International Journal of Science and Research (IJSR) ISSN (Online): 2319-7064 Impact Factor (2012): 3.358 A Pilot Study to Compare Effects of Mannitol with Hypertonic Saline in Combination with HES on Blood Coagulation and Platelet Function during Elective Craniotomy Vidhu Bhatnagar INHS Asvini, Mumbai, India Abstract: Neurosurgery requires the use of osmotic agents to reduce intracranial pressure which can adversely affect coagulation. Thromboelastography provides early indicator of derangement of coagulation. A prospective, non randomized pilot study was conducted to compare the effect of administration of either mannitol or hypertonic saline and when combined with hydroxy ethyl starch on coagulation and platelet function, as measured by Thromboelastography. 22 neurosurgical patients, divided into 2 groups, received 20% mannitol (n=12) or 3% hypertonic saline (n = 10) followed by administration of hydroxy ethyl starch (HES). The Thromboelastography parameters were comparable in both the groups at baseline; after administration of the drug and also after HES administration. The results show that combining a single dose of either mannitol or hypertonic saline with hydroxyl ethyl starch does not appear to affect in-vivo coagulation. Keywords: 1) Mannitol; 2) Saline solution, Hypertonic; 3) Hydroxyethyl starch; 4) Thromboelastography; 5) Coagulation 1. Introduction morbid illness or with well controlled co-morbid illnesses) between 18-65 years posted for elective One of the important goals of anaesthetic management for decompression/resection of tumours with preoperative patients undergoing craniotomy is to provide a relaxed Glasgow coma scale (GCS) 15 were recruited. Pregnant brain for the surgeon to operate on. This allows easy women, paediatric or geriatric age group patients, persons surgical manipulations and causes less damage to the incompetent to give informed consent or prisoners were not normal brain tissue. This in turn, results in less secondary recruited for the study. Patients with known allergy to injury to the brain, which improves the patient's neurologic mannitol or HS or HES, or with compromised outcome. Therefore, elective neurosurgical procedures cardiovascular status or Diabetes mellitus and patients who often require the use of osmotic agents such as mannitol or had history of prolonged anti epileptic drug (AED) hypertonic saline (HS) to reduce intracranial pressure by ingestion were also excluded, on account of the effects of reducing the brain bulk1, 2, 3. Some tumours in the brain AEDs and prolonged deranged glycaemic control on the such as meningiomas can result in considerable blood loss platelet functions. Informed consent was duly obtained. during surgery due to their high vascularity. Intravascular volume resuscitation in these situations is done with the Patients were divided into two groups, first group received help of crystalloids and colloids. Consequently, such 20% mannitol with a dosage of 1 gram/kg body weight, on patients who have received Mannitol or Hypertonic Saline beginning of craniotomy, followed by administration of are administered colloids such as Hydroxy ethyl starch. HES. The other group received 3% hypertonic saline with a Mannitol, Hypertonic saline and Colloids, such as Hydroxy dosage of 5 ml/kg body weight, on beginning of ethyl starch, interfere with coagulation of blood and are craniotomy, followed by administration of HES. known to cause defects in coagulation. This pilot study was Monitoring for haemodynamics, oxygentation and carried out to compare the effects of administration of ventilation was done intraoperatively. A standardized either mannitol or HS as well as when these two agents are general anaesthesia technique consisting of induction with combined with HES on in-vivo blood coagulation and propofol and fentanyl, tracheal intubation after muscle platelet function in patients undergoing elective relaxation with Vecuronium and maintenance of neurosurgical procedures using Thromboelastography anaesthesia with air, oxygen and sevoflurane/isoflurane (TEG)4. (MAC 0.6-0.8) was followed in all patients. Requirement of fluids was calculated to maintain pulse pressure variation (PPV). 2. Methods Permission for carrying out the study from Institutional Baseline investigations such as Haemoglobin (Hb), Ethics Committee was obtained. 22 patients, divided into 2 platelet count, Prothrombin Time (PT), Activated groups (10 studied in HS group and 12 studied in mannitol Prothrombin Time (APTT) and platelet function test (by group), who were subjected to elective decompression/ Thromboelastograph coagulation analysers (TEGR 5000 resection of tumours were recruited in the pilot study. Haemostasis Analyser System) were done in all patients Adult males or females in American Society of before the start of surgery. A second set of similar Anaesthesiology grade (ASA) I or II (patients with no co- investigations namely Hb, platelet count, PT, APTT and Volume 3 Issue 12, December 2014 www.ijsr.net Paper ID: SUB14622 Licensed Under Creative Commons Attribution CC BY 1115 International Journal of Science and Research (IJSR) ISSN (Online): 2319-7064 Impact Factor (2012): 3.358 platelet function test (by TEG) were performed 15 minutes The secondary end points (Table 3) analyzed were the after the administration of mannitol or hypertonic saline, as mean intra operative consumption of crystalloids, colloids, Mannitol and HS take 10 – 30 minutes to show their Fresh Frozen Plasma (FFP) and Packed Red Blood Cells osmotic action. Thereafter, both groups of patients received (PRBC). The mean intra operative consumption of 20ml/kg of HES (Voluven® - Fresenius Kabi, Bad crystalloids was 2535 ml (±1562.1 ml) in the HS group Homburg, Germany - consisting of a maize derived 6% whereas it was 3318.2 ml (±1209.8 ml) in the mannitol HES of Molecular weight130 kDa, Molar Substitution group. The p value for this distribution was 0.219. The 0.40, C2/C6 ratio 9:1 and suspended in normal saline) and mean intraoperative consumption of colloids was 1050 ml the next set of similar investigations Hb, platelet count, PT, (±158.1 ml) in the HS group whereas it was 1218 ml APTT and platelet function test (by TEG) were repeated in (±252.3 ml) in the mannitol group. The p value for this both the groups, 15 minutes after the administration of distribution was 0.086. The mean intraoperative HES, for the haemodilution to take place. Primary end consumption of FFP was 0.3 Units (±0.7 Units) in the HS points studied were: Hb, PT, and APTT, Platelet function group whereas it was 0.36 Units (±1.2 Units) in the test assessed by TEG and platelet count at three points as Mannitol group. The p value for this distribution was already notified. Secondary end points noted were: total 0.885. The mean intraoperative consumption of PRBC was amounts of crystalloid, colloid, bleeding, urine output and 0.9 Units (±1.5 Units) in the HS group whereas it was 1.36 blood and blood products used during surgery. Units (±1.9 Units) in the mannitol group. The p value for Postoperative CT was not undertaken routinely to rule out this distribution was 0.535. any haematoma. 4. Discussion Data was analyzed using SPSS software. Two way repeated measure Anova was utilized to find out any In this prospective pilot study to understand the effects of significant difference between different time points. If a combining mannitol or HS with HES on coagulation, we statistical difference was found then post hoc analysis did not observe any statistically significant changes applying Bonferroni test was done to know which time between the two groups. There was no difference in points differed statistically. Continuous data was compared baseline coagulation status in patients with gliomas and with independent t test between the two groups. meningiomas. We also analyzed coagulation changes within the same group (within group analysis) as compared 3. Results to baseline. We did not observe any clinically and statistically significant changes in TEG parameters. The age of patients in both the HS and the mannitol groups were comparable with mean age being 45 (±9.7) and 40.8 Mannitol or HS are administered in the setting of (±11.4) years respectively. Males and Females were neurosurgery for providing a relaxed brain5. This study was equally distributed in both the groups being 50% each. conducted to objectively delineate the effects of Mannitol and HS on blood coagulation when used along with HES in The distribution of various type of tumours were: patients undergoing elective craniotomy, by Vestibular Schwannomma (9); Glioma (3); Meningioma Thromboelastography. (5); Pituitary Macroadenoma (1); Craniopharyngioma (2); Epidermoid tumour (1) and Hemangiopericytoma (1). Thromboelastography is a more sensitive test of fibrinolytic activity than conventional measurements of Hb (in gm %), PCV, PT, APTT, Platelet Count was fibrin degradation products. Four values that represent clot comparable in both the groups at baseline. The TEG formation are determined by this test: the R value (or parameters like the R value, K value, Alpha (α) angle and reaction time), the K value, the angle and the MA Maximum Amplitude (MA) values were also comparable (maximum amplitude). The R value represents the time in both the groups at baseline. Within group comparison until the first evidence of a clot is detected. The K value is Hb, PCV showed a statistically and clinically significant the time from the end of R until the clot reaches 20mm and decline (Table 1). However, these differences were similar this represents the speed of clot formation. The alpha angle in both the groups. The change in R value and K value was is the tangent of the curve made as the K is reached and not statistically significant, both within as well as between offers similar information to K. The MA is a reflection of group comparisons (Table 1). The changes in the alpha clot strength. angle were similar in both the groups and were maintained within normal limits at all times. The change in MA value In various in-vitro studies, mannitol has been found to alter was not statistically significant both, within as well as the coagulation parameters such as, clotting time, clot between group comparisons (Table 1).