus MC, Rotterdam, the Netherlands, Chairpersons Prof. Dr. H.J Metselaar and Prof. Dr. H.W. Tilanus) was granted on 26th of November, 2019, and registered with MEC-2019-0695. The study population included patients 18 years or older undergoing proximal aortic surgery (root, ascending aorta, and/or arch) with the use of DHCA, with an intraoperative minimum core temperature of ≤22°C. Both elective and emergency surgeries were included.
      In the clinically-guided transfusion group, patients undergoing surgery in 2013 and 2014 were included. During this period, transfusion management was guided by clinical judgment and standard laboratory tests. From 2015 onwards, ROTEM was used, but no formal ROTEM-guided transfusion protocol was implemented until mid-2016. In this period of time, ROTEM use was inconsistent. The second half of 2016 was needed to adjust to the new protocol. Thus, in the ROTEM-guided transfusion protocol group, patients undergoing surgery in the years 2017 and 2018 were included. During this period, the ROTEM-guided transfusion protocol was used to guide the transfusion of blood products and coagulation factor concentrates.

       Study Outcomes

      The primary outcomes were the transfusion of allogeneic blood products limited to transfusion during surgery and the first seven days following surgery. Blood products included RBCs, platelet concentrates, and plasma (FFP in 2013 and 2014, Omniplasma [Sanquin, Amsterdam, the Netherlands] in 2016, 2017, and 2018). Plasma transfusion volumes are presented as mL, as volume amounts differ between FFP (330 mL) and Omniplasma (200 mL). Both plasma products contain the same concentration of coagulation factors, resulting in no significant clinical implications.
      The secondary outcomes were surgical reexploration rates for bleeding in the first seven days following surgery, 30-day mortality, ICU LOS, hospital LOS, and costs of hospital care. The administration of prothrombin complex concentrate (PCC) (Cofact, Sanquin, Amsterdam, the Netherlands), fibrinogen concentrate (Haemocomplettan P, CSL Behring BV, Breda, the Netherlands), recombinant factor VIIa (rVIIa, NovoSeven; Novo Nordisk BV, Alphen aan den Rijn, The Netherlands), desmopressin (Minrin, Ferring BV, Hoofddorp, the Netherlands) and tranexamic acid (TXA, Cyklokapron, Pfizer BV, Capelle aan den IJssel, the Netherlands) during surgery and the first seven days following surgery and the incidence of transfusion-associated circulatory overload or transfusion-related acute lung injury also were secondary outcomes.

       Intraoperative Management

      Preoperative antiplatelet, antithrombotic therapy, and prophylactic antibiotic therapy were managed according to hospital protocol and were similar in both groups (Appendix A). There were no preoperative optimization measures taken. The standard monitoring for anesthesia was applied according to the American Society of Anesthesiologists protocols.

      Anesthesiologists ASo. Standards for basic anaesthetic monitoring. Available at: https://www.asahq.org/standards-and-guidelines/standards-for-basic-anesthetic-monitoring. Accessed 28 november 2019.

      Two large-bore intravenous needles were placed in the extremities, and an arterial line was placed in the radial artery. Induction was performed on the basis of hospital protocol using midazolam, propofol, sufentanil, muscle relaxants, and inotropes. Subsequently, a five-lumen central venous line was placed in the right jugular vein. A urine catheter with thermometry was placed, and a disposable nasal thermometer was placed in the nasopharynx. A probe for a transesophageal echocardiogram was inserted orally, and a bispectral index electrode and near-infrared spectroscopy were placed on the forehead.
      All patients received TXA. The clinically-guided transfusion cohort received 2 g of TXA before incision and 2 g of TXA prior to cardiopulmonary bypass (CPB). TXA could be repeated if deemed necessary by the anesthesiologist. In 2015, the hospital protocol for TXA administration was changed. The ROTEM-guided transfusion cohort received 1 g of TXA prior to incision, followed by 0.5 g of TXA continuously infused per hour until the end of surgery.
      Before the initiation of CPB, 300 units/kg of heparin were infused. CPB cannulae were placed in the ascending aorta for arterial access and in the right atrium for venous access. In the case of type A aortic dissections, arterial cannulae were placed in the femoral or subclavian artery. Retrograde autologous priming was not used. Systemic cooling was carried out with a maximum temperature gradient of 10°C between CPB and body temperature. Both the bladder and nasopharyngeal temperatures were continuously measured. The targeted temperature was determined at the discretion of the surgeon. The maximum duration of DHCA at a nasal temperature of 20°C was 30 minutes, and at a nasal temperature of 18°C, it was 45 minutes. ACP was used at the discretion of the surgeon or for a DHCA duration of >45 minutes. During DHCA, 100 g of Mannitol 15% (Baxter, Utrecht, the Netherlands) were infused. ACP (10 mL/kg/min for two cannulae or 7 mL/kg/min for one cannula) was applied through direct cannulation of the supraaortic vessels. Maximal accepted CPB line pressure was 120 mmHg. The right radial artery was preferentially used for cerebral blood pressure monitoring (max 40-70 mmHg) during ACP. Near-infrared spectroscopy recovery was closely monitored. Perfusion was restored after distal aortic repair, and rewarming was initiated with a temperature gradient of 10°C. In this period, 200 mL of Mannitol 15% and 100 mL of albumin 20% (Albuman; Sanquin Plasma Products BV, Amsterdam, The Netherlands) were added. Rewarming was discontinued once the bladder temperature reached 35.5°C-to-36.0°C. CPB management remained the same during the authors’ study period. During surgery, Cell Saver (Sorin XTRA Cell Saver, Sorin Group Deutschland GmbH, Munich, Germany) was used to minimize RBC transfusion. After surgery, all patients were transferred to the ICU.

