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Year : 2000  |  Volume : 48  |  Issue : 1  |  Page : 63-7

Safety of acute normovolemic haemodilution with hydroxyethyl starch during intracranial surgery.

Department of Neuroanaesthesia, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.

Correspondence Address:
Department of Neuroanaesthesia, National Institute of Mental Health and Neurosciences, Bangalore, 560029, India.

  »  Abstract

The effect of acute normovolemic haemodilution on haemodynamics, serum osmolality and coagulation parameters was studied in 20 patients undergoing intracranial surgical procedures. After induction of anaesthesia, 740+/-153 ml of blood was collected and the same was replaced with an equal volume of 6% hexaethyl starch. Heart rate (HR), blood pressure (BP), central venous pressure (CVP) and end tidal carbon dioxide tension (Et CO2) were monitored for 45 min. Haemoglobin concentration (Hb), haematocrit (Hct), serum osmolality (Osm), bleeding time (BT), prothrombin time (PT) and platelet count were determined before and 45 min after haemodilution. Hb and Hct were significantly lower following haemodilution (13.1+/-1.8 and 10.3+/-1.7 g/dL for Hb and 38.0+/-4.6%. and 30.1+/-4.5% for Hct). There was no significant change in the HR, BP and Et CO2 throughout the study period. CVP increased marginally from 35 to 45 min but was within normal limits. There was no significant change in serum osmolality, bleeding time and prothrombin time following haemodilution. Platelet count decreased following haemodilution but the values were within normal limits. The brain relaxation, as assessed by a semiquantitative scale, was satisfactory in all cases. None of the patients developed intraoperative brain swelling. In conclusion, acute normovolemic haemodilution with hexaethyl starch is tolerated well haemodynamically. It does not cause changes in serum osmolality which can increase brain oedema. It has no adverse effect on intraoperative haemostasis. It is a safe technique to decrease homologous blood transfusion during intracranial surgery.

How to cite this article:
Kiran Prasad K M, Devaragudi T S, Christopher R, Chandramouli B A, Umamaheswara Rao G S. Safety of acute normovolemic haemodilution with hydroxyethyl starch during intracranial surgery. Neurol India 2000;48:63

How to cite this URL:
Kiran Prasad K M, Devaragudi T S, Christopher R, Chandramouli B A, Umamaheswara Rao G S. Safety of acute normovolemic haemodilution with hydroxyethyl starch during intracranial surgery. Neurol India [serial online] 2000 [cited 2020 Dec 5];48:63. Available from:

   »   Introduction Top

Increased awareness of risks related to homologous blood transfusions such as immunological reactions,[1] transmission of infections.[2],[3],[4] and immunosuppression[5] has necessitated exploration of alternative techniques to deal with the needs of intraoperative blood transfusion. Acute normovolemic haemodilution is one such technique. Though this technique is commonly employed in other types of surgery, there is a hesitation to implement this bloodsalvaging strategy in patients undergoing intracranial surgery. Two main concerns that have discouraged its
usage in neurosurgical patients are:- (i) the possibility of enhanced brain oedema resulting from haemodilution and (ii) increased risk of bleeding due to dilution of clotting factors. Serum osmolality and oncotic pressure changes are major determinants of brain oedema formation in patients with intracranial lesions.[6],[7] The risk of exaggeration of brain oedema will be eliminated during haemodilution, if the osmolar and oncotic changes due to the procedure are minimised. Hexaethyl starch (HES) is a plasma volume substitute with a wide range of macromolecules with molecular weights ranging from 30,000 to 2,400,000 daltons. Dispensed as a 6% solution in a balanced electrolyte solution, it has an osmolality of 308 mosm/kg. We propose that using 6% hexaethyl starch solution in an isotonic electrolyte solution should not cause any change in either the plasma osmotic or oncotic pressures and as such should not have any effect on brain oedema. Concerns have been expressed earlier with regard to the anticoagulant effects of hexaethyl starch in healthy volunteers,[8],[9] and neurosurgical patients.[10],[11]
In this study, we tried to evaluate the safety of acute normovolemic haemodilution with a 6% hexaethyl starch in a group of neurosurgical patients undergoing intracranial surgery. We studied the effect of this technique on haemodynamics, serum osmolality, bleeding time, prothrombin time and platelet count. In addition, we also assessed the condition of brain at surgery and any other adverse intraoperative or immediate postoperative effects of the technique.

