Search

Background This is a secondary publication of a PhD thesis. Local infiltration analgesia (LIA) is a new multimodal wound infiltration method for treating postoperative pain after knee and hip arthroplasty. This method is based on systematic infiltration of a mixture of ropivacaine, a long acting local anaesthetic, ketorolac, a cyclooxygenase inhibitor (NSAID), and adrenalin around all structures subject to surgical trauma in knee and hip arthroplasty. Aims Paper I: to assess whether pain relief after LIA in total knee arthroplasty (TKA) is as effective as femoral block. Paper II: to assess whether the plasma concentration of ropivacaine and ketorolac after LIA in TKA reaches levels linked to toxicity. Paper III: to assess whether the plasma concentration of unbound ropivacaine after LIA in THA reaches levels linked to toxicity and if it is higher in THA as compared to TKA. Paper IV: to assess whether the plasma concentration of ketorolac after LIA in THA reaches levels linked to toxicity, and whether administration of ketorolac in LIA is safer as compared to the intramuscular route. Methods Two patient cohorts of 40 patients scheduled for elective total knee arthroplasty (TKA) and 15 patients scheduled for total hip arthroplasty (THA) contributed to this work. In a randomized trial the efficacy of LIA in TKA with regard to pain at rest and upon movement was compared to femoral block. Results Both methods result in a high quality pain relief and similar morphine consumption during the 24 h monitoring period. In the same patient cohort the maximal total plasma concentration of ropivacaine was below the established toxic threshold for most patients. All patients in the THA cohort were subjected to the routine LIA protocol. In these patients both the total and unbound plasma concentration of ropivacaine was determined. The concentration was below the established toxic threshold. As ropivacaine binds to α–1 acid glycoprotein (AAG) we assessed the possibility that increased AAG may decrease the unbound concentration of ropivacaine. A 40% increase in AAG was detected during the first 24 h after surgery, however the fraction of unbound ropivacaine remained the same. There was a trend towards increased C max of ropivacaine with increasing age and decreasing creatinine clearance but the statistical power was too low to draw any conclusion. Administration of 30 mg ketorolac according to the LIA protocol both in TKA and THA resulted in a similar C max as previously reported after 10 mg intramuscular ketorolac. Neither age, nor body weight or BMI, nor creatinine clearance, correlates to maximal ketorolac plasma concentration or total exposure to ketorolac (AUC). Conclusion LIA provides good postoperative analgesia which is similar to femoral block after total knee arthroplasty. The plasma concentration of ropivacaine seems to be below toxic levels in most TKA patients. The unbound plasma concentration of ropivacaine in THA seems to be below the toxic level. Implication The use of ketorolac in LIA may not be safer than other routes of administration, and similar restrictions should be applied in patients at risk of developing side effects.

Background Local infiltration analgesia (LIA) with local anaesthetic (ropivacaine), a nonsteroidal anti-inflammatory drug (ketorolac) and epinephrine after lower extremity arthroplasty has gained increasing popularity during the last decade. This method has certain advantages, which include minimal systemic side effects, faster post-operative mobilization, earlier post-operative discharge from hospital and less opioid consumption. However, information regarding plasma concentrations of ketorolac after LIA mixture is insufficient to predict the risk of renal impairment in patients subjected to arthroplasty. Aim To determine the maximal plasma concentration and the exposure of ketorolac during the first 30 h following LIA in hip arthroplasty. Methods Thirteen patients scheduled for primary total hip arthroplasty with LIA (ropivacaine 200 mg, ketorolac 30 mg and epinephrine 0.5 mg in a volume of 106 ml) were included. Plasma concentration of ketorolac was quantified by liquid chromatography-mass spectrometry. In addition, we assessed the effect of increasing age and decreasing glomerular filtration rate on the maximal plasma concentration and the total exposure to ketorolac during 30 h. Results The range of the maximal plasma concentration, 0.3–2.2 mg/l, was detected 30 min–4 h after completing the infiltration. Similar plasma levels have been reported after intramuscular injection of the same dose of ketorolac to healthy elderly volunteers. Conclusion Exposure to ketorolac after LIA may be comparable to an intramuscular injection of the same dose. Decision of dose reduction should be based on clinical assessment of risk factors.

In this study, we determined the plasma concentration of ropivacaine by liquid chromatography-mass spectrometry for 30 hours after local infiltration analgesia in 15 patients with elective hip arthroplasty. The 95% upper prediction bound of maximal unbound plasma concentration of ropivacaine was 0.032 mg/L. Side effects sufficient to stop an IV infusion have been reported at arterial concentrations of 0.34 to 0.85 mg/L. Alpha-1-acid glycoprotein did not correlate with the fraction of unbound ropivacaine during the first 24 hours after local infiltration analgesia. No signs or symptoms of systemic local anesthetic toxicity were observed. The Clopper-Pearson 95% upper confidence limit for adverse signs was 0.218.

Pain after total knee arthroplasty (TKA) is difficult to control. A recently developed and increasingly popular method for postoperative analgesia following knee and hip arthroplasty is Local Infiltration Analgesia (LIA) with ropivacaine, ketorolac and epinephrine. This method is considered to have certain advantages, which include administration at the site of traumatized tissue, minimal systemic side effects, faster postoperative mobilization, earlier postoperative discharge from hospital and less opioid consumption. One limitation, which may prevent the widespread use of LIA is the lack of information regarding plasma concentrations of ropivacaine and ketorolac. The aim of this academically initiated study was to detect any toxic or near-toxic plasma concentrations of ropivacaine and ketorolac following LIA after TKA. Methods Forty patients scheduled for primary total knee arthroplasty under spinal anaesthesia, were randomized to receive either local infiltration analgesia with a mixture of ropivacaine 300 mg, ketorolac 30mg and epinephrine or repeated femoral nerve block with ropivacaine in combination with three doses of 10mg intravenous ketorolac according to clinical routine. Plasma concentration of ropivacaine and ketorolac were quantified by liquid chromatography–mass spectrometry (LC–MS). Results The maximal detected ropivacaine plasma level in the LIA group was not statistically higher than in the femoral block group using the Mann–Whitney U-test (p = 0.08). However, the median concentration in the LIA group was significantly higher than in the femoral block group (p < 0.0001; Mann–Whitney U-test). The maximal plasma concentrations of ketorolac following administration of 30mg according to the LIA protocol were detected 1 h or 2 h after release of the tourniquet in the LIA group: 152–958 ng/ml (95% CI: 303–512 ng/ml; n = 20). The range of the plasma concentration of ketorolac 2–3 h after injection of a single dose of 10mg was 57–1216 ng/ml (95% CI: 162–420 ng/ml; n = 20). Conclusion During the first 24 h plasma concentration of ropivacaine seems to be lower after repeated femoral block than after LIA. Since the maximal ropivacaine level following LIA is detected around 4–6 h after release of the tourniquet, cardiac monitoring should cover this interval. Regarding ketorolac, our preliminary data indicate that the risk for concentration dependent side effects may be highest during the first hours after release of the tourniquet. Implication Femoral block may be the preferred method for postoperative analgesia in patients with increased risk for cardiac side effects from ropivacaine. Administration of a booster dose of ketorolac shortly after termination of the surgical procedure if LIA was used may result in an increased risk for toxicity.