Basal and cold-induced fatty acid uptake of human brown adipose tissue is impaired in obesity.

Fatty acids (FA) are important substrates for brown adipose tissue (BAT) metabolism, however, it remains unclear whether there exists a difference in FA metabolism of BAT between lean and obese healthy humans. In this study we evaluated supraclavicular BAT fatty acid uptake (FAU) along with blood perfusion in lean and obese subjects during cold exposure and at room temperature using positron emission tomography (PET)/computed tomography (CT). Additionally, tissue samples were taken from supraclavicular region (typical BAT region) from a subset of subjects to evaluate histological presence of BAT. Non-shivering cold stress elevated FAU and perfusion of BAT in lean, but not in obese subjects. Lean subjects had greater FAU in BAT compared to obese subjects during cold exposure and interestingly also at room temperature. The higher BAT FAU was related to younger age and several indicators of superior systemic metabolic health. The subjects who manifested BAT histologically had several folds higher BAT FAU compared to subjects with no such histological manifestation. Together, obese subjects have less active tissue in supraclavicular region both in basal and cold-activated state and the FA metabolism of BAT is blunted in obesity.

Enhancement of bulk second-harmonic generation from silicon nitride films by material composition.

We present a comprehensive tensorial characterization of second-harmonic generation from silicon nitride films with varying compositions. The samples were fabricated using plasma-enhanced chemical vapor deposition, and the material composition was varied by the reactive gas mixture in the process. We found a six-fold enhancement between the lowest and highest second-order susceptibility, with the highest value of approximately 5 pm/V from the most silicon-rich sample. Moreover, the optical losses were found to be sufficiently small (below 6 dB/cm) for applications. The tensorial results show that all samples retain in-plane isotropy independent of the silicon content, highlighting the controllability of the fabrication process.

Brown adipose tissue triglyceride content is associated with decreased insulin sensitivity, independently of age and obesity.

The aim of the present study was to determine whether single-voxel proton magnetic resonance spectroscopy ((1)H-MRS) can non-invasively assess triglyceride content in both supraclavicular fat depots and subcutaneous white adipose tissue (WAT) to determine whether these measurements correlate to metabolic variables. A total of 25 healthy volunteers were studied using (18)F-fluorodeoxyglucose positron emission tomography (PET) and (15)O-H2O PET perfusion during cold exposure, and (1)H-MRS at ambient temperature. Image-guided biopsies were collected from nine volunteers. The supraclavicular triglyceride content determined by (1)H-MRS varied between 60 and 91% [mean ± standard deviation (s.d.) 77 ± 10%]. It correlated positively with body mass index, waist circumference, subcutaneous and visceral fat masses and 8-year diabetes risk based on the Framingham risk score and inversely with HDL cholesterol and insulin sensitivity (M-value; euglycaemic-hyperinsulinaemic clamp). Subcutaneous WAT had a significantly higher triglyceride content, 76-95% (mean ± s.d. 87 ± 5%; p = 0.0002). In conclusion, the triglyceride content in supraclavicular fat deposits measured by (1)H-MRS may be an independent marker of whole-body insulin sensitivity, independent of brown adipose tissue metabolic activation.

The use of balanced HES 130/0.42 during complex cardiac surgery; effect on blood coagulation and fluid balance: a randomized controlled trial.

INTRODUCTION: Colloids and crystalloid are used during cardiac surgery for priming of the cardiopulmonary bypass (CPB) circuit. Colloids may decrease postoperative fluid balance because of their high oncotic pressure and low risk of fluid extravasation. On the other hand, colloids have been shown to impair blood coagulation. MATERIALS AND METHODS: In a prospective, randomized, double-blinded study, 50 patients scheduled for coronary artery bypass grafting or a valve procedure were planned to be randomized to receive either balanced 6% HES130/0.42 or Ringer-acetate solution for CPB priming. Randomization was stopped prematurely after 35 randomized patients (19 in the HES and 16 in the Ringer groups) because of the published report where HES130/0.42 was associated with impaired renal function. Effects on haemostasis and fluid balance were investigated. RESULTS: The rotational thromboelastometry (ROTEM®) parameters and chest tube drainage on the first postoperative morning (1POM) were comparable between the groups (p>0.05). However, patients in the HES group needed more blood and blood product transfusions. The total volume administered into the CPB circuit was lower in the HES than in the Ringer (RIN) group, 2905±1049 mL versus 3973±1207 mL (p=0.011), but there was no statistically significant difference in total fluid balance on the 1POM (5086±1660 mL in the HES group versus 5850±1514 mL in the RIN group, respectively). CONCLUSIONS: After complex cardiac surgery, the use of balanced 6% HES130/0.42 solution for CPB circuit priming did not impair haemostasis measured by ROTEM®, but it increased the need for transfusions. Fluid balance after CPB was less positive in the HES group, but, on the 1POM, it was comparable between the groups.

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.

