Stroke volume-directed administration of hydroxyethyl starch or Ringer's acetate in sitting position during craniotomy.

BACKGROUND: To determine the volumes required for stable haemodynamics and possible effects on the coagulation, we studied stroke volume (SV)-directed administration of hydroxyethyl starch (HES 130 kDa/0.4) and Ringer's acetate (RAC) in neurosurgical patients operated on in a sitting position. METHODS: Thirty craniotomy patients were randomised to receive either HES or RAC. Before positioning, SV, measured by arterial pressure waveform analysis, was maximised by boluses of fluid until SV did not increase more than 10%. SV was maintained by repeated administration of fluid. RAC 3 ml/kg/h was infused in both groups during surgery. RESULTS: Comparable haemodynamics were achieved with the mean [standard deviation (SD)] cumulative doses of HES or RAC 271 (47) or 264 (50) ml (P = 0.699) before the sitting position. Mean (SD) doses of HES or RAC at 30 min after the positioning were 343 (94) or 450 (156) ml (P = 0.036), and at the end of surgery 464 (284) or 707 (425) ml, respectively (P = 0.087). The intraoperative fluid balance was more positive in the RAC than in the HES group [P = 0.044, 95% confidence interval (CI) -978 to -14]. Cardiac and stroke volume indexes [CI and stroke volume index (SVI)] increased in the HES group (P < 0.05) but not in the RAC group [non significant (N.S.)]. Neither coagulation profile nor blood loss differed between the groups. CONCLUSION: Fluid filling with HES boluses resulted in a positive response in CI and SVI during the sitting position. The 34% smaller volume of HES than crystalloid and less positive fluid balance in the HES group might be important in craniotomy patients with decreased brain compliance.

Effects of combined balanced colloid and crystalloid on rotational thromboelastometry in vitro.

Our objective was to investigate the in vitro effects of a totally balanced fluid concept on whole blood coagulation. Venous blood from 12 healthy volunteers was diluted by 20% and 40% with a combination of an equal amount of colloid (balanced or unbalanced 6% HES 130/0.4, or 4% gelatin) and crystalloid (balanced or unbalanced Ringer's acetate). Blood samples were analyzed with rotational thromboelastometry (ROTEM®). The initiation of coagulation was delayed in all dilutions except for the 20 vol% gelatin-dilution. In the extrinsic activation test, maximum clot firmness was decreased and clot formation time prolonged after 40 vol% hemodilution with a balanced Ringer's/unbalanced HES combination, more than in the corresponding gelatin hemodilution. In the fibrin-based test, after both 20- and 40 vol% hemodilution with unbalanced Ringer's/gelatin solution, maximum clot firmness was significantly stronger than in the Ringer's/HES-combinations. The combination of balanced colloid and crystalloid has similar coagulation effects in vitro as their respective combination of unbalanced solutions.

Role of fibrinogen-, factor VIII- and XIII-mediated clot propagation in gelatin haemodilution.

BACKGROUND: Gelatin solution impairs coagulation. The mechanism of coagulopathy is incompletely defined. The purpose of this study was to evaluate the capacity of single coagulation factors to reverse gelatin-promoted whole-blood coagulation disorders in vitro. METHODS: Venous blood was withdrawn from 12 volunteers in a crossover study. Four percent succinylated gelatin was added to citrated whole-blood samples to make a 40 vol% end-concentration of gelatin. The baseline and 40 vol% samples, and samples with addition of fresh-frozen plasma (FFP), fibrinogen, coagulation factors XIII (FXIII) or VIII, together with the von Willebrand factor (FVIII+vWF), were analysed by thromboelastometry (ROTEM. Coagulation was initiated by tissue thromboplastin (ExTEM with and without cytochalasin to determine the functional component of fibrinogen (FibTEM. RESULTS: Initiation of coagulation and fibrin formation were delayed at 40 vol% gelatin dilution. At this stage, the median (25th-75th percentiles) maximum clot firmness (MCF) was 76.3 (65.9-80.0) and 32.5 (27.4-45.0)% of the pre-dilution value in ExTEM and FibTEM thromboelastometry, respectively. Coagulation time was corrected by addition of fibrinogen and FFP in ExTEM and FibTEM analysis, whereas FVIII or FXIII had minimal effects. MCF was partly restored only by FFP in ExTEM. In FibTEM analysis, MCF improved more by fibrinogen than by FVIII+VWF, FXIII or FFP. CONCLUSIONS: Gelatin-induced whole-blood coagulation disorder in vitro is mainly dependent on the initial fibrinogen-fibrin interaction. The proposed mechanism might suggest not to reverse gelatin coagulopathy solely by fibrinogen administration. The administration of FFP, a mixture of different coagulation factors, reversed the gelatin-induced in vitro coagulopathy the best.