       Laboratory Measurements

      Prior to the first incision, several laboratory tests were performed; namely, POC-activated clotting time (ACT) (HEMOCHRON Jr. Signature, International Technidyne Corporation, Edison NJ), POC arterial blood gas (ABL 90 FLEX PLUS, Radiometer Benelux BV, Zoetermeer, the Netherlands) with glucose, lactate, ionized calcium. Three minutes after the administration of heparin, POC ACT was repeated, with a target value more than 480 seconds. During CPB, electrolytes, hemoglobin (Hb), hematocrit count, blood gas values were measured continuously using CDI 500 (Terumo Europe NV, Leuven, Belgium). The test results were available for operating room personnel during weaning from CPB. Five minutes after the administration of protamine, ACT and arterial blood gas were repeated. Alongside the aforementioned analyses, fibrinogen, international normalized ratio (INR), prothrombin time (PT), and activated partial thromboplastin time were measured.

       Clinically-Guided Transfusion

      Before mid-2016, no transfusion-guiding protocol was present. Intraoperative management and laboratory measurements were comparable to the ROTEM-guided transfusion protocol group. In all patients, a TEG analysis (TEG 5000, Hemonetics, Braintree MA) with heparinase was conducted during CPB. In case of an emergency procedure, a baseline TEG analysis was performed before or right after induction. After the cessation of CPB, blood products were transfused if deemed necessary by the anesthesiologist. TEG analysis was repeated if deemed necessary. If bleeding persisted without a visible cause in the surgical field, the transfusion was conducted, awaiting laboratory results. A repeated dose of protamine was administered if ACT was prolonged more than 10% compared with baseline. After the administration of protamine and coagulation abnormality correction, TEG analysis was repeated when necessary. RBCs were transfused if hematocrit was 22% or lower during CPB. During weaning from CPB, the RBC transfusion trigger was established after deliberation among the anesthesiologist, cardiothoracic surgeon, and perfusionist, as there were no test modalities to monitor the patient during weaning. After weaning from CPB, RBCs were transfused when Hb was lower than 5.0 mmoL l–1. Platelet concentrate was transfused when platelet dysfunction was expected (due to DHCA, longer CPB) or if platelet counts were below 100 × 109L–1. Desmopressin was administered in case of sufficient platelet count but persistent bleeding due to suspected platelet dysfunction. Increased INR, PT, or low fibrinogen values served as indications to transfuse FFP. PCC was indicated in normovolemic patients, using vitamin K antagonists with prolonged PT and INR. In patients with normal PT or INR and low fibrinogen levels, fibrinogen concentrate was given.

       ROTEM-Guided Transfusion Protocol

      The intraoperative ROTEM-guided transfusion protocol can be found in Figure 1. The intraoperative ROTEM-guided transfusion protocol implemented in the authors’ hospital was based on the protocol presented in the study of Görlinger et al.
      • Gorlinger K
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      Subtle adjustments were made by the protocol committee to improve utility in their hospital. The committee consisted of a cardiothoracic anesthesiologist, a cardiothoracic surgeon, and an intensive care physician. The protocol for the management of postoperative bleeding in the ICU is a hospital-made protocol, in which the ROTEM-based correction of coagulopathy is based on the protocol described in the Weber trial.
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      RBC transfusion triggers were equal to the clinically-guided transfusion strategy. ROTEM analysis (ROTEM Delta, TEM International GmbH, Munich, Germany) was performed at 32°C during the rewarming phase on CPB. If necessary, after the administration of protamine and coagulation products, ROTEM analysis was repeated.
      Fig 1
      Fig 1ROTEM-guided transfusion protocol in the intensive care unit. APTT, activated 11 partial thromboplasmin time; DHCA, deep hypothermic circulatory arrest; Hb, hemoglobin; INR, international normalized ratio; LVAD, left ventricular assist device; PCC, prothrombin complex concentrate; RBC, red blood cell; ROTEM, rotational thromboelastometry; rVIIa, recombinant factor VIIa.
      In the ICU, the intensivist determined the presence of microcapillary bleeding and acted according to protocol (Appendix B1). After the correction of the coagulation abnormality, ROTEM analysis was repeated until adequate hemostasis was obtained.

       Potential Costs

      The costs of blood products, coagulation factor concentrates, TEG and ROTEM assessments, and re-thoracotomy in the first seven days were calculated. Additionally, prices for the total LOS in the ICU and the LOS in the general ward were calculated. The prices for all variables are confirmed prices in the authors' hospital. The cost for surgical reexploration was calculated by a financial employee of the authors' hospital. Appendix C1 shows the prices for cost calculation. Medians of the abovementioned costs were used to calculate costs per patient.

       Statistical Analysis

      Data were stratified for elective and emergency surgery. Visual inspection of histograms and Kolmogorov-Smirnov testing were applied to determine normality in distribution. All continuous variables are presented as median (interquartile range), and discrete variables are presented as count (%). For normally distributed data, an unpaired two-sided Student t-test was used for analysis. In continuous data with skewed distribution, the Mann-Whitney U test was used for analysis. For discrete data, Pearson's chi-squared testing and Fisher exact test were used. Multivariate regression models were used to assess the association of ROTEM-guided transfusion with the outcome. The effect modification of emergency surgery was tested and dropped if not significant. For all models, adjustments for potentially-associated factors were included, with a p-value <0.1 in a univariate regression. In a multivariate logistic regression model, the associations of clinical variables and ROTEM-guided transfusion with rethoracotomy were determined. Multivariate linear regression was calculated to assess the association with blood product transfusion. An assumption of normal distribution of residuals was checked. P-values ≤0.05 were considered statistically significant. All statistical analyses were performed in Statistical Package for the Social Sciences (SPSS version 26.0 for Mac OS, IBM corp., Armonk NY).

      Results

       Baseline Characteristics

      A total of 217 patients were included. Seventy-one elective and 24 emergency patients underwent surgery using clinically-guided transfusion, and 59 elective and 63 emergency patients underwent surgery with a ROTEM-guided transfusion strategy. Table 1 displays the baseline characteristics. Significant differences existed regarding European System for Cardiac Operative Risk Evaluation 2 (euroSCORE 2) in elective surgery.
      Table 1Baseline Characteristics
      Elective SurgeryEmergency Surgery
      Clinically-Guided Transfusion (n = 71)ROTEM-Guided Transfusion (n = 59)p -valueClinically-Guided Transfusion (n = 24)ROTEM-Guided Transfusion (n = 63)p -value
      Age, y (IQR)67 (61-72)63 (57-73)0.26464 (55-68)63 (53-73)0.951
      Gender ratio (male/female)39/3218/410.08916/824/390.681
      BSA (IQR)1.94 (1.76-2.13)2.02 (1.83-2.23)0.1172.00 (1.91-2.23)1.95 (1.82-2.13)0.666
      Missing, n (%)0 (0.0)0 (0.0)0 (0.0)1 (1.6)
      EuroSCORE 2 (IQR)4.80 (2.84-7.03)3.07 (2.21-4.88)0.0069.47 (4.16-17.19)10.12 (6.07-17.45)0.401
      Previous cardiac surgery, n (%)8 (11.3)6 (10.2)0.8410 (0.0)3 (4.8)0.558
      Previous aortic surgery, n (%)7 (9.9)5 (8.5)1.0002 (8.3)3 (4.8)0.613
      Lung disease, % n (%)11 (15.5)12 (20.3)0.4712 (8.3)5 (7.9)1.000
      Neurologic dysfunction, n (%)9 (12.7)5 (8.5)0.5733 (12.5)8 (12.7)1.000
      Diabetes, n (%)5 (7.0)7 (11.9)0.3771 (4.2)0 (0.0)0.276
      Hepatopathy, n (%)0 (0.0)1 (1.7)0.4540 (0.0)1 (1.6)1.000
      Operative procedure n (%)
      Hemiarch replacement57 (80.3)53 (89.8)0.13322 (91.7)53 (84.1)0.362
      Total arch replacement14 (19.7)6 (10.2)0.1332 (8.3)10 (15.9)0.362
      Concomitant CABG14 (19.7)8 (13.6)0.3511 (4.2)2 (3.2)1.000
      Aortic valve procedure39 (54.9)36 (61.0)0.48411 (45.8)21 (33.3)0.280
      Mitral valve procedure3 (4.3)1 (1.7)0.6260 (0.0)0 (0.0)NA
      Type A aortic dissectionNANANA23 (95.8)62 (98.4)0.473
      Preoperative values
      Hemoglobin, mmoL l−1 (IQR)8.2 (7.5-8.8)8.1 (6.8-8.7)0.2498.2 (7.8-8.8)7.9 (7.0-8.9)0.092
      Missing, n (%)0 (0.0)0 (0.0)0 (0.0)1 (1.6)
      Platelet count, billion l–1 (IQR)224 (188-277)220 (179-257)0.887188 (148-227)198 (154-240)0.762
      Creatinine, µmol l–1 (IQR)90 (67-112)88 (74-100)0.96896 (81-111)98 (73-124)0.740
      Fibrinogen, g l–1 (IQR)3.8 (3.0-4.3)3.4 (2.8-3.8)0.0583.1 (1.9-4.0)2.1 (1.6-2.8)0.076
      Missing, n (%)7 (9.9)2 (3.4)12 (50.0)32 (51.2)
      Continuous data are presented as median (IQR), ratios are presented as count (%).
      Abbreviations: BSA, body surface area; CABG, coronary artery bypass grafting; IQR, interquartile range; ROTEM, rotational thromboelastometry; NA, not available.

       Intraoperative and Postoperative Values

      For most intraoperative and postoperative values, there were no significant differences between the patient groups (Table 2). Differences were observed in the elective surgery patient group; a longer CPB duration was found in the patients who received protocolized ROTEM-guided transfusion. There were no significant differences in the rates of antegrade cerebral perfusion, autologous blood return, and DHCA duration (Table 2). Patients in the ROTEM-guided protocol group undergoing elective surgery had longer CPB duration, higher postoperative Hb, and lower postoperative fibrinogen. The platelet count was similar in both groups. Emergency patients had no substantial differences in postoperative laboratory values.
      Table 2Intraoperative and Postoperative Variables
      Elective SurgeryEmergency Surgery
      Clinically-Guided Transfusion (n = 71)ROTEM-Guided Transfusion (n = 59)p -valueClinically-Guided Transfusion (n = 24)ROTEM-Guided Transfusion (n = 63)p -value
      Intraoperative variables
      Antegrade cerebral perfusion, n (%)14 (19.7)16 (27.1)0.31911 (45.8)17 (27.0)0.124
      Autologous blood returned, mL (IQR)915 (505-1,350)1050 (650-1,600)0.2201130 (660-1,780)1430 (880-1,960)0.169
      Intraoperative minimum temperature,°C (IQR)19.5 (18.2-20.1)19.6 (18.0-21.4)0.59518.0 (17.3-18.4)18.0 (18.0-20.0)0.006
      CPB duration, min (IQR)193 (170-227)224 (178-290)0.025243 (202-296)258 (219-317)0.262
      DHCA duration, min (IQR)17 (14-28)20 (15-45)0.11438 (29-62)32 (28-43)0.382
      Postoperative variables
      Hemoglobin, mmoL l–1 (IQR)6.2 (5.7-6.7)6.6 (6.1-7.4)0.0176.4 (5.7-7.0)6.8 (6.1-7.5)0.134
      Missing, n (%)0 (0.0)1 (1.7)0 (0.0)1 (1.6)
      International normalized ratio (IQR)1.4 (1.3-1.5)1.5 (1.4-1.6)0.0251.4 (1.2-1.6)1.4 (1.2-1.6)0.794
      Missing, n (%)3 (4.2)2 (3.4)0 (0.0)2 (3.4)
      Platelet count, billion l–1 (IQR)118 (97-141)121 (95-147)0.76990 (77-114)104 (82-132)0.180
      Missing, n (%)2 (2.8)2 (3.4)0 (0.0)4 (6.3)
      Fibrinogen, g l–1 (IQR)2.3 (2.0-2.6)2.0 (1.7-2.2)<0.0012.0 (1.6-2.5)1.8 (1.6-2.2)0.211
      Missing, n (%)6 (8.5)1 (1.7)0 (0.0)0 (0.0)
      Continuous data are presented as median (IQR), ratios are presented as count (%).
      Abbreviations: CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; IQR, interquartile range.

       Primary and Secondary Outcomes

      The primary and secondary outcomes are presented in Table 3. Elective and emergency patients who underwent surgery after implementation of the ROTEM-guided transfusion protocol received significantly fewer RBCs, platelet concentrates, and plasma, whilst an increase in the use of PCC and fibrinogen concentrate was seen.
      Table 3Primary and Secondary Outcomes
      Elective surgeryEmergency surgery
      Clinically-Guided Transfusion (n = 71)ROTEM-Guided Transfusion (n = 59)p -valueClinical-Guided Transfusion (n = 24)ROTEM-Guided Transfusion (n = 63)p -value
      Primary outcomes
      Red blood cells, units (IQR)5 (3-8)2 (0-4)<0.0017 (5-10)5 (2-10)0.040
      Platelet concentrate, units (IQR)2 (2-3)1 (1-2)<0.0013 (2-4)2 (2-3)0.023
      Plasma volume, mL (IQR)1,980 (1,320-3,300)800

