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Biomedical subjects

E Kalso

Publications and source records attributed to E Kalso.

At least 73 records · Page 4Linked to original sources
PubMed1995

Controlled release of lidocaine from injectable gels and efficacy in rat sciatic nerve block.

PURPOSE: Methods of delaying the action of local anesthetics are important, since short duration of action limits their use in the treatment of postoperative and chronic pain. The present study evaluated the use of low-viscosity gels in prolonging the release of lidocaine. METHODS: Release of lidocaine from 2% lidocaine.HCl containing methylcellulose (MC), hydroxypropylmethylcellulose (HPMC), sodiumcarboxymethyl cellulose (CMC), and poloxamer 407 (PO) gels was studied in phosphate buffer, pH 7.4, at 37 degrees C. Commercial metylcellulose gel (MCcom) served as control. The in vivo efficacy of the respective gel formulations were evaluated in rats. The gel was injected into the vicinity of the sciatic nerve and nociception and motor function were tested. RESULTS: The cumulative amount of lidocaine released during 8 hr was slowest from the PO gel, followed by the CMC, HPMC and MC gels. The antinociceptive effect was not prevented by the motor block and lasted longest with the PO gel. Good linear and rank order correlation was obtained between in vitro and in vivo results. The microscopic examination of the tissue samples revealed only mild or no irritation of the skeletal muscle tissue by the PO, HPMC, and CMC gels. CONCLUSIONS: Based on these results poloxamer gel proved to be the most promising carrier for lidocaine.

Animals↗
PubMed1995

Extradural, paravertebral and intercostal nerve blocks for post-thoracotomy pain.

Forty-five patients were allocated randomly to receive either a single intrathoracic block of four intercostal nerves, a continuous thoracic extradural infusion or a continuous paravertebral infusion of bupivacaine. Patients were allowed additional i.v. boluses of morphine via a PCA device. Segmental spread of pinprick analgesia was comparable in the groups for up to 20 h. Up to 2 h after the block, plasma concentrations of bupivacaine were greater in the intercostal group and there was large interindividual variation. There were no significant differences between the groups in pain, morphine consumption, respiratory function or adverse events. Moderate to severe respiratory depression was detected in 14 patients more than 2 h after operation.

Adult↗
PubMed1995

Pain and other symptoms after different treatment modalities of breast cancer.

PURPOSE: The aim of this study was to analyse the risk factors that predispose women to chronic symptoms related to the treatment of breast cancer. PATIENTS AND METHODS: A questionnaire was sent to 569 women who had undergone modified radical mastectomies with axillary evacuation (MRM) or breