Effects of celecoxib on blood loss, pain, and recovery of function after total knee replacement: a randomized placebo-controlled trial.

BACKGROUND: Pain management after surgery has been used as a sales argument for the use of COX-2 inhibitors, but their potential positive and negative effects have not been fully investigated. We thus conducted a controlled evaluation of the effect of celecoxib on perioperative blood loss, pain relief and consumption of analgesics, range of motion, and subjective outcome in conjunction with total knee replacement (TKR). METHOD: 50 patients were randomized to either placebo or celecoxib (200 mg) preoperatively and then twice daily. Total blood loss was calculated by the Hb balance method, taking the patient's pre- and postoperative hemoglobin and blood volume into account. Pain scores (VAS), range of motion, and subjective outcome (KOOS) were monitored postoperatively and during the first year after surgery. RESULTS: No differences in total, hidden, or drainage blood loss were found between the groups. There were 30% lower pain scores during the first 4 weeks after surgery and lower morphine consumption after surgery in the celecoxib group, while no effect was seen on pain, range of motion, and subjective outcome at the 1 year follow-up. INTERPRETATION: Celecoxib does not increase perioperative blood loss but reduces pain during the postoperative period after TKR. It is not necessary to discontinue celecoxib before surgery. The postoperative use of celecoxib did not increase range of motion or subjective outcome 1 year after TKR.

Enhanced rate of ethanol elimination from blood after intravenous administration of amino acids compared with equicaloric glucose.

AIMS: To investigate the effect of an amino acid mixture given intravenously (i.v.) on the rate of ethanol elimination from blood compared with equicaloric glucose and Ringer's acetate as control treatments. METHODS: In a randomized cross-over study, six healthy men (mean age 23 years) fasted overnight before receiving either Ringer's acetate, glucose or the amino acid mixture (Vamin 18 g N/l) by constant rate i.v. infusion over 4.5 h. Ethanol (0.4 g/kg) was given by an i.v. infusion lasting 60 min during the time each of the treatments was administered. At various times post-infusion, blood samples were taken for determination of ethanol by headspace gas chromatography. Blood glucose and heart rate were monitored at regular intervals. Concentration-time profiles of ethanol were plotted for each subject and the rate of ethanol disappearance from blood as well as other pharmacokinetic parameters were compared by repeated measures analysis of variance. RESULTS: The rate of ethanol elimination from blood was increased significantly (P < 0.001) after treatment with amino acids (mean +/- SD, 0.174 +/- 0.011 g/l/h) compared with equicaloric glucose (0.121 +/- 0.016 g/l/h) or Ringer's acetate (0.110 +/- 0.013 g/l/h). Heart rate was also slightly higher during infusion of the amino acid mixture (P < 0.05). CONCLUSIONS: When the rate of ethanol elimination from blood is relatively slow, such as after an overnight fast, it can be increased by approximately 60% after treatment with i.v. amino acids. The efficacy of amino acid treatment was not related to the supply of calories because glucose was no more effective than Ringer's acetate. We suggest that amino acids might increase hepatic oxygen consumption, resulting in a more effective conversion of NADH to NAD+ in mitochondria. An important feature of the experimental design was ensuring hepatic availability of amino acids during much of the time that ethanol was being metabolized.

Blood loss after total hip replacement: a prospective randomized study between wound compression and drainage.

A randomized, controlled study compared the effects of wound compression with drainage after primary total hip arthroplasty. In 51 patients, an inflatable cuff was placed over the wound underneath a girdle (System Calmed, Calmed AB, Askim, Sweden). Control patients had wound drainage (n = 54). Preoperative and intraoperative variables did not differ between groups. Total blood loss was calculated using hemoglobin balance; with compression it was 1510 +/- 656 mL (mean +/- SD) and in controls 1695 +/- 712 mL (P = .13). However, less blood was transfused in the compression group (P = .05). Wound infection was seen in 2 patients with compression and in 3 controls. Deep venous thrombosis occurred in 3 controls. Wound discharge was more frequent in controls (19/54 vs 8/51; P = .04). Thus, wound compression had no obvious negative effects and reduced wound discharge and need for transfusion. It may replace drainage after total hip arthroplasty.