   »   Materials and methods Top

Twenty neurosurgical patients undergoing various elective intracranial procedures listed in [Table I] were included in the study. Inclusion criteria were age < 60 years and > 12 years, haemoglobin concentration > 12 g/dL. Patients with associated cardiorespiratory diseases, those who had major fluid and electrolyte disturbances and those who had received any osmotic diuretics such as mannitol and glycerol within 12 hours of the study were not included in the study. None of the patients had history of any coagulation disorder. At surgery, anaesthesia was induced with morphine 0.1mg/kg bodyweight and thiopentone 5-7mg/kg. Endotracheal intubation was carried out following muscle relaxation with 0.1mg/kg of pancuronium bromide. Anaesthesia was maintained by intermittent positive pressure ventilation with nitrous oxide and oxygen (60:40) and halothane 0.5% delivered by a Siemen's Servo 900 D ventilator. Central venous and arterial lines and two large bore peripheral intravenous lines were established following induction. Direct arterial blood pressure, central venous pressure, ECG, pulse oximetry and endtidal carbon dioxide were monitored throughout the procedure by a Datex Cardiocap II (Datex Instrumentaruim, Finland) multiparameter monitor. After stabilisation of anaesthesia, blood samples were collected for measurement of haemoglobin, haematocrit and serum osmolality in all patients. Bleeding time was assessed by pin-prick method. Prothrombin time was measured in 11 patients.
Technique of Haemodilution: After recording the baseline cardiorespiratory parameters i.e. heart rate (HR), systolic (SBP), diastolic (DBP) and mean arterial pressures, (MAP) central venous pressure [CVP], oxygen saturation [SaO2] and endtidal carbon dioxide tension (Et CO2), blood was drawn from one of the peripheral intravenous lines into a 400 ml blood collection bag with 63 ml of citrate-phosphate-dextrose-adenine (CPDA) medium. Simultaneously, hexaethyl starch was infused from another peripheral intravenous line. The rate of administration of HES was adjusted to match the rate of collection of the blood. It was aimed to collect an approximate volume of 700 ml of blood from each patient. The quantity of blood salvaged was replaced with equal volume of HES. HR, SBP, DBP, MAP, CVP, SaO2 and EtCO2 were monitored every 5 min up to 45 min from the commencement of haemodilution. At the end of 45 min, blood samples were collected for measurement of haemoglobin, haematocrit and serum osmolality in all patients and prothrombin time in 11 patients. Bleeding time was also determined in all patients at the end of 45 min. Serum osmolality estimations were made by freezing point depression technique using an automated cryoscopic osmometer (Osmomat 030 N, Gonotec GmBH, Germany). The Quick's one-stage prothrombin time test was performed by adding tissue thromboplastin to plasma and estimating the time required for formation of clot which was detected by the tilt-tube technique.
Surgical procedures continued following haemodilution. Brain relaxation was recorded at the time of dural opening on a scale of 1 to 4 (brain bulging above the level of craniotomy margin corresponding to Grade 1 and brain surface well below the craniotomy margin corresponding to Grade 4). Intraoperative blood loss was replaced with the salvaged blood. The last unit collected was replaced first. Homologous blood was transfused if the blood loss exceeded the volume of salvaged blood. Any fresh neurological deficits diagnosed by the operating surgeon at the end of the surgery were noted down. Haemoglobin, haematocrit, prothrombin time and bleeding time were estimated twenty four hours following the surgery.
Statistics: Haemoglobin, haematocrit, serum osmolality, bleeding time prothrombin time before and after haemodilution were compared by Student's 't' test. HR, SBP, DBP, MAP, CVP and Et CO2 values recorded at 5 min intervals for 45 min were compared by analysis of variance for repeated measures. All data are expressed as mean ± standard deviation. SPSS Release 6.0 statistical package (SPSS Inc.) was used to perform the statistical analysis. 'p' value of less than 0.05 was considered as significant.

   »   Results Top

There were 20 patients in the study (Mean age: 41.6±11.5; Sex: Male:Female = 12:8; Preoperative GCS of 15). Eighteen patients were in ASA Grade 1. Two patients were in ASA Grade 2. Preoperative blood glucose, urea, creatinine, serum sodium and potassium were within normal limits in all the patients. Mean haemoglobin and haematocrit levels before haemodilution were 13.1±1.8 g/dL and 38.0±.4.6% respectively. Mean haemoglobin and haematocrit following haemodilution were 10.3±1.7 g/dL and 30.1±4.5%. A mean volume of 740±153 ml of blood was collected from all the patients. Intraoperative blood loss was replaced only by salvaged blood in 18 patients. Homologous transfusions of 700 and 600 ml were required in addition to replacement of salvaged blood only in two patients.
Haemodynamic parameters during the first 45 min from the commencement of the procedure are shown in [Figure. 1]. There was no significant change in the HR, SBP, DBP, MAP. Central venous pressure was marginally higher than the baseline value from 35 min till the end of 45 min (p < 0.05). [Figure. 2] shows the serum osmolality values before and at 45 min. There was no statistically significant difference in the serum osmolality values before and after haemodilution (312±18 vs 314+27 mosm/kg). There was no significant difference in prothrombin time before and after haemodilution in 11 the patients in whom it was measured (96±10% vs 107±19% of control). Platelet count at 45 min was lower than the baseline value (2.66+0.65 to 2.22+0.64). But the counts were within clinically acceptable levels so as not to affect the coagulation. Intraoperatively, all patients had a brain laxity of Grade 3 and 4. In none of the patients surgery was rendered difficult by tense brain. Two patients experienced intraoperative complication unrelated to haemodilution. One patient had moderate hypotension soon after anaesthetic induction even before commencement of haemodilution, which was resuscitated with intravenous fluids. Once the blood pressure was restored, haemodilution proceeded uneventfully. Another patient had a persistent bradycardia due to beta blockers administered preoperatively. Postoperatively, all patients were awake and had a GCS of 15. Haemoglobin concentration and haematocrit on the first postoperative day were 10.97±1.62g/dL and 32.28±4.81% respectively.