Whole blood hypercoagulability despite anticoagulation during mechanical cardiac assist.

We report hypercoagulability despite activated partial thromboplastin time (APTT)-guided heparin treatment during Berlin Heart-supported circulation in a 38-year-old man with heart failure for 19 days. The patient was anticoagulated using unfractionated heparin, acetylsalicylic acid and dipyridamole. Contact and tissue factor-activated thromboelastometry revealed increased clot firmness, although anticoagulation assessed by APTT was in accordance with the treatment protocol. Strength of polymerized fibrin was also increased. We saw no clinical signs of thrombosis. Thromboelastometry normalized after heart transplantation. Our results suggest that hypercoagulability is due to excess fibrin formation. Monitoring anticoagulation using APTT may, therefore, be misleading during mechanical cardiac assist.

Continuous spinal microcatheter (28 gauge) technique for arterial bypass surgery of the lower extremities and comparison of ropivacaine with or without morphine for postoperative analgesia.

BACKGROUND: The aim of this study was to evaluate a microcatheter technique for continuous spinal anaesthesia (CSA) and continuous spinal postoperative analgesia (CSPA) in vascular surgery. METHODS: A total of 47 patients (range 51-95 yr, ASA II-IV) undergoing peripheral bypass surgery of the lower extremities received a spinal microcatheter (28 gauge) at L3-L4 or L2-L3. For CSA, ropivacaine 7.5 mg ml(-1) was given in small increments. Central venous pressure was maintained >or=3 mm Hg. Of 47 patients, 44 received CSPA, either using ropivacaine alone 2 mg h(-1) (group R, n=22) or ropivacaine 1 mg h(-1) with morphine 8 microg h(-1) (group RM, n=22) for 24 h after surgery (randomized, double-blinded). RESULTS: Intraoperative haemodynamic control was good; during the initial 60 min only four patients received phenylephrine i.v. for hypotension. Up to 30% of the patients felt mild pain at incision but surgery [mean duration 173 min (range 66-327)] was successfully completed under CSA in 45 patients. In four instances of acute revision surgery, a new block was administered utilizing the spinal catheter in place. Postoperative pain relief was comparably adequate in both groups with no difference in rescue pain medication. Four patients (three in R, one in RM) had weak motor blockade in the first postoperative morning. CONCLUSIONS: The described CSA technique offered good haemodynamic control, ease of maintaining spinal anaesthesia, and ease of providing a new spinal block for revision. The combination of low-dose ropivacaine and morphine for CSPA did not offer any benefit compared with the higher ropivacaine dose alone.

Influence on platelet aggregation of i.v. parecoxib and acetaminophen in healthy volunteers.

BACKGROUND: Acetaminophen (paracetamol) alone or in combination with other analgesics is widely used for postoperative analgesia. While acetaminophen and non-steroidal anti-inflammatory drugs inhibit platelet function, the cyclooxygenase-2 (COX-2) selectively inhibiting coxibs show no interference with platelet function. The authors studied the effect of a combination of i.v. parecoxib and acetaminophen on platelet function in healthy volunteers. METHODS: Eighteen healthy, male volunteers (22-33 yr) received i.v. acetaminophen 1 g, parecoxib 40 mg+acetaminophen 1 g or placebo in a double-blind, crossover study. Platelet function was assessed by photometric aggregometry and by measuring the release of thromboxane B(2). Plasma acetaminophen concentrations were measured by high-performance liquid chromatography. RESULTS: Platelet aggregation (median area under the curve) triggered with arachidonic acid 500 microM was 24.6, 3.9 and 4.2x10(3) area units (P=0.02, all groups) after placebo, acetaminophen and parecoxib+acetaminophen, respectively. Inhibition of platelet aggregation showed no difference between acetaminophen alone and the combination (P=0.82). Aggregation triggered with arachidonic acid 750 or 1000 microM, adenosine diphosphate (ADP) 1.5 or 3 microM, or epinephrine 5 microM showed no differences between the groups. Release of thromboxane B(2) in response to ADP was inhibited similarly by both acetaminophen and the combination. Plasma acetaminophen concentrations were similar after acetaminophen and the combination. CONCLUSIONS: Acetaminophen and parecoxib showed no interaction in inhibiting platelet function. In combination they cause a mild degree of COX-1 inhibition corresponding to that of acetaminophen alone.