Hydroxyethylstarch and gelatin solutions impair blood coagulation after cardiac surgery: a prospective randomized trial.

BACKGROUND: Colloids are often used after cardiac surgery as intravascular volume replacement therapy. Cardiac surgical patients have an increased risk of bleeding. Both hydroxyethylstarch (HES) and gelatin solutions impair haemostasis. We examined the impact and dose effect on coagulation of HES 130/0.4, gelatin, or Ringer's acetate solutions after cardiac surgery. METHODS: Forty-five patients received three boluses (each 7 ml kg(-1)) of either 6% HES 130/0.4, 4% gelatin, or Ringer's acetate solution after elective cardiac surgery. The infusion of study solution was continued in the dose 7 ml kg(-1) over the following 12 h. The total dose of study solution was 28 ml kg(-1). Hypovolaemia was treated with Ringer's acetate. Modified thromboelastometry was performed to detect coagulation disorders. RESULTS: Clot formation time was prolonged and clot strength decreased after infusion of 7, 14, and 21 ml kg(-1) of either colloid compared with the Ringer's acetate group. After infusion of 14 and 21 ml kg(-1) of Ringer's acetate, clot strength was slightly, but significantly, increased. On the first postoperative morning, clot strength was still decreased in the gelatin group in comparison with the Ringer's acetate group. Neither HES nor gelatin induced fibrinolysis. Chest tube drainage was comparable between all groups. CONCLUSIONS: Even a small dose of HES 130/0.4 or gelatin impaired clot strength after cardiac surgery in a dose-dependent fashion, but neither colloid increased blood loss.

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.

Haemodynamics and acid-base equilibrium after cardiac surgery: comparison of rapidly degradable hydroxyethyl starch solutions and albumin.

BACKGROUND: Stable haemodynamics is often achieved by administration of colloids after cardiac surgery. We conducted a prospective, randomized, open-label study comparing haemodynamics and acid-base equilibrium after infusion of two rapidly degradable hydroxyethyl starch (HES) solutions or human albumin (HA) to cardiac surgical patients. MATERIALS AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 6% HES (mW 130 kDa, n = 15), 6% HES (MW 200 kDa, n = 15) or 4% HA (MW 69 kDa, n = 15) after on-pump cardiac surgery. RESULTS: Left ventricular filling pressures assessed using pulmonary artery catheter responded similarly in all groups. mean (SD) cardiac index was higher in HES130 [3.5 l min(-1) m(-2) (0.7) ] and HES200 [3.5 l min(-1) m(-2) (0.5)] than in HA [2.8 l min(-1) m(-2) (0.6)] group after completion of infusion (P = 0.002) but no differences were detected at 2 and 18 hours. Oxygen delivery increased in both HES groups but not in HA group. After cessation of infusion base excess was the most negative in Ha group. At 2 hours mean (SD) base excess was higher in HES130 [0 (1.32)] than in HES200 [-1.32 (2.27) ] and HA [-2.3 (1.3)] group (P = 0.002, between the groups). CONCLUSIONS: We conclude that the effect of albumin on cardiac performance is inferior than that of HES130 or HES200 in early postoperative phase after cardiac surgery. HES130 induces no alterations in acid-base equilibrium whereas a negative base excess was observed after HA infusion.

Interplay between coagulation and inflammation in open and endovascular abdominal aortic aneurysm repair--impact of intra-aneurysmal thrombus.

AIMS: Our aim was to compare hemostatic and inflammatory mechanisms in abdominal aortic aneurysm (AAA) patients after open surgery (OPEN) and endovascular AAA repair (ENDO). SUBJECTS AND METHODS: From the 32 consecutive AAA patients recruited, 17 represented ENDO and 15 OPEN. The intra-aneurysmal thrombus was removed during OPEN, but stayed intact after ENDO. The preoperative volume of the intra-aneurysmal thrombus was calculated from computed tomography images. Markers of coagulation and inflammation were studied preoperatively, at one, two, three, four and seven days and at three months postoperatively. RESULTS: Preoperative upregulation of F 1+2, TAT and D-dimer was evident in both groups. The volume of intra-aneurysmal thrombus correlated with CRP (beta = 0.62, p = 0.001), IL-6 (beta = 0.60, p = 0.001) and PAI-1 ag (beta = 0.51, p = 0.007). Surgery further enhanced inflammation, coagulation and fibrinolysis. IL-6 increased in both groups, but the increases of CRP and PIIINP were higher in the OPEN group. Postoperative CRP correlated with the intra-aneurysmal thrombus volume in the ENDO group. At three months D-dimer (p < 0.05) was higher than preoperatively in the ENDO, in contrast to the OPEN group. CONCLUSION: Preoperatively both prothrombotic and fibrinolytic mechanisms are activated in patients with AAA. Intraluminal thrombus induces prothrombotic and inflammatory interactions, which persist after endovascular aortic aneurysm repair.