   »   Discussion Top

Scarcity of banked blood and risks of homologous transfusion have necessitated search for blood salvaging techniques in recent years. Acute normovolemic haemodilution is a simple and easy technique of replacing intraoperative blood loss with the patient's own blood. This technique is used more widely in other types of surgery as compared to neurosurgery. Despite the fact that elective neurosurgical patients are most often otherwise healthy and are fit candidates for acute normovolemic haemodilution, the technique is not widely practised. Considerations related to changes in serum osmolality and oncotic pressure and consequent increase in brain oedema and also the possibility of interference with haemostatic mechanisms due to dilution of coagulation factors seem to be the underlying factors for such hesitation in using this technique regularly. In the present study we provide evidence to show that neither of these problems occurs when intraoperative isovolemic haemodilution is employed in elective neurosurgical procedures.
Oncotic and osmotic pressure Changes in the aggravation of brain oedema: Earlier experimental studies have documented that even a 4-5% reduction of serum osmolality can increase brain water content significantly.[6] Taking into account the evidence that maintaining serum osmolality is essential to prevent an increase in brain oedema, during acute normovolemic haemodilution, it is mandatory that the solution used for replacement be isotonic. The composition of the HES solution used in the study is shown in table II. The osmolality of the solution was 308 mosm/kg, which is unlikely to cause any reduction in the serum osmolality. There was amply borne out by the pre and post-dilutional serum osmolality values in the present study. Isotonic crystalloid solutions such as 0.9% saline could have been used without the risk of decreasing the serum osmolality. But such a technique requires usage of large volumes crystalloid (at least 2-3 times the volume of blood salvaged) to maintain normal intravascular volume which, in turn, would result in extracellular oedema. In a recent experimental study of acute isovolemic haemodilution,[7] replacement of shed volume by saline (twice the volume of shed blood) was associated with higher brain water content than replacement with 6% hexaethyl staech, both in the normal as well as injured brain. These results point to the fact that colloid oncotic pressure is also an important determinant of the formation of oedema. So, a colloid in isotonic salt solution would cause the lowest risk of aggravation of brain oedema during haemodilution. HES used in this study conforms to this requirement. All patients in the study had a good brain laxity at surgery indicating that haemodilution did not aggravate formation of brain oedema. The procedure did not cause any significant cardiovascular changes which could have aggravated brain oedema. It did not produce any significant change in the serum osmolality. Colloid oncotic pressure is unlikely to have changed as the salvaged blood volume has been replaced by a colloid with a molecular weight of 450,000.
A reduction of haematocrit during haemodilution may bring about changes in cerebral blood flow (CBF). That such changes in CBF do not affect the intracranial pressure has been documented in one of the recent studies utilising a similar technique of haemodilution with 6% HES. In that study there was an increase in middle cerebral artery blood flow velocities, without any significant change in cerebrospinal fluid pressure.[12] A recent study[13] has also indicated that HES attenuates blood-brain-barrier (BBB) disruption caused by intracarotid injection of hyperosmolar mannitol in rats indicating the protective effect of HES on BBB at risk of disruption. On the whole, the procedure does not have any significant effect on intraoperative brain oedema.
Effect of Haemodilution on Haemodynamics: HR, SBP, DBP, MAP and Et CO2 were not significantly altered by haemodilution which indicates that the procedure, as it has been carried out in this study, is very well tolerated haemodynamically. The only haemodynamic parameter that changed marginally following haemodilution was the central venous pressure. This increase (from 5.32+2.40 to 7.30±3.70 mmHg) occurred despite replacement of hexastarch in volumes equal to the salvaged blood. One probable reason for this may be the fact that every unit of 6% hexaethyl starch transfused attracts 1.2 units of water from the extracellular fluid into the intravascular compartment. Despite an elevation, the absolute value of CVP still remained well within physiological range that does not pose any threat of increasing the brain oedema.
Effect of Haemodilution on Haemostasis: Contrary to the widely held concern that haemodilution may enhance the risk of bleeding due to dilution of the coagulation factors,[8],[9],[10],[11],[14] there is substantial evidence to show that the technique actually has a procoagulant effect.[15] This increase in the coagulability of blood seems to be more pronounced when crystalloids are used for haemodilution and the hypercoagulability has been reported to be partly offset by HES through its antiplatelet action.[16] On the whole, haemodilution with HES does not seem to carry any added risk of enhanced bleeding at surgery. In the present study, in eleven patients in whom prothrombin time was studied, its value did not change significantly following haemodilution. There was also no significant difference between pre- and post-dilutional bleeding times. The platelet count was significantly lower following haemodilution. This can be expected to be a result of the dilutional effect of the technique. But restricting the volume of haemodilution to two units as in this study would still keep the absolute platelet count within physiologically acceptable range so that thrombocytopaenia does not pose any additional risk.
In conclusion, acute normovolemic haemodilution with 6% HES is a safe procedure of blood conservation in neurosurgical patients undergoing intracranial operations. It is very well tolerated haemodynamically. It does not cause any haemodynamic and osmolar changes which are likely to enhance the risk of brain oedema. It does not have any adverse effect on haemostatic mechanisms that could enhance the risk of bleeding at surgery.


  »   References Top

1.Hogman CF: Immunologic transfusion reactions. Acta Anaesthesiol Scand 1988; 32: S4-12.   Back to cited text no. 1    
2.Hoofnagle JH: Post transfusion hepatitis B. Transfusion 1990; 30: 384-386.   Back to cited text no. 2    
3.Trepanier CA: Transmission of hepatitis and AIDS; risks for the anaesthetists and the patient. Can J Anaesth 1991; 38: R102-104.  Back to cited text no. 3    
4.Ward JW, Holmberg SD, Allen JR et al: Transmission of human immunodeficiency virus (HIV) by blood transfusions screened as negative for HIV antibody. N Engl J Med 1988; 318: 473-478.   Back to cited text no. 4    
5.Messmer K: Haemodilution - possibilities and safety aspects. Acta Anaesthesiologica Scand 1988; 30: 49-53.   Back to cited text no. 5    
6.Zornow MH, Todd MM, Moore SS: The acute cerebral effects of changes in plasma osmolality and oncotic pressure. Anesthesiology 1987; 67: 936-941.   Back to cited text no. 6    
7.Drummond JC, Patel PM, Cole DJ et al: The effect of the reduction of colloid oncotic pressure, with and without reduction of osmolality, on post-traumatic cerebral oedema. Anesthesiology 1998; 88: 993-1002.   Back to cited text no. 7    
8.Stump DC, Strauss RG, Henriksen RA et al: Effects of hydroxyethyl starch on blood coagulation, particularly factor VIII. Transfusion 1985; 25: 349-354.   Back to cited text no. 8    
9.Strauss RG, Stump DC, Henriksen RA et al: Effects of hydroxyethyl starch on fibrinogen, fibrin clot formation and fibrinolysis. Transfusion 1985; 25: 230-234.   Back to cited text no. 9    
10.Symington BE: Hertastarch and bleeding complications. Ann Inten Med 1986; 105: 627-628.   Back to cited text no. 10    
11.Damon L, Adams M, Stricker RB: Intracranial bleeding during treatment with hydroxyethyl starch. New Engl J Med 1987; 317: 964-965.   Back to cited text no. 11    
12.Bruder N, Cohen B, Pellissier D et al: The effect of haemodilution on cerebral blood flow velocity in anaesthetised patients. Anesth Analg 1998; 86: 320-324.   Back to cited text no. 12    
13.Chi OZ, Lu X, Wei HM et al: Hydroxyethyl Solution attenuates blood brain barrier disruption caused by intracarotid injection of hyperosmolar mannitol in rats. Anesth Analg 1996; 83: 336-341.   Back to cited text no. 13    
14.Claes Y, Hemelrijck JV, Gerven HV et al: Influence of hydroxyethyl starch on coagulation in patients during the post operative period. Anaesth Analg 1992; 75: 24-30.   Back to cited text no. 14    
15.Ruttmann TG, James MFM, Viljoen JF: Haemodilution induces a hypercoagulable state. Brit J Anaesth 1996; 76: 412-414.   Back to cited text no. 15    
16.Ruttmann TG, James MFM, Aronson L: In vivo investigation into the effects of haemodilution with hydroxyethyl starch and normal saline on coagulation. Brit J Anaesth 1998; 80: 612-616.   Back to cited text no. 16    


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