Measuring the size of the extracellular fluid space using bromide, iohexol, and sodium dilution.

There is a need to find methods to assess the size of the extracellular fluid (ECF) volume without involving radioactive tracers. For this purpose, we applied 3 methods for measuring the ECF volume in 10 male volunteers (mean age, 34 yr). Steady-state plasma bromide concentration (control) was compared to the results of kinetic analysis of plasma iohexol and to kinetic analysis of the dilution of serum sodium after IV infusion of 1 L of isotonic mannitol. The volume of distribution of these tracers was used to indicate the ECF volume. The results disclosed statistically significant correlations between the results of all 3 methods, although the average sodium dilution showed 0.7 L lower values than iohexol and 1.4 L lower than bromide. All three methods correlated significantly with body weight. The percentage of the body weight indicated by the methods was 18.3% (3.1%) for sodium, 19.6% (1.0%) for iohexol, and 20.5% (1.1%) for bromide. We conclude that sodium dilution may be performed at bedside but iohexol and bromide showed less intersubject variability. Iohexol simultaneously measures the glomerular filtration rate and should be a viable clinical option if the hospital performs routine assessments of kidney function using this tracer.

Tranexamic acid in total hip arthroplasty saves blood and money: a randomized, double-blind study in 100 patients.

BACKGROUND: A blood transfusion is a costly transplantation of tissue that may endanger the health for the recipient. Blood transfusions are common after total hip arthroplasty. The total saving potential is substantial if the blood loss could be reduced. Studies on the use of tranexamic acid have shown interesting results, but its benefits in total hip arthroplasty have not yet been resolved. PATIENTS AND METHODS: 100 patients receiving a total hip arthroplasty (THA) got a single injection of tranexamic acid (15 mg/kg) or placebo intravenously before the start of the operation. The study was double-blind and randomized. Total blood loss was calculated from the hemoglobin (Hb) balance. Volume and Hb concentration of the drainage was measured 24 h after the operation. Intraoperative blood loss was estimated volumetrically and visually. RESULTS: The patients who received tranexamic acid (TA) bled less. The total blood loss was on average 0.97 L in the TA group and 1.3 L in the placebo group (p < 0.001). 8/47 (0.2) in the TA group were given blood transfusion versus 23/53 (0.4) in the placebo group (p = 0.009). Drainage volume and drainage Hb concentration were less in the TA group (p < 0.001 and p = 0.001). No thromboembolic complications occurred. INTERPRETATION: Considering the cost of blood and tranexamic acid only, use of the drug would save EUR 47 Euro per patient. We recommend a preoperative single dose of tranexamic acid for standard use in THA.

Nitric oxide does not cause extravasation in endotoxemic rats.

BACKGROUND: Nitric oxide (NO) formed from inducible NO synthase (iNOS) is assumed to promote vascular permeability in sepsis and endotoxemia. METHODS: Thirty-seven anesthetized rats were examined for the effects of endotoxin. After randomization, 17 animals had lipopolysaccharide (LPS) administered and 20 rats served as controls and were given the corresponding volume of saline. The observation period was 5 hours after administration of endotoxin. Mean arterial blood pressure, heart rate, and hematocrit were recorded in all animals, and transcapillary exchange of albumin, tissue water content, immunohistochemistry for nitric oxide synthase, and blood gases were investigated in subsets of animals. RESULTS: When anesthetized rats were studied for 5 hours after endotoxin (LPS), the sequestration of albumin decreased in the intestine (double-isotope method) and there was no increased water content (freeze-drying technique) when the elevated tissue plasma volume of the LPS-treated rats was corrected for. Immunohistochemical methods showed a similar distribution and intensity of staining for endothelial NOS and neuronal NOS in LPS and control groups. In the lung of the LPS-treated rats, there was a significantly larger number of infiltrating, inflammatory cells staining for iNOS. There was no iNOS demonstrated in vascular structures or heart. CONCLUSION: At 5 hours after LPS, there was no increased loss of water or albumin from the circulation. This challenges the notion that NO causes vascular damage in endotoxemia and extravasation as an obligatory sequela to endotoxemia.