Red blood cell transfusions in patients undergoing lower extremity artery bypass surgery.

BACKGROUND AND AIMS: The purpose of this study was to search predictors of red blood cell transfusions in peripheral vascular surgical patients. MATERIAL AND METHODS: All the patients who undergone infrainguinal bypass surgery at Helsinki University Hospital in the year 2000 were included. Of 266 records 261 (98%) were available for data review. Multiple stepwise regression model was created to identify independent predictors of blood use. RESULTS AND CONCLUSIONS: 174 (67%) of the patients received red blood cell transfusion. The lowest measured mean (SD) haemoglobin was 94 (11) g/l intraoperatively and 92 (+/- 10) g/l on the first two postoperative days. The median (range) number of units was 3 (1-19). Multivariate analysis showed that high age (p = 0.019), small body surface area (p = 0.017), low preoperative haemoglobin (p < 0.001), blood loss (p < 0.001), long lasting surgery (p<0.001), reoperation (p=0.018), femoro-distal reconstruction (p=0.048) and chronic obstructive pulmonary disease (p = 0.023) increased the risk to receive red blood cell transfusion. The frequent use of antithrombotic medication (72% of the patients) did not significantly increase red blood cell administration. The generous use of red blood cells despite relative safe haemoglobin levels indicates a need for a standardized multidisciplinary transfusion strategy in this patient population. Otherwise, most of the predictors for red blood cell administration were nonmodifiable.

Comparison of ropivacaine 2 mg ml(-1) and prilocaine 5 mg ml(-1) for i.v. regional anaesthesia in outpatient surgery.

BACKGROUND: Ropivacaine 2 mg ml(-1) (0.2%) provides longer-lasting analgesia after deflation of the tourniquet cuff, with fewer side-effects, than lidocaine 5 mg ml(-1) (0.5%) after i.v. regional anaesthesia (IVRA). Whether ropivacaine 2 mg ml(-1) also exerts this advantage over prilocaine 5 mg ml(-1), the local anaesthetic of choice in IVRA in most European countries was investigated in this study. METHODS: Sixty outpatients scheduled for forearm or hand surgery received IVRA with 40 ml of ropivacaine 2 mg ml(-1) (Ropi) or prilocaine 5 mg ml(-1) (Prilo) in a randomized, double-blinded fashion. The development and recovery of pin-prick analgesia and motor power of the hand, as well as ropivacaine and prilocaine plasma concentrations (n=30), were assessed during and after operation. RESULTS: Anaesthesia for surgery was adequate in both groups. Pin-prick analgesia was achieved at a similar rate, except in the radial nerve distribution area where at 10 min 60% of Ropi and 90% of Prilo patients had analgesia (P=0.017). At 10 min 100 and 97% had motor block of the hand in the Ropi and Prilo groups, respectively. Recovery of the sensory block in all innervation areas was already observed 2 min after the tourniquet cuff release. At 10 min after releasing the tourniquet cuff 31% of the Ropi patients and none of the Prilo patients still had analgesia in the median nerve distribution (P=0.004). At 12 min, 42% in the Ropi group and none in the Prilo group had decreased grip strength. After the release of the tourniquet, mean plasma concentrations of ropivacaine were higher than those of prilocaine. The highest individual concentration of ropivacaine was 1.65 microg ml(-1) and that of prilocaine 0.6 microg ml(-1). None of the Ropi patients experienced any symptoms of local anaesthetic toxicity. CONCLUSIONS: Compared with prilocaine 5 mg ml(-1), analgesia in IVRA with ropivacaine 2 mg ml(-1) developed slightly more slowly, while motor block developed at a similar rate. After the release of the tourniquet, sensation recovered quickly and at a similar rate in the two groups, except for a slightly slower recovery after ropivacaine in the innervation area of the median nerve, but no surgically useful extended analgesia after the cuff deflation was observed. Despite a 60% lower milligram-dose, ropivacaine plasma concentrations were markedly higher than those of prilocaine.

Albumin induced hypercoagulability does not reduce blood loss in patients undergoing total hip arthroplasty.