      (0-1,000)
      <0.0013,140 (1,980-3,960)1,000

      (0-1,400)
      <0.001
      Secondary outcomes
      PCC, international units (IQR)0 (0-0)0 (0-1,000)<0.0010 (0-0)1,000 (0-1,625)<0.001
      PCC, n (%)2 (2.8)21 (35.6)<0.0013 (12.5)45 (71.4)<0.001
      Fibrinogen concentrate, mg (IQR)0 (0-0)4 (2-6)<0.0010 (0-3)6 (4-8)<0.001
      Fibrinogen concentrate, n (%)14 (19.7)50 (84.7)<0.00111 (45.8)61 (96.8)<0.001
      Tranexamic acid, g (IQR)4 (4-6)6 (4.5-6.5)0.0196 (4-7.5)5 (5-6)0.076
      Tranexamic acid, n (%)71 (100)59 (100)NA24 (100)63 (100)NA
      Desmopressin, µg (IQR)0 (0-24)0 (0-0)0.0040 (0-0)0 (0-0)0.229
      Desmopressin, n (%)26 (36.6)9 (15.3)0.0065 (20.8)7 (11.1)0.240
      rVIIa, µg00NA00NA
      rVIIa, n (%)0 (0.0)0 (0.0)NA0 (0.0)0 (0.0)NA
      ICU length of stay, d (IQR)1 (1-3)1 (1-2)0.1643 (2-6)2 (1-6)0.614
      Hospital length of stay, d (IQR)8 (6-12)6 (4-8)<0.00111 (7-21)10 (7-17)0.739
      Surgical re-exploration, n (%)24 (33.8)3 (5.1)<0.0016 (25.0)11 (17.5)0.428
      30-day mortality, n (%)2 (2.9)3 (5.1)0.6594 (16.7)11 (17.5)1.000
      Transfusion-related acute lung injury, n (%)0 (0.0)0 (0.0)NA0 (0.0)0 (0.0)NA
      Transfusion-associated circulatory overload, n (%)0 (0.0)0 (0.0)NA0 (0.0)0 (0.0)NA
      Blood products and coagulation factor concentrates that are administered in the first seven days after surgery. Continuous data are presented as median (IQR), ratios are presented as count (%).
      Abbreviations: ICU, intensive care unit; IQR, interquartile range; NA, not available; PCC, prothrombin complex concentrate; ROTEM, Rotational thromboelastometry; rVIIa, recombinant factor VIIa.
      In elective surgery, decreases in surgical reexploration rates (33.8% v 5.1%, p < 0.001) and shorter median hospital LOS (8 v 6 days, p < 0.001) were observed. In both elective and emergency surgeries, there were no significant differences in ICU LOS and 30-day mortality. Emergency patients had no difference in surgical reexploration rates.
      Increases of median PCC and fibrinogen concentrate administration were found in elective and emergency surgery after the implementation of the ROTEM-guided transfusion protocol. Median TXA administration was higher, and desmopressin administration was lower in the elective ROTEM-guided protocol group. No patient received rVIIa.

       Regression Analyses

      In a multivariate regression analysis of blood product use, a negative association between the ROTEM-guided transfusion protocol and the transfusion of RBCs, platelet concentrates, and plasma volume was observed (Table 4). The ROTEM-guided protocol was associated with a decrease of 3.52 units of RBC (β-3.52, [95% CI –4.89 to –2.17]; p ≤ 0.001), adjusting for other potential confounding factors. CPB duration was associated with increased transfusions of RBCs, platelet concentrate, and plasma volume. Other factors associated with RBC transfusion are preoperative Hb and DHCA duration. The EuroSCORE 2 was slightly associated with increases of RBC and platelet concentrate transfusion. Previous aortic surgery was associated with increased transfusion of plasma (β 9.64 [95% CI 2.69-16.60]).
      Table 4Multivariate Linear Regression Analysis of Association With Blood Product Transfusion
      β CoefficientConfidence Interval (95%)P-value
      Red blood cells
      ROTEM-guided transfusion strategy–3.52–4.89 to –2.17<0.001
      Preoperative hemoglobin–0.97–1.52 to –0.410.001
      Emergency procedure0.09–1.60 to 1.430.911
      EuroSCORE 20.100.03-0.170.007
      Previous cardiac surgery–1.62–4.47 to 1.220.262
      Previous aortic surgery2.11–0.65 to 4.870.134
      CPB duration0.470.38-0.57<0.001
      DHCA duration–0.13–0.25 to –0.010.034
      Platelet concentrate
      ROTEM-guided transfusion strategy–1.11–1.53 to –0.69<0.001
      Preoperative platelet count–0.05–0.08 to –0.03<0.001
      Emergency procedure–0.31–0.79 to 0.170.209
      EuroSCORE 20.030.01-0.060.003
      Previous cardiac surgery–0.27–1.16 to 0.620.551
      Previous aortic surgery0.53–0.33 to 1.390.224
      CPB duration0.140.11-0.17<0.001
      DHCA duration–0.04–0.07 to 0.000.059
      Plasma volume
      ROTEM-guided transfusion strategy–24.65–26.55 to –20.76<0.001
      EuroSCORE 20.18–0.02 to 0.380.073
      Previous cardiac surgery–5.39–13.63 to 2.850.20
      Previous aortic surgery11.433.24-19.620.006
      CPB duration1.190.90-1.48<0.001
      DHCA duration–0.19–0.54 to 0.160.283
      Multivariate linear regression analysis of blood product use. Plasma volume is categorized per 100 mL, CPB duration is categorized per ten minutes, DHCA duration is categorized per five minutes.
      Abbreviations: BSA, body surface area CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; ROTEM, rotational thromboelastometry.
      In the multivariate logistic regression, ROTEM-guided transfusion protocol was associated with an 82% reduction in the odds of requiring surgical reexploration for bleeding adjusting for other potential confounding factors (odds ratio 0.18 [95% CI 0.07–0.45]) (Table 5).
      Table 5Multivariate Logistic Regression for Odds of Redo Thoracotomy
      Odds RatioConfidence Interval (95%)P-value
      Multivariate logistic regression
      ROTEM-guided transfusion protocol0.180.07-0.45< 0.001
      Previous aortic surgery3.010.91-9.340.070
      Intraoperative minimum temperature0.920.71-1.190.510
      CPB duration1.041.00-1.090.076
      Preoperative creatinine1.070.98-1.190.162
      ROTEM * Emergency surgery1.240.71-2.140.452
      ECC duration is categorized per ten minutes, DHCA duration is categorized per five minutes, preoperative creatinine is categorized per ten units.
      Abbreviations: CPB, cardiopulmonary bypass; DHCA, deep hypothermic circulatory arrest; ROTEM, rotational thromboelastometry.

       Costs

      A ROTEM-guided transfusion protocol potentially could save $5,421.04 per patient undergoing elective surgery and $578.12 per patient undergoing emergency surgery (Table 6). This reduction in costs mainly was attributable to decreased hospital-related costs. The reduction in allogeneic transfusion products was negated by raised prohemostatic medication.
      Table 6Estimation of Costs and Potential Savings in Dollars Per Patient Due to a ROTEM-Guided Transfusion Protocol
      Elective SurgeryEmergency Surgery
      Clinically-Guided Transfusion (n = 71)ROTEM-Guided Transfusion (n = 59)Potential savingsClinically-Guided Transfusion (n = 24)ROTEM-Guided Transfusion (n = 63)Potential savings
      Allogeneic transfusion products (total)4,487.61 (3,156.39; 7,083.80)2,089.97 (1,167.85; 3,179.58)2,397.646,642.90 [4,623.81; 8,458.16)3,451.98 (2,167.49; 6,015.10)3,190.92
      Red blood cells1,362.02 (817.21; 2,179.22)544.81 (0.00; 1,089.61)817.211,906.82 (1,362.02; 2,587,83)1,362.02 (544.81; 2,724.03)544.81
      Plasma1,542.02 (1,028.02; 2,570.04)623.04 (0.00; 778.80)918.982,441.54 (1,542.02; 3,084.05)778.80 (0.00; 1,090.32)1,662.74
      Platelet concentrate1,311.17 (1,311.17; 1,966.75)655.58 (655.58; 1311,17)655.581,966.75 (1,311.17; 2,622.34)1,311.17 (1,311.17; 1,966,75)655.58
      Prohemostatic medication (total)60.75 (40.50; 122.15)2,316.43 (1,198.71; 3,459.88)–2,255.69362.63 (60.99; 1,727.20)4,531.62 (3,404.84; 7,199.85)–4,169.00
      Desmopressin0.00 (0.00; 30.87)0.00 (0.00;0.00)0.000.00 (0.00;0.00)0.00 (0.00;0.00)0.00
      Tranexamic acid40.50 (40.50; 60.75)60.75 (45.45; 66.01)–20.2560.75 (50.62; 75.93)50.62 (50.62; 60.75)10.12
      Fibrinogen concentrate0.00 (0.00; 0.00)2,235.44 (1,117.72; 3,353.16)–2,235.440.00 (0.00; 0.00)3,353.16 (2,235.44; 4,470.88)–3,353.16
      Prothrombin complex concentrate0.00 (0.00; 0.00)0.00 (0.00; 0.00)0.000.00 (0.00; 0.00)1054,68 (0.00; 2,109.37)–1,054.68
      Laboratory tests (total)59.00 (59.00; 59.00)346.45 (346.45; 519.67)–287.4559.00 (59.00; 59.00)519.67 (346.45; 692.90)–460.67
      ROTEM0.00 (0.00; 0.00)346.45 (346.45; 519.67)–346.450.00 (0.00; 0.00)519.67 (346.45; 692.90)–519.67
      TEG59.00 (59.00; 59.00)0.00 (0.00; 0.00)59.0059.00 (59.00; 59.00)0.00 (0.00; 0.00)59.00
      Hospital costs (total)12,272.00 (7,316.00; 19,914.10)6,608.00 (5,192.00; 12,744.00)5,664.0018,925.05 [11,092.00; 32,186.10)15,340.00 (8,968.00; 29,444.21)3,585.05
      ICU length of stay3,068.00 (3,068.00; 9,204.00)3,068.00 (3,068.00; 6,136.00)0.009,204.00 (4,602.00; 16,874.00]6,136,00 (3,068.00; 18.408.00)3,068.00
      Regular ward length of stay4,248.00 (3,540.00; 6,372.00)2,832.00 (2,124.00; 4,956.00)1,416.006,018.00 (2,832.00;10.266.00)4,956.00 (2,832.00; 8,496.00)1,062.00
      Surgical re-exploration0.00 (0.00; 85,861.10)0.00 (0.00; 0.00)0.000.00 (0.00; 4,293.05)0.00 (0.00; 0.00)0.00
      Total costs$17,113.37 (10,795.35; 27,606.44)$11,692.34 (9,893.84; 17,964.99]$5,421.04$24,931.23 (17,369.59; 44,442.45)$24353,11 (17,341.34; 39,900.01)$578.12
      Medians and interquartile range are presented.
      Abbreviations: ROTEM, rotational thromboelastometry; ICU, intensive care unit.

