Kristiina Kuusniemi

A low dose of plain or hyperbaric bupivacaine for unilateral spinal anesthesia.

Background and Objectives Unilateral spinal anesthesia may be advantageous, especially in the outpatient setting. A low dose of anesthetic solution, pencil-point needle, low speed of intrathecal injection, and a lateral position have been reported to facilitate the production of unilateral distribution of spinal anesthesia. We compared the effects of plain and hyperbaric bupivacaine in attempting to obtain a unilateral spinal anesthesia for patients undergoing outpatient knee arthroscopy. Methods Sixty patients were randomly allocated to 2 groups to receive either 1.2 mL (6 mg) of plain 0.5% bupivacaine (group 1; n = 30) or 1.2 mL (6 mg) of hyperbaric 0.5% bupivacaine in 8% glucose (group 2; n = 30). Drugs were administered at the L2-3 interspace with the patient in the lateral position. Patients remained in this position for 20 minutes before being turned supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale and compared between the operated and nonoperated sides. Results There was a significant difference between the operated and nonoperated side in both groups at all testing times, but a more unilateral spinal block was achieved with hyperbaric bupivacaine. Unilateral motor and sensory block was observed in 25 patients in group 2 (83%) and in 11 patients in group 1 (37%) (P < .01). The hemodynamic changes were minimal, since hypotension occurred only in 5.0% and bradycardia in 1.7% of all patients. Conclusion In conclusion, the spinal anesthesia in both groups are suitable alternatives for adult outpatient knee arthroscopies, but hyperbaric bupivacaine provides us with a more unilateral spinal block.

The Use of Bupivacaine and Fentanyl for Spinal Anesthesia for Urologic Surgery

We evaluated the effect of 25 &mgr;g of fentanyl added to bupivacaine on sensory and motor block. By using a double-blinded study design, 80 men undergoing urologic surgery were randomized into the following four groups: Group I, bupivacaine 10 mg; Group II, bupivacaine 10 mg + fentanyl 25 &mgr;g; Group III, bupivacaine 7.5 mg + fentanyl 25 &mgr;g; Group IV, bupivacaine 5 mg + fentanyl 25 &mgr;g. The final volume of intrathecal injectate was adjusted to 2.5 mL with sterile distilled water. Spinal anesthesia was administered with the 27-gauge Whitacre needle at the L2-3 interspace with the patient in the sitting position. Neural block was assessed by using pinprick and a modified Bromage scale. The degree of motor block was more profound in Group II compared with Group I at the end of operation. In Group IV, there was no motor block at the end of operation in any of the patients. The median level of the upper limit of the sensory block was higher than T7 in all groups before the start of surgery. The addition of 25 &mgr;g of fentanyl to 5 mg of bupivacaine resulted in short-acting motor block. When 25 &mgr;g of fentanyl was added to 10 mg of bupivacaine, it increased the intensity and duration of motor block. Only 5 (6.3%) of the patients needed supplemental analgesia during the operation. {abs} Implications Bupivacaine 5 mg with 25 &mgr;g of fentanyl for spinal anesthesia resulted in short-acting motor block. On the contrary, the addition of 25 &mgr;g of fentanyl to 10 mg of bupivacaine resulted in an increase in the motor block intensity and duration.

Plasma Concentrations of Oral Oxycodone Are Greatly Increased in the Elderly

We compared the pharmacokinetics of 10 mg oral oxycodone in four groups of 10 patients each, aged 20–40, 60–70, 70–80, and 80–90 years. Patients aged 70–80 and 80–90 years had 50–80% higher mean exposure to oxycodone (P < 0.05) and a twofold higher plasma oxycodone concentration (P < 0.05) than the young adults 12 h after ingestion of the drug. Because oxycodone pharmacokinetics depend to a great extent on the age of the subject, it is important to titrate the analgesic dose individually, particularly in the elderly.