Effect of 3 g of intravenous paracetamol on post-operative analgesia, platelet function and liver enzymes in patients undergoing tonsillectomy under local anaesthesia.

BACKGROUND: Paracetamol is often given as an adjunctive analgesic to reduce opioid-related adverse effects but its optimal dose is unknown. We studied the analgesic effect and safety of a single 3-g intravenous (i.v.) dose of paracetamol in adults. METHODS: One hundred and seven patients undergoing tonsillectomy under local anaesthesia were randomly allocated to receive i.v. 3 g of paracetamol, 75 mg of diclofenac or placebo prior to surgery. The consumption of post-operative morphine using a patient-controlled analgesia-device was quantified for 6 h. Platelet aggregation and the concentrations of paracetamol, liver aminotransferases, glutathione transferase alpha 1-1 (GSTA1-1) and thromboxane B(2) were measured. RESULTS: During the first hours after surgery, both paracetamol and diclofenac reduced (P < 0.05) the consumption of morphine but had no effect thereafter. The values for the 6-h cumulative consumption of morphine in patients given paracetamol (18.7 +/- 13.8 mg), diclofenac (16.1 +/- 9.9 mg) and placebo (22.0 +/- 12.1 mg) did not differ. Paracetamol had no effect on platelet aggregation, which was impaired only by diclofenac in response to arachidonic acid (P < 0.005). Both paracetamol (P < 0.01) and diclofenac (P < 0.005) inhibited the release of thromboxane B(2) at 1 h but they did not affect serum aminotransferase and GSTA1-1 levels. One patient given paracetamol displayed a transient increase in GSTA1-1 and liver aminotransferases. CONCLUSION: During the initial hours after tonsillectomy, the administration of 3 g of i.v. paracetamol and 75 mg of diclofenac reduced the consumption of morphine. Both drugs also reduced the release of thromboxane B(2) from activated platelets but only diclofenac had a negative effect on platelet aggregation. In sensitive individuals, large doses of paracetamol may disturb the hepatocellular integrity. We do not recommend the use of i.v. doses of paracetamol higher than 1 g.

A comparison of the haemodynamic effects of 4% succinylated gelatin, 6% hydroxyethyl starch (200/0.5) and 4% human albumin after cardiac surgery.

BACKGROUND AND AIMS: The goal for volume replacement therapy is to maintain stable haemodynamics after cardiac surgery. We hypothesized that a short term infusion of hydroxyethyl starch results in better haemodynamic response than an infusion of lower molecular weight gelatin. MATERIAL AND METHODS: 45 patients received a predetermined fixed dose of 15 ml kg(-1) of either 4% succinylated gelatin (GEL) or 6% hydroxyethyl starch (HES) or 4% human albumin (HA) after cardiac surgery. RESULTS AND CONCLUSIONS: Pulmonary capillary wedge pressure was more increased in GEL and HES groups [mean (SD) 153% (54) and 168% (57) of pre-infusion value] than in HA group [122% (23)] (P = 0.031) after completion of infusion, but no differences in cardiac index (CI) and stroke volume index (SVI) were observed. At 2 and 18 hours after end of study infusions SVI was more increased in HES [143% (38) and 148% (41) of pre-infusion values] and HA [143% (35) and 163% (42) of pre-infusion values] groups than in GEL [116% (23) and 125% (30)] group (P = 0.047 at 2 hours and P = 0.033 at 18 hours). In early postoperative phase after cardiac surgery, HES and HA infusions improve haemodynamics more and longer period than GEL infusion.

Acute renal injury and dysfunction following elective abdominal aortic surgery.

OBJECTIVES: To evaluate the incidence of kidney injury and acute renal dysfunction (ARD) and associated risk factors in open abdominal aortic surgery. MATERIALS AND METHODS: 69 patients undergoing elective infrarenal aortic repair were included in a prospective study. Anaesthesia and haemodynamic management were standardised targeting a mean arterial pressure (MAP) of 70-90 mmHg, pulmonary artery occlusion pressure of 12-14 mmHg and cardiac index >or=2.4 l/min/m(2). Urinary albumin-creatinine and N-acetyl-B-D-glucosaminidase-creatinine ratios were measured as indicators of kidney injury. The definition of ARD was based on the RIFLE criteria. RESULTS: Kidney injury was found in most patients. ARD developed in 22% of the patients, and acute renal failure in 4%. The patients with ARD were older, and had lower plasma creatinine and estimated GFR before surgery. ARD was associated with intraoperative hypotension (MAP <60 mmHg >15 min), low cardiac index (<2.4 l/min/m(2)), rhabdomyolysis, and early reoperation. Intraoperative hypotension and postoperative low cardiac output were independent risk factors for ARD in multivariate analysis. CONCLUSIONS: Kidney injury occurs in most patients undergoing infrarenal aortic surgery, but only 22% develop acute renal dysfunction. Hypotension and low cardiac output are risk factors that could be avoided by optimizing perioperative management.

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.