BACKGROUND AND AIMS: Albumin may enhance and hydroxyethyl starch (HES) may impair haemostasis. While the effects are also dependent on haemodilution we minimized it by early structured transfusion therapy, and compared albumin and HES regarding blood loss and coagulation parameters in hip arthroplasty patients. MATERIAL AND METHODS: 101 patients undergoing primary hip arthroplasty received in random order 4% albumin (n = 48) or HES (average Mw 120 kDa/molar substitution ratio 0.7, n = 53). The administration of colloid, red blood cell (RBC), fresh frozen plasma and platetet concentrates begun after a 6-8%, 12-16%, 60% and 100% blood loss of the patient's calculated blood volume respectively. Explanatory risk factors for blood loss were modelled by regression analysis. RESULTS AND CONCLUSIONS: Administration of albumin or HES 1200 ml (500-2000 and 500-1800) [median (range) respectively] did not affect blood loss. The vWF antigen was higher in the albumin group (p = 0.04) postoperatively. Haematocrit value, platelet count, bleeding time, prothrombin time value, activated thromboplastin time, FV activity and fibrinogen concentration were comparable between the groups. Long operation time was associated with great blood loss (p < 0.001). In hip arthroplasty patients with near normal levels of haematocrit albumin enhanced coagulation without altering blood loss.

Characterization of inhibition of platelet function by paracetamol and its interaction with diclofenac in vitro.

BACKGROUND: Paracetamol (acetaminophen) is an effective analgesic and a weak inhibitor of cyclo-oxygenase (COX). Clinically paracetamol is often used together with traditional NSAIDs, which are strong inhibitors of COX. We studied binding of paracetamol to COX and its action on platelet function together with diclofenac. METHODS: Blood was collected from healthy donors and platelet function was assessed by photometric aggregometry, a platelet function analyser (PFA-100, Dade Behring, Deerfield, IL) and by measuring the release of thromboxane B(2) (TxB(2)), the stable metabolite of thromboxane A(2), after addition of paracetamol (10-80 microg ml(-1)). A concentration-inhibition relationship was established and the inhibition coefficient (K(i)) demonstrating 50% binding to COX was determined using a Schild-plot. Interaction of paracetamol (5-20 microg ml(-1)) and diclofenac (0.1-0.8 microg ml(-1)) was determined and an isobolographic analysis was performed. RESULTS: Paracetamol added to platelet-rich plasma (PRP) caused a concentration-dependent inhibition of platelet function. Photometric aggregometry and TxB(2) release was significantly inhibited by paracetamol from 10 microg ml(-1) onwards. The PFA-100 closure time was significantly prolonged by paracetamol at a high concentration only. K(i) was 15.2 microg ml(-1) with a 95% confidence interval of 11.8-18.6 microg ml(-1). Inhibition of aggregation by diclofenac was augmented by paracetamol. Isobolographic analysis showed synergism. CONCLUSIONS: The 95% confidence interval of K(i) equals the antipyretic plasma concentration of paracetamol, i.e. 10-20 microg ml(-1). High doses of paracetamol and a combination of diclofenac and paracetamol cause platelet inhibition and thus may increase risk of surgical bleeding.

Artificial colloids impair haemostasis. An in vitro study using thromboelastometry coagulation analysis.

BACKGROUND: Hydroxyethyl starch (HES) solutions impair haemostatic mechanisms. The impact of the degree of substitution (DS) of a HES solution on thromboelastometry tracings is unclear. Therefore we tested the hypothesis of whether the DS has an effect on the haemostatic defect caused by HES, and assessed whole blood coagulation by thromboelastometry coagulation analysis (ROTEM, Pentapharm Co., Munich, Germany) in serial in vitro haemodilutions of colloids. METHODS: Whole blood was withdrawn from 12 volunteers in a crossover study. Six per cent low-molecular weight HES with a high (HES MW 120 kDa/degree of substitution 0.7) and low (HES MW 130 kDa/0.4) degree of substitution, 4% succinylated gelatin (GEL) or 4% albumin (ALB) was added to citrated venous whole blood samples to make 20, 40, 60 vol.% end-concentrations of each of the solutions. Samples were analyzed by ROTEM. RESULTS: There was a comparable decrease in maximum clot firmness (MCF) and shear elastic modulus [G = 5000 x MCF/(100-MCF)] by HES 120/0.7 and HES 130/0.4 at 20 and 40 vol.% dilutions. At 60 vol.% dilution HES 120/0.7 decreased less alpha-angle and MCF than HES 130/0.4 (P < 0.05). With moderate dilutions all colloids shortened coagulation time (CT). At 20, 40 and 60 vol.% dilutions MCF and G were more decreased in both HES groups than in the ALB and GEL groups (P < 0.05). Furthermore, at 40 and 60 vol.% dilutions G deteriorated more in the GEL than in the ALB group (P < 0.05). CONCLUSION: In vitro the impact of the degree of substitution of HES solution on thromboelastometry coagulation analysis was modest. Haemodilution with gelatin and albumin induced fewer coagulation abnormalities than HES. In addition, the haemodilution with gelatin impaired coagulation more than albumin solution.