      Discussion

      Findings in this study supported the authors’ hypothesis; after the implementation of a ROTEM-guided transfusion protocol, decreases in the transfusion of RBCs, platelet concentrates, and plasma were seen in both elective and emergency surgery. In elective surgery patients, significant decreases in surgical reexploration rates and hospital LOS were found, while no differences in ICU LOS and 30-day mortality were displayed. Overall, patients in the ROTEM-guided protocol group received more PCC and fibrinogen concentrate. This showed that the implementation of a ROTEM-guided transfusion protocol resulted in a reallocation of resource utilization.
      RBC and plasma transfusion were reduced in the ROTEM-guided transfusion protocol group. Previous studies showed similar findings in proximal aortic surgery with DHCA.
      • Girdauskas E
      • Kempfert J
      • Kuntze T
      • et al.
      Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: A prospective, randomized trial.
      ,
      • Fassl J
      • Matt P
      • Eckstein F
      • et al.
      Transfusion of allogeneic blood products in proximal aortic surgery with hypothermic circulatory arrest: Effect of thromboelastometry-guided transfusion management.
      ,
      • St-Onge S
      • Lemoine É
      • Bouhout I
      • et al.
      Evaluation of the real-world impact of rotational thromboelastometry-guided transfusion protocol in patients undergoing proximal aortic surgery.
      However, these studies were not confined to patients undergoing DHCA but also MHCA. In both elective as well as emergency surgery, a median decrease of three and two RBC concentrates was found, respectively. Despite decreased RBC transfusion, the postoperative Hb was higher in the elective surgery ROTEM-guided transfusion protocol group. Decreased dilution effect due to less plasma transfusion was a possible explanation for this finding.
      Interestingly, plasma transfusion still occurs frequently, even though it is not included in the ROTEM-guided transfusion protocol. This most likely is due to the extensive blood loss, and, in this context, repeated crystalloid infusion is not desirable. Lack of protocol adherence also might influence plasma transfusion.
      In the authors’ study, platelet concentrate transfusion was reduced after the introduction of the ROTEM-guided transfusion protocol. However, this finding is not consistent with the current literature.
      • Girdauskas E
      • Kempfert J
      • Kuntze T
      • et al.
      Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: A prospective, randomized trial.
      ,
      • Fassl J
      • Matt P
      • Eckstein F
      • et al.
      Transfusion of allogeneic blood products in proximal aortic surgery with hypothermic circulatory arrest: Effect of thromboelastometry-guided transfusion management.
      ,
      • St-Onge S
      • Lemoine É
      • Bouhout I
      • et al.
      Evaluation of the real-world impact of rotational thromboelastometry-guided transfusion protocol in patients undergoing proximal aortic surgery.
      In elective and emergency patients, a median decrease of one unit of platelet concentrate was observed, while no decrease of platelet concentrate transfusion was seen in other studies. This difference could be explained by a difference in depth of hypothermia, but other contributing factors could be casemix, emergency procedures, and consequently prolonged CPB time or institutional differences in transfusion approaches.
      The EuroSCORE 2 differed significantly in elective patients between the two different transfusion strategies. Although a higher euroSCORE 2 was associated with increased RBC and platelet concentrate transfusion, ROTEM-guided transfusion protocol was more strongly associated with the transfusion of RBC and platelet concentrate compared with euroSCORE. Therefore, the authors hypothesized that euroSCORE 2 differences in elective patients has no strong impact on transfusion of blood products in elective surgery patients.
      In elective surgery patients, the surgical reexploration for bleeding rate was lower in the ROTEM-guided transfusion protocol group. This decrease in surgical reexploration might have been caused by an efficient reversal of coagulation abnormalities. The surgical reexploration rate of 33.8% in the clinically-guided transfusion group was conspicuous compared with a rate of 24% reported by Girdauskas et al.
      • Girdauskas E
      • Kempfert J
      • Kuntze T
      • et al.
      Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: A prospective, randomized trial.
      Because the study hospital is relatively large, changes in the surgical team have occurred. This might have contributed to differences in postoperative bleeding incidence and decision-making for surgical reexploration. However, the minimum core temperature in the authors’ study population was significantly lower, increasing the risk of bleeding.
      • Martini WZ
      • Pusateri AE
      • Uscilowicz JM
      • et al.
      Independent contributions of hypothermia and acidosis to coagulopathy in swine.
      When comparing the different strategies in the emergency surgery groups, the decrease in surgical reexploration rate was not significant, even though a 7.5% reduction was seen. Possible explanations may be a relatively small sample size or a more profound dysregulation of the primary hemostasis in these groups due to active bleeding or an inability to stop platelet aggregation inhibitors, which is not detected by ROTEM.
      • Korpallová B
      • Samoš M
      • Bolek T
      • et al.
      Role of thromboelastography and rotational thromboelastometry in the management of cardiovascular diseases.
      This could argue for the use of POC tests to detect platelet aggregation dysfunction in emergency surgical patients who use antiplatelet drugs, which would ensure extensive insight into patients’ coagulation status. Unfortunately, studies assessing their value in therapeutic decisions in bleeding patients after cardiac surgery are scarce.
      • Bolliger D
      • Lancé MD
      • Siegemund M.
      Point-of-care platelet function monitoring: Implications for patients with platelet inhibitors in cardiac surgery.
      Additionally, consumption coagulopathy, caused by the dissected aorta in emergency surgery, could explain the persistence of coagulopathy even after attempted correction, as it concerns primary hemostasis.
      • Arturo E
      • Eric MI
      • Eduardo B
      • et al.
      Insights from the international registry of acute aortic dissection.
      • Boening A
      • Karck M
      • Conzelmann LO
      • et al.
      German registry for acute aortic dissection type A: Structure, results, and future perspectives.
      • Geirsson A
      • Ahlsson A
      • Franco-Cereceda A
      • et al.
      Hospital volumes and later year of operation correlates with better outcomes in acute Type A aortic dissection.
      • ten Cate JW
      • Timmers H
      • Becker AE.
      Coagulopathy in ruptured or dissecting aortic aneurysms.
      The presence of increased coagulopathy in aortic dissections was supported by the authors’ finding of increased administration of PCC and fibrinogen concentrate in emergency patients in comparison to elective patients.
      Thirty-day mortality or ICU LOS were comparable between the two transfusion strategy groups. A systematic review of 8,332 patients on POC-guided transfusion strategy in cardiac surgery and a study conducted by Girdauskas et al had congruent findings.
      • Girdauskas E
      • Kempfert J
      • Kuntze T
      • et al.
      Thromboelastometrically guided transfusion protocol during aortic surgery with circulatory arrest: A prospective, randomized trial.
      ,
      • Deppe A-C
      • Weber C
      • Zimmermann J
      • et al.
      Point-of-care thromboelastography/thromboelastometry-based coagulation management in cardiac surgery: A meta-analysis of 8332 patients.
      Patients undergoing elective surgery had a median decrease of two days in hospital LOS. However, besides the ROTEM-guided protocol, decreased hospitalization was likely to be ascribed to organizational changes over time alongside earlier discharge to referral hospitals.
      In elective surgery, the estimate of total median costs per patient was $5,421.04 lower. The decrease in potential costs for elective patients primarily is achieved by reductions in blood product transfusion and hospital-related costs. The reduction in allogeneic transfusion products was negated by raised prohemostatic medication. In emergency surgery, a modest median saving of $578.12 was found. This was attributable to an increased coagulation factor concentrate administration despite reduced hospital-related and allogeneic transfusion products costs. Another possible explanation was a small sample size in the clinically-guided emergency surgery group, prompting the cost analysis to be underpowered to detect differences. Overall, caution is warranted because there are large differences in costs for healthcare between different countries.

