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.

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.

Propacetamol and diclofenac alone and in combination for analgesia after elective tonsillectomy.

BACKGROUND: Diclofenac and paracetamol have different mechanisms and sites of action. Therefore, we tested if their combination is more effective for analgesia after tonsillectomy than either drug alone with respect to rescue analgesic consumption and visual analog scale values. METHODS: The analgesic effects of intravenously administered propacetamol (injectable pro-drug of paracetamol) and diclofenac or a combination on postoperative pain were compared in 71 adult elective tonsillectomy patients in a randomized, double-blind study. After induction of anesthesia the patients received monotherapy with 2 g propacetamol (n = 25) or 75 mg diclofenac (n = 25), or a combined treatment with 2 g propacetamol and 75 mg diclofenac (n = 21) in physiologic saline as an infusion. Postoperatively the propacetamol dosage was repeated twice and diclofenac once on the ward. Oxycodone (0.03 mg kg(-1)) was used as a rescue analgesic by patient-controlled analgesia. RESULTS: On average the patients needed oxycodone 15.3, 13.2 and 10.6 times in the propacetamol, diclofenac and combination groups, respectively (NS). A verbal rating scale and a visual analog scale were employed for assessing post-tonsillectomy pain, nausea and patient satisfaction in all groups. No statistically significant differences were found between the groups. Twelve of the 25 (48%) patients having received propacetamol complained of pain at the cannulation site. CONCLUSION: Combined treatment with propacetamol and diclofenac with the dosages used provided clinically only a minor advantage over monotherapy with propacetamol or diclofenac with respect to postoperative analgesia or the incidence of side-effects in adult tonsillectomy patients.

Comparison of the opioid-sparing efficacy of diclofenac and ketoprofen for 3 days after knee arthroplasty.

BACKGROUND: Comparative postoperative non-steroidal anti-inflammatory drug (NSAID) studies in orthopedic patients have usually been restricted in time to the first postoperative day. The opioid-sparing effect of NSAIDs may be beneficial postoperatively as long as pain otherwise restricts ambulation and rehabilitation. We therefore compared the analgesic efficacy of the maximum recommended doses of diclofenac and ketoprofen for 3 days after knee arthroplasty. METHODS: We studied 64 knee arthroplasty patients, operated on under spinal anesthesia. In a randomized, double-blind and placebo-controlled fashion, the patients received either i.v. diclofenac 75 mg (n = 24), ketoprofen 100 mg (n = 24) or saline (n = 16) in the recovery room, followed by oral diclofenac 150 mg/day, ketoprofen 300 mg/day or placebo, respectively, for 3 days, supplemented by patient-controlled analgesia (PCA) with i.v. oxycodone. RESULTS: The mean consumption of oxycodone during the first, second and third study days was 45.3, 22.3 and 15.2 mg in the diclofenac group, 43.5, 37.5 and 21.8 mg in the ketoprofen group, and 61.2, 45.9 and 36.1 mg, respectively, in the placebo group. Oxycodone consumption was significantly lower (P < 0.05) in the ketoprofen group than in the placebo group in the postoperative period 13-24 h and 61-72 h. Diclofenac was superior to placebo in the postoperative period 25-48 h (P < 0.01), 49-60 h (P < 0.05) and to ketoprofen at 49-60 h (P < 0.05). During administration of diclofenac on days 1-3 and ketoprofen on day 2, the mean pain scores (VAS) were lower than in the placebo group (P < 0.05). Six patients had difficulties in operating the PCA device. There were no differences in blood loss. CONCLUSION: We conclude that in the first day after knee arthroplasty (13-24 h), ketoprofen exerted an opioid-sparing effect. After day 1 (25-60 h), with the doses used, diclofenac proved to be better than placebo, whereas ketoprofen was not.

Erythrocyte counts in the cerebrospinal fluid associated with continuous spinal anaesthesia.