Epinephrine added to a lumbar epidural infusion of a small-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the lower extremities.

BACKGROUND: The addition of epinephrine (2 micro g.ml-1) to a thoracic epidural infusion of an opioid-local anesthetic mixture improves analgesia. Here, we studied whether epinephrine could improve analgesia also at lumbar level, when added to an epidural infusion of a low-dose ropivacaine-fentanyl mixture after arterial bypass surgery of the legs. METHODS: Patients in group RFE (n = 21) received a postoperative epidural infusion containing ropivacaine (1 mg.ml-1), fentanyl (2 micro g.ml-1), and epinephrine (2 micro g.ml-1). Patients in group RF (n = 25) received a similar infusion without epinephrine. The infusion speed was 1 ml.10 kg-1. h-1. The infusion was scheduled for 48 h. RESULTS: Epinephrine did not reduce the need for rescue pain medication. Visual analog scale scores (VAS) for pain at rest were low and similar in the groups. Pain intensity was stronger during leg movement [mean VAS 1.5-2.6 (range 0-9)], but it was not affected by the coadministration of epinephrine. The groups did not differ concerning frequency and severity of side-effects. Epinephrine did not reduce fentanyl plasma concentrations. Ropivacaine concentrations were slightly lower in group RFE only in the samples 6 h from the start of the infusion, but not anymore on the first and second postoperative day. CONCLUSION: In the dosage used here, epinephrine did not improve epidural lumbar analgesia. Different distances from the epidural application site to the alpha2-adrenergic receptors of the spinal cord, and differing epinephrine dose requirements may explain why epinephrine as an additive improves epidural analgesia at thoracic, but not at lumbar level.

Propacetamol augments inhibition of platelet function by diclofenac in volunteers.

BACKGROUND: Acetaminophen (paracetamol) enhances the analgesic effect of non-steroidal anti-inflammatory drugs (NSAIDs). Acetaminophen is a weak inhibitor of cyclooxygenase (COX), and its combination with an NSAID may augment COX inhibition-related side effects. METHODS: Ten healthy male volunteers (21-30 yr) were given diclofenac 1.1 mg kg(-1) alone, a combination of propacetamol 30 mg kg(-1) (which is hydrolysed to 50% acetaminophen) and diclofenac 1.1 mg kg(-1) or placebo intravenously in a double blind, crossover study. Platelet function was assessed at 5 min, 90 min and 22-24 h by photometric aggregometry, platelet function analyser (PFA-100(TM)) and by measuring the release of thromboxane B(2) (TxB(2)). Analgesia was assessed with the cold pressor test. RESULTS: Platelet aggregation induced with arachidonic acid was fully inhibited by both diclofenac alone and the combination at the end of the 30-min drug infusion. Propacetamol augmented the inhibition by diclofenac at 90 min (P=0.014). At 22-24 h, platelet function had fully recovered. TxB(2) release was inhibited by the combination of propacetamol and diclofenac at 90 min in comparison with diclofenac alone (P=0.027). PFA-100(TM) detected no difference in platelet function between these two groups. No analgesic effect was detected with the cold pressor test. CONCLUSIONS: The combination of propacetamol and diclofenac inhibits platelet function more than diclofenac alone. This should be considered when assessing the risk of surgical bleeding.

Comparison of hypotensive epidural anaesthesia and spinal anaesthesia on blood loss and coagulation during and after total hip arthroplasty.