Pharmacokinetics of Intravenous Paracetamol in Elderly Patients

Background and ObjectivesIntravenous paracetamol (N-acetyl-paraminophenol, acetaminophen) is a widely used nonopioid analgesic which has become popular in the treatment of pain in many patient groups, including the elderly. Although intravenous paracetamol has been studied widely in clinical analgesia studies, there is little information on its pharmacokinetics in the elderly. We designed this study to determine the pharmacokinetics of intravenous paracetamol in very old patients and to compare them with that of younger patients. We also considered the effect of adenosine triphosphate-binding cassette G2 protein (ABCG2) genotype and renal function on paracetamol pharmacokinetics in these patients.MethodsWe compared the pharmacokinetics of intravenous paracetamol in four groups of ten patients, aged 20–40, 60–70, 70–80 and 80–90 years, undergoing orthopaedic surgery. Paracetamol 1000 mg was given by infusion over 15 minutes. Plasma concentrations of paracetamol and its glucuronide and sulphate conjugates were measured for 24 hours with a high-performance liquid chromatographic method and ABCG2 genotype was determined. Glomerular filtration rate (GFR) was estimated from age, sex and serum creatinine of the patient.ResultsIn the group aged 80–90 years, the mean value of the area under the plasma concentration-time curve extrapolated to infinity (AUC∞) of paracetamol was 54–68% higher than in the two youngest groups. Paracetamol clearance showed a statistically significant dependence on age group, whereas volume of distribution during elimination and elimination half-life were associated with age group and sex, respectively. Based on mean AUC∞ of paracetamol glucuronide and paracetamol sulphate, the oldest patients had 1.3- to 1.5-fold greater exposure to these metabolites than patients aged 20–40 years. ABCG2 genotype did not affect paracetamol pharmacokinetics. There was a linear correlation between the values of AUC∞ of paracetamol, its glucuronide and sulphate metabolites and GFR.ConclusionAge and sex are important factors affecting the pharmacokinetics of paracetamol. The higher the age of the patient, the higher is the exposure to paracetamol. Female sex is associated with increased paracetamol concentrations but ABCG2 genotype does not seem to affect paracetamol pharmacokinetics.Trial registration number (EudraCT): 2006-001917-14

Elimination of intravenous oxycodone in the elderly: a pharmacokinetic study in postoperative orthopaedic patients of different age groups.

AbstractBackground and Objective: Oxycodone is a widely used opioid analgesic, the global use of which has increased several-fold during the last decade. This study was designed to determine the effect of age on the pharmacokinetics of intravenous oxycodone, with special reference to renal function in elderly patients. Methods: We compared the pharmacokinetics of 5 mg of intravenous oxycodone in four groups of 10–11 patients, aged 20–40, 60–70, 70–90 years, undergoing orthopaedic surgery. Plasma concentrations of oxycodone and its noroxycodone, oxymorphone and noroxymorphone metabolites were measured for 24 hours with a liquid chromatography-tandem mass spectrometric method. The cytochrome P450 (CYP) 2D6 genotype of the patients was determined. Glomerular filtration rate (GFR) was estimated on the basis of the age, sex and serum creatinine concentration of the patient. Results: The pharmacokinetics of oxycodone showed age dependency. In the oldest group, the mean area under the plasma concentration-time curve from time zero to infinity (AUC∞) of oxycodone was 80% greater (p < 0.001) and the apparent total body clearance of the drug from plasma (CL) was 34% lower (p < 0.05) than in the youngest group. The mean AUC∞ of oxycodone was also 30–41% greater in the oldest group than in the age groups of 60–70 and 70–80 years (p < 0.05). Oxycodone plasma concentrations from 8 hours post-dose were >2-fold higher (p < 0.01) in patients aged >80 years than in patients aged 20–40 years. Noroxycodone AUC∞ was increased in the oldest group compared with patients aged 20–40 and 60–70 years (p < 0.05). There were no significant sex-related differences in any of the pharmacokinetic parameters. Because 37 of the 41 patients were extensive metabolizers through CYP2D6, the effect of the CYP2D6 genotype on oxycodone pharmacokinetics could not be properly assessed. There was a linear correlation between GFR and CL (p < 0.01, coefficient of determination [r2] = 0.26), volume of distribution at steady state (p < 0.05, r2 = 0.19) and AUC∞ (p < 0.01, r2 = 0.29) of oxycodone. Conclusions: Age is an important factor affecting the pharmacokinetics of oxycodone. Following intravenous administration of oxycodone, patients aged >70 years are expected to have, on average, 40–80% higher exposure to oxycodone than young adult patients. Because oxycodone pharmacokinetics are greatly dependent on the age of the patient, it is important to titrate the analgesic dose individually, particularly in the elderly.

