Turk J Anaesthesiol Reanim 2017; 45: 87-92 DOI: 10.5152/TJAR.2017.74875 A Comparison of the Effects of 20% Mannitol and 3% NaCl on Coagulation Parameters In Vitro using ROTEM: A Prospective Randomized Crossover Study %20 Mannitol ve %3 NaCL Solüsyonlarının Koagulasyon Parametereleri Üzerine Etkisinin İn Vitro Original Article Araştırma Original / Özgün Olarak Karşılaştırılması: Prospektif, Randomize Çapraz Çalışma Achmet Ali1, Bilge Şencan1, Pulat Akın Sabancı2, Demet Altun1, Aylin Tetik1, Lerzan Recep Doğan1, İbrahim Özkan Akıncı1 1Department of Anaesthesiology, İstanbul University İstanbul School of Medicine, İstanbul, Turkey 2Department of Neurosurgery, İstanbul University İstanbul School of Medicine, İstanbul, Turkey Objective: The aim of the present study is to compare the effect of Amaç: Bu çalışmada %20 Manitol ve %3 NaCl’nin in vitro 20% mannitol and 3% NaCl on blood coagulation in vitro using ortamda koagülasyon üzerine etkilerini karşılaştırmayı amaç- rotational thromboelastometry (ROTEM). ladık. Methods: Twenty-millilitre blood samples were obtained from 15 Yöntemler: On beş gönüllünün her birinden 20 mL kan örne- Abstract Abstract / Öz volunteers. In each group, 2 mL blood samples were collected into ği alındı. Her grupta rotasyonel tromboelastometri (ROTEM) both polypropylene tubes and EDTA tubes for ROTEM and he- ve hemogram analizi için 2’şer mL kan örneği polipropilen ve mogram analysis. After sampling, blood samples were diluted with EDTA tüplerinde toplandı. Örnekleme sonrası kan örnekleri test test solutions. Group C (control): Only blood, Group M (man- solüsyonları ile seyreltildi. Grup K (Kontrol): sadece kan, Grup nitol): 7% vol 20% mannitol concentration in the blood, Group M (Mannitol): Kan içinde %7 konsantrasyonda %20 mannitol, hypertonic saline (HS): 7% vol 3% hypertonic saline (NaCl) in Grup hipertonik salin (HS): Kan içinde %7 konsantrasyonda %3 the blood, Group M/H (mannitol and hydroxyethyl starch solu- hipertonik salin, Grup M/H (Mannitol ve HES): Kan içinde %7 tions [HES]): 6% vol 20% mannitol concentration and 8% vol konsantrasyonda %20 mannitol ve %8 konsantrasyonda HES, HES in the blood and Group HS/H (hypertonic saline and HES): Grup HS/H (Hipertonik Salin ve HES): Kan içinde %7 konsant- 6% vol 3% hypertonic saline concentration and 8% vol HES in rasyonda %3 hiperetonik salin ve %8 konsantrasyonda HES. Bu the blood. The following thromboelastometric parameters were işlem sonrası İnTEM'de pıhtılaşma zamanı (PT) ve pıhtı oluşumu measured automatically: clotting time (CT) and clot formation zamanı (CFT), ExTEM’de CT, CFT ve maksimum pıhtılaşma time (CFT) with intrinsic activation by tissue factor (InTEM), zamanı ve FibTEM'de MCF den oluşan thromboelastometri pa- CT, CFT and maximum clot firmness (MCF) with extrinsic acti- rametreleri otomatik olarak ölçüldü. vation by tissue factor (ExTEM) and MCF with FibTEM. Bulgular: ExTEM CT değerleri kontrol grubuna göre M/H Results: The ExTEM CT value was found to be significantly lon- grubunda önemli ölçüde daha yüksek bulundu. ExTEM CFT ger in the M/H group than in the controls. The ExTEM CFT medyan ve persentil değerleri şöyledir: C grubu 85S (70-95s), M median and percentile values were: group C: 85 s (70–95 s), group grubu 115s (94-128s), HS grubu 102S (84-114s), M/H grubu M: 115 s (94–128 s), group HS: 102 s (84–114 s), group M/H: 128S (110-144s), HS /H grubu 118S (107-132s). FibTEM MCF 128 s (110–144 s) and group HS/H: 118 s (107–132 s). In all the değerleri tüm gruplarda kontrol grubuna oranla anlamlı olarak groups, FibTEM MCF values were significantly lower than the düşük bulunmuştur. Grup M ile grup HS arasında anlamlı fark control and also there was a significant difference between groups mevcuttur. M and HS according to FibTEM MCF values. Sonuç: Her iki solüsyonda özellikle fibrin-fibrinojen etkileşimini Conclusion: Whole-blood coagulation disorder induced by these bozmaktadır. Fakat %3 NaCl'nin koagulasyon üzerine negatif et- solutions is mainly dependent on fibrinogen and fibrin interaction. kisi daha azdır. However, 3% HS has much less negative effect on coagulation. Anahtar Kelimeler: Nöroanestezi, %20 mannitol, %3 NaCl, ko- Keywords: 20% mannitol, 3% NaCl, coagulation, neuroanaesthesia agülasyon Introduction annitol and hypertonic saline (HS) are commonly used to reduce brain oedema and intracranial pressure and to minimise brain volume in neurosurgical practise (1). Mannitol is recommended as a first-choice hyperosmotic agent (2). However, clinical trials in recent years have shown that HS is at least as effective as, if not better than, M -1 mannitol in the treatment of intracranial hypertension (3, 4). Twenty per cent mannitol (1,098 mOsm L ) and 3% HS (1,024 mOsm L-1) are commonly used hyperosmotic fluids in our clinic, and many centres have found almost the same osmolarity at the same volume (5). Previous in vitro and clinical studies demonstrated that both fluids cause coagulation im- pairment (clot strength, disturbs fibrin formation and platelet function) and that the