BACKGROUND: Hypotensive epidural anaesthesia (HEA) is a technique for reducing peroperative blood loss by significantly lowering mean arterial pressure (MAP). METHODS: Thirty patients scheduled for primary total hip arthroplasty were given HEA (n=15) or spinal anaesthesia (SPA) (n= 15) with bupivacaine in random order. The dose of bupivacaine was titrated to provide epidural blockade up to T1-T4 and spinal blockade at least to T10. Intravenous adrenaline infusion was adjusted to achieve a MAP of about 50-60 mmHg in the HEA group. During SPA MAP was maintained above 70 mmHg with ephedrine, as needed. RESULTS: Intraoperative blood loss (median and 25th and 75th percentiles) was 400 ml (163-575) in the HEA group and 900 ml (663-1,100) in the SPA group (P<0.05). At 3 h postoperatively cumulative blood loss was still smaller in the HEA group (600 ml versus 1,100 ml, P<0.05). The cumulative number of transfused packed red cell concentrate (PRC) units was smaller in the HEA group than in the SPA group during surgery and postoperatively. Prothrombin time value was smaller in the SPA than in the HEA group (69% versus 79%, P<0.05) at 3 h postoperatively. D-dimer concentrations increased more in the SPA group at the end of the surgery and 3 h postoperatively (P<0.05). CONCLUSIONS: HEA resulted in reduced blood loss due to hypotension and reduced number of transfused PRC units during total hip arthroplasty. Based on lower prothrombin time value and higher D-dimer concentrations in the SPA group, the coagulation system might be better preserved during HEA than SPA.

Platelet dysfunction after intravenous ketorolac or propacetamol.

BACKGROUND: Paracetamol is a weak cyclo-oxygenase inhibitor in vitro. A recent study in children has shown that high doses of paracetamol are effective and safe. We studied the effect of propacetamol on haemostasis in adult volunteers. METHODS: Ten volunteers were investigated in a double-blind, randomized, crossover study. They received propacetamol 60 mg kg(-1) or ketorolac 0.4 mg kg(-1) in saline i.v. (30 min) in two different sessions. Platelet function was evaluated before the test infusion (S-0), two (S-2) and 24 h (S-24) after the start of the infusion. Coagulation parameters (PT, APTT, factor V and VII activities) were measured at S-0, S-24 and 48 h (S-48). RESULTS: One of the volunteers had no secondary platelet aggregation in S-0 and was excluded from the final analysis. Two hours (S-2) after propacetamol and ketorolac administration the adrenaline (0.9 microg ml(-1) and 9.0 microg ml(-1)) induced maximal platelet aggregation was decreased compared with S-0. At S-2 platelet aggregation was inhibited more after ketorolac than after propacetamol. At 24 h after ketorolac, but not after propacetamol, there was still a decrease in the adrenaline-induced maximal platelet aggregation. Propacetamol did not affect adenosine diphosphate (ADP)-induced maximal platelet aggregation, whereas ketorolac decreased 3 and 6 microM ADP-induced maximal platelet aggregation at S-2 and S-24. However, 2 h after both ketorolac and propacetamol, thromboxane B2 (TxB2) concentration decreased in platelet rich plasma after 5 min aggregation induced by 8 microM ADP. Coagulation was unaffected. CONCLUSION: Propacetamol 60 mg kg(-1) i.v. causes reversible platelet dysfunction demonstrated by a decrease in maximal platelet aggregation and TxB2 concentration. After 0.4 mg kg(-1) ketorolac i.v. platelet aggregation and TxB2 formation are inhibited more in comparison with propacetamol, and platelet dysfunction is still seen after 24 h.

Hydroxyethyl starch impairs in vitro coagulation.

BACKGROUND: Artificial colloids affect haemostasis. Particularly hydroxyethyl starch (HES) solutions may have detrimental effects on haemostatic mechanisms. METHODS: In a crossover study blood was withdrawn from ten volunteers. Ringer's acetate, 6% low molecular weight HES (MW 120,000/molar substitution ratio 0.7), 10% low molecular weight HES MW 200,000/0.5) and 6% high molecular weight HES (MW 400,000/0.7) or 4% albumin was added to venous blood samples to make either 20 vol.% or 50 vol.% concentrations of each of the solutions. Samples were analyzed by thrombelastography (TEG). RESULTS: All HES solutions at 20 vol.% concentration impaired haemostasis as demonstrated by decreased clot formation rate (alpha-angle and maximum amplitude (MA)). In contrast, Ringer's acetate and albumin improved coagulability at 20 vol.% concentrations. Coagulation time (r + K) was prolonged at 50 vol.% dilutions of all solutions. The median r + K was greater with HES 400 (P < 0.05) and HES 200 (N.S.) than with HES 120. CONCLUSION: We conclude that HES at 20 and 50 vol.% concentrations has an adverse effect on in vitro measures of coagulation. A 50% dilution with high molecular weight HES seems to impair coagulation more than low molecular weight HES. Ringer's acetate and albumin caused a hypercoagulable state at a concentration of 20 vol.%, but the higher concentration decreased coagulability.