Low-dose bupivacaine : a comparison of hypobaric and near isobaric solutions for arthroscopic surgery of the knee

The results of studies on the effect of volume, concentration or total dose of local anaesthetic on the spread of spinal anaesthesia are inconclusive. Most support the assumption that the total dosage is more important than the volume. We compared low‐dose bupivacaine (6 mg) in 0.5% and 0.18% solutions as sole anaesthetic to achieve predominantly unilateral spinal anaesthesia for knee arthroscopy. Sixty patients were randomly allocated to two groups to receive either 1.2 ml 0.5% bupivacaine (6 mg) (n = 30) or 3.4 ml 0.18% hypobaric bupivacaine (6.1 mg) (n = 30). Drugs were administered at the L3–4 interspace with the patient in the lateral position. Patients remained in this position for 20 min before being turned supine for the operation. Spinal block was assessed by pinprick and modified Bromage scale and compared between the operated and nonoperated sides. No significant changes were found in the spread or duration of sensory or motor block (p > 0.05). The haemodynamic changes were also similar between the groups. The same pinprick level of analgesia, degree of motor block and duration of spinal anaesthesia was obtained with bupivacaine (6 mg) in low (1.2 ml) or high (3.4 ml) volumes.

Local infiltration analgesia with levobupivacaine compared with intrathecal morphine in total hip arthroplasty patients

Recently, local infiltration analgesia (LIA) has been promoted for pain control after total hip arthroplasty (THA). We hypothesized that LIA would offer equal analgesic efficacy but less adverse effects, e.g., nausea and vomiting, when compared with an established regimen [intrathecal morphine (it‐M)] after THA.

Prolonged-release Oxycodone/Naloxone in Postoperative Pain Management: From a Randomized Clinical Trial to Usual Clinical Practice:

Objective: These studies evaluated the feasibility of using oral prolonged-release oxycodone/naloxone (OXN PR) for the management of acute postoperative pain. Methods: Three studies were undertaken: (i) the analgesic efficacy of OXN PR was compared with prolonged-release oxycodone (OXY PR) in patients with knee arthroplasty in an immediate postoperative period (IPOP) study; (ii) OXN PR treatment was compared with other opioids during rehabilitation after knee arthroplasty in a noninterventional study (NIS); and (iii) surgical patients on other opioids were switched to OXN PR postoperatively during a quality improvement programme (QIP). Results: In the IPOP study, the pain intensity at rest score decreased by a similar amount in the OXN PR and OXY PR groups, indicating similar analgesic efficacies. In the NIS, patient assessments indicated enhanced efficacy and tolerability for OXN PR compared with other opioids. The QIP indicated significant improvements in bowel function and less difficulty passing urine at the end of OXN PR treatment compared with baseline. No safety concerns were raised. Conclusions: The analgesic efficacies of OXN PR and OXY PR were similar in postoperative pain settings. OXN PR reduced the degree of restriction in relation to patients carrying out physio - therapy compared with other opioids, and improved bowel and bladder function.

Inhibition of cytochrome P450 3A by clarithromycin uniformly affects the pharmacokinetics and pharmacodynamics of oxycodone in young and elderly volunteers.

The aim of this study was to investigate the effect of the cytochrome P450 3A4 inhibitor clarithromycin on the pharmacokinetics and pharmacodynamics of oral oxycodone in young and elderly subjects. Ten young and 10 elderly healthy subjects participated in this placebo-controlled, randomized, 2-phase crossover study. Subjects took clarithromycin 500 mg or placebo twice daily for 5 days. On day 4, subjects ingested an oral dose of 10 mg oxycodone. Plasma concentrations of oxycodone and its oxidative metabolites were measured for 48 hours, and pharmacological response for 12 hours. Clarithromycin decreased the apparent clearance of oxycodone by 53% in young and 48% in elderly subjects (P < 0.001) and prolonged its elimination half-life. The mean area under the plasma concentration-time curve (AUC0-∞) of oxycodone was increased by 2.0-fold (range, 1.3-fold to 2.7-fold) (P < 0.001) in young and 2.3-fold (range, 1.1-fold to 3.8-fold) (P < 0.001) in elderly subjects. The formation of noroxycodone was decreased by 74% in young and 71% in elderly subjects (P < 0.001). The ratio of AUC0-∞ of oxycodone during the clarithromycin phase compared with the one with placebo did not differ between the age groups. Clarithromycin did not alter the pharmacological response to oxycodone. Clarithromycin increased the exposure to oral oxycodone, but the magnitude of this effect was not age related. Although the pharmacological response to oxycodone was not significantly influenced by clarithromycin, dose reductions may be necessary in the most sensitive patients to avoid adverse effects when oxycodone is used concomitantly with clarithromycin.

Comparison of four pain scales in patients with hip fracture or other lower limb trauma.

Background: The applicability of the Visual Analogue Scale (VAS) has been questioned in the assessment of pain in the elderly. We compared VAS with three other pain scales, Verbal Rating Scale (VRS), Red Wedge Scale (RWS) and Box Scale (BS), in hip fracture patients.