degree of coagulopathy increases linear- Address for Correspondence/Yazışma Adresi: İbrahim Özkan Akıncı E-mail: [email protected] Received / Geliş Tarihi : 02.10.2016 87 ©Copyright 2017 by Turkish Anaesthesiology and Intensive Care Society - Available online at www.jtaics.org ©Telif Hakkı 2017 Türk Anesteziyoloji ve Reanimasyon Derneği - Makale metnine www.jtaics.org web sayfasından ulaşılabilir. Accepted / Kabul Tarihi : 20.01.2017 Turk J Anaesthesiol Reanim 2017; 45: 87-92 ly with the amount of fluid used (6, 7). However, the studies Methods evaluated these hypertonic solutions separately and not with each other. In the literature, only one study has compared the Ethical approval for this study (Ethics Committee No. effect of mannitol and HS on coagulation (1). Luostarinen et 2014/1619) was provided by the Ethic Committee on 24 Oc- al. (1) investigated the effects of both fluids at doses higher tober 2014. The trial was conducted in accordance with guide- than used intraoperatively and did not consider the effects lines of the Helsinki Declaration on Human Subjects and of colloid addition. In cranial surgeries, mannitol 1 gr kg-1 was registered at anzctr.org.au (ACTRN12615000005550). (or less) and equivalent HS is used as an anti-oedematous Written informed consent was obtained from all volunteers. therapy. Colloid use can be necessary during neurosurgery Forty healthy volunteers aged between 18 and 65 years were because of bleeding and hypotension. Rapidly degradable hy- evaluated for inclusion in the study. Twenty-eight appropriate droxyethyl starch solutions (HES 130/0.4) also have negative volunteers were found, and of these 28, 15 were chosen using effects on coagulation (8). In the present study, we simulated closed-envelope selection. Inclusion criteria for the study were giving 5 mL kg-1 (1 gr kg-1) 20% mannitol and 3% HS to a no history of chronic or acute diseases (e.g. coagulation dis- healthy 70–80 kg patient in an in vitro environment for the order, renal or hepatic failure); no intake of any medication, first time. in particular acetylsalicylic acid or nonsteroidal anti-inflam- matory agents within 1 week of the study; no alcohol or drug The primary aim of the present study was to compare the abuse and smoking; and haematocrit (Hct), activated partial effect of 20% mannitol with 3% HS on blood coagulation in thromboplastin time (aPTT), international normalised ratio vitro using rotational thromboelastometry (ROTEM). Addi- (INR) and platelet values within the normal range (Figure 1). tionally, we investigated the effect of adding HES 130/0.4 to The demographic characteristics of the volunteers who were these hypertonic solutions on blood coagulation. included in the study were recorded. Assessed for eligibility (n=40) Excluded (n=12) Not meeting inclusion criteria (n=10) Enrollhent Declined to participate (n=2) Eligible patiens (n=28) Closed envelope drawing Randomized (n=15) (Crossover study) Group I Group II Group III Group IV Group V (Control) (7% Mannitol) (7% HS) (6% Mannitol-8%HES) (6% HS-8%HES) (n=15) (n=15) (n=15) (n=15) (n=15) Allocation Discontinued Discontinued Discontinued Discontinued Discontinued intervention intervention intervention intervention intervention (n=0) (n=0) (n=0) (n=0) (n=0) Follow-Up Analysed Analysed Analysed Analysed Analysed (n=15) (n=15) (n=15) (n=15) (n=15) Analysis Figure 1. Flow chart of the study 88 Ali et al. Hypertonic Fluids and Coagulation Randomisation and blinding 2 Blood samples were taken from 15 volunteers by the first re- 1.14 1.14 1.16 1.16 searcher in a random order that was determined in a draw. 1.8 0.12 0.12 Test solutions were added to the blood samples by the first 1.6 HES 130/0.4 mL 3% NACL mL mL 2 researcher and the samples were coded. The second researcher 20% mannitol mL 1.4 1.86 1.86 made the thromboelastometric analysis, but he/she did not 1.72 1.72 Blood mL know to which group and volunteer the blood samples be- 1.2 longed. At the end of the research, the two researchers com- 1 pared their data. Group C Group M Group HS Group M/H Group HS/H Trial method Figure 2. Composition of dilutions Twenty-millilitre blood samples were obtained from an an- TM tecubital vein using an 18-G venous cannula (Vasofix , and clot formation time (CFT) with InTEM; CT, CFT and B. Braun, Melsungen, Germany) from each participant. maximum clot firmness (MCF) with ExTEM and MCF with Four-millilitre blood samples were separated for each group. FibTEM. Moreover, the samples in the EDTA tubes were In each group, 2 mL of blood was collected into polypro- mixed with the test solutions, and haemoglobin (Hb) con- pylene tubes (Vacuette, Greiner Bio-one, Austria) contain- centration, haematocrit value (Hct) and platelet count (Pc) ing 3.2% buffered citrate, giving a volume ratio of 1:10 for were determined for each group using a Cell-Dyn 610 He- ROTEM analysis, and 2 mL blood was collected into EDTA matology Analyzer (Sequoia-Turner Corporation, Mountain tubes containing 1.2 mg anhydrous EDTA per 1 mL blood View, CA, USA).