Comparison of the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit prostaglandin synthesis which may result in impaired platelet function. Because NSAIDs have different abilities to inhibit cyclo-oxygenases we compared the effect of intravenous ketoprofen, ketorolac and diclofenac on platelet function in volunteers. METHODS: Ten healthy male volunteers were given ketoprofen 1.4 mg x kg(-1), ketorolac 0.4 mg x kg(-1) and diclofenac 1.1 mg x kg(-1) in saline i.v. on three different occasions, at more than one-week intervals, in a randomized double-blind crossover study. Platelet function was evaluated before (sample 0), 2 (sample 2) and 24 h (sample 3) after the beginning of the infusion. RESULTS: Two of the volunteers had no secondary platelet aggregation in their aggregation curves before the experiment (sample 0, studied three times) and their results were excluded from the final analysis. Diclofenac inhibited adrenaline (0.9 microg x m[-1]) induced platelet aggregation less (median maximal aggregation 22.5%) than ketoprofen (18.3%) and ketorolac (15.7%) (P<0.05) in sample 2. In the ketorolac group in sample 3 an impairment of adrenaline (0.9 microg x ml[-1]) induced platelet aggregation was still seen (26.7%) (P<0.05) but not in the other groups. Diclofenac did not affect adenosine diphosphate (ADP) induced platelet aggregation. However, ketorolac caused an impairment in ADP (3 microM and 6 microM) induced platelet aggregation and ketoprofen in ADP (6 microM) induced platelet aggregation in sample 2. Bleeding time was prolonged (P<0.05) after ketoprofen and ketorolac (sample 2) but not after diclofenac. Platelet retention on glass beads was unaffected by the tested drugs. CONCLUSION: Ketoprofen, ketorolac and diclofenac caused a reversible platelet dysfunction. Diclofenac had the mildest effect, while platelet dysfunction was still seen 24 h after the beginning of ketorolac.

Haemostatic changes caused by i.v. regional anaesthesia with lignocaine.

The various components of i.v. regional anaesthesia (IVRA), that is ischaemia, tourniquet compression and the presence of high concentrations of local anaesthetics in the blood vessels of the extremity, may affect haemostatic mechanisms. We performed a cross-over study in 10 healthy male volunteers to examine the role of lignocaine in IVRA on several haemostatic variables, and those indicating fibrinolysis and platelet function in particular. Venous blood samples were obtained from the test arm and the opposite arm before IVRA, at the time of tourniquet cuff deflation and 30 min thereafter. Metal needle punctures were used, and for the sample from the test arm at the time of cuff deflation, cuff pressure was reduced from 300 mm Hg to individual mean arterial pressure. The IVRA technique included exsanguination by arm elevation and axillary artery compression, inflation of the tourniquet cuff for 20 min and deflation of the cuff in one step (after obtaining the venous sample). Each subject received, in random order, either 0.5% lignocaine 3 mg kg-1 or the corresponding volume of saline i.v. All fibrinolysis markers, that is, D-dimer, tissue plasminogen activator antigen (t-PA antigen), tissue plasminogen activator activity (t-PA activity), plasminogen activator inhibitor activity (PAI) and protein C indicated enhanced fibrinolysis by IVRA, but only t-PA antigen and PAI showed greater changes in the lignocaine compared with the saline group in the exposed arm at the time of cuff deflation. Platelet function tests (ADP-induced platelet aggregation, beta-thromboglobulin and thrombelastogram (TEG)) indicated no differences between the lignocaine and saline groups. Although IVRA appeared to induce some platelet dysfunction, there was a small increase in TEG amplitude indicative of improved fibrin-platelet interaction in the lignocaine-exposed arm at the time of cuff deflation. We conclude that the presence of high i.v. lignocaine concentrations (median 144.4 micrograms ml-1 in cubital veins at the end of the tourniquet time) potentiated ischaemia-induced fibrinolysis activation during IVRA. Concomitant platelet dysfunction was not aggravated by lignocaine.