       Study Limitations

      Despite robust analysis methods used for this study, limitations were inevitable, mostly due to the retrospective nature of this study. First, a limitation was the lack of a clear transfusion protocol based on conventional coagulation parameters and TEG (without a fibrinogen assay) before the introduction of ROTEM. Without a protocol, there could be less awareness of harmful transfusion-related side-effects, leading to an unnecessary transfusion. The implementation of a transfusion protocol will increase awareness. It could be expected that the reduction of transfusions is an effect of successful implementation of a protocol rather than an effect of ROTEM per se. ROTEM and TEG results are significantly faster than conventional laboratory tests. Consequently, when ROTEM results with a fibrinogen assay become clear, they correspond better to the hemostatic condition of the patient.
      Furthermore, because this was a single-center study, the results cannot be generalized to other institutions without caution. In addition, temporal bias could influence surgical technique, surgeon's experience, and perioperative management, which may well have influenced the results of this study, given the time interval between the conventional and transfusion protocol groups. Moreover, no data on possible thromboembolic complications were present, preventing the possibility to draw conclusions on the effects of a ROTEM-guided transfusion protocol on thromboembolic complications.

      Conclusions

      This was the first study to investigate the effects of a ROTEM-guided transfusion protocol in patients undergoing proximal aortic surgery with DHCA rather than MHCA. In the authors’ study population, a reduction in blood product transfusion was seen in the group with protocolized transfusion guided by ROTEM. In elective patients, there was a significant reduction in surgical reexploration for bleeding. In all patients, no reductions of ICU LOS and 30-day mortality were found. The implementation of a ROTEM-guided transfusion protocol might have the potential to decrease blood product transfusion and may improve patient outcomes in patients undergoing high-risk cardiac and proximal aortic procedures with DHCA.

      Conflict of Interest

      None.

      Appendix. Supplementary materials

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