Continuous spinal anaesthesia technique can be associated with peridural haemorrhage due to blood vessel damage caused by the needle or the catheter. We studied whether thrombosis prophylaxis or anticoagulation medications increase the risk of subarachnoid haemorrhage when continuous spinal anaesthesia is used. Twenty arthroplasty patients received low-molecular-weight heparin preoperatively and twenty-two vascular surgery patients received heparin (100 IU kg-1) peroperatively; eight of the latter patients were on regular preoperative antiplatelet medication. Twenty-four prostate surgery patients, not exposed to heparin or other drugs affecting coagulation, served as controls. A 22-gauge spinal catheter was used and bupivacaine was injected through the catheter. Within the following 24 hours, 4-5 cerebrospinal fluid samples were collected for erythrocyte counts. In the arthroplasty and the vascular group there were five patients each and in the control group seven patients with more than 100 x 10(6) l-1 erythrocytes in at least one of the samples. The highest erythrocyte count was 23900 x 10(6) l-1 in a control patient. The 24-hour sample was blood-tinged (erythrocytes > 1000 x 10(6) l-1) in two patients in the arthroplasty group, in one patient in the vascular group and in four patients in the control group. In spite of the haemorrhages detected in this study, no related neurological symptoms or other serious consequences were observed. The risk of subarachnoid haemorrhage was not increased by drugs affecting coagulation.

Haemodynamic changes during spinal anaesthesia with slow continuous infusion or single dose of plain bupivacaine.

Forty elderly patients, scheduled for orthopaedic surgery of the hip or knee were studied. Twenty patients received a single-dose spinal anaesthesia with 3 ml of plain 0.5% bupivacaine (SDSA group). Twenty patients received continuous spinal anaesthesia using a 32- or 22-gauge catheter. A bolus of 1.0 ml of plain 0.5% bupivacaine was given to ten patients and 0.5 ml to another ten, continued by an infusion at a rate of 2 ml/h. The spread of analgesia and haemodynamic changes (central venous pressure, arterial pressures, need for sympathomimetic medication) were registered. The mean dose of bupivacaine was 2.9 ml (range 1.5-5 ml) in the CSA group (3.0 ml in the SDSA group). Eight patients in the CSA group needed medication for pain during surgery compared to five patients in the SDSA group (n.s.). The median level of pinprick analgesia at 60 min was T11 in the CSA and T6.5 in the SDSA group (P less than 0.01). The mean maximum decreases in CVP and MAP were quite similar in the CSA and SDSA group (2.1 vs 2.8 mmHg (0.3 vs 0.4 kPa) and 17 vs 21 mmHg (2.3 vs 2.8 kPa), respectively) (n.s.). Six patients in the SDSA group and four patients in the CSA group needed sympathomimetic medication. It is concluded that titration of bupivacaine for spinal anaesthesia caused only minor haemodynamic changes which were similar to those after single-dose spinal bupivacaine.

Technical problems associated with the use of 32-gauge and 22-gauge spinal catheters.

Interest in the use of continuous spinal anaesthesia (CSA) has recently increased because of the availability of new, extremely thin catheters. In this study the use of 32-gauge (G) catheters was compared with 22-G catheters in operations on the lower limb and for the administration of intrathecal morphine in the postoperative period in 42 elderly patients. CSA succeeded in 34 cases and 8 patients were anaesthetised with a single-shot spinal method. No general anaesthesia was needed. Technical problems with the subarachnoid puncture with the 19-G needle caused two failures in the 22-G group. In a group of 20 patients, there were five failures with the 32-G catheter, as opposed to one failure with the 22-G catheter in a group of 20 patients. Associated with morphine injection through the 32-G catheter, the syringe or connector was inadvertently disconnected in four cases and a tear of the catheter wall was observed in one case. Such problems did not occur with the 22-G catheter. Postdural puncture headache did not occur, and there was no difference in the incidence of patient-reported postoperative complications between the two groups. It is concluded that both the insertion and maintenance of the thin (32-G) subarachnoid catheters are associated with more technical problems than the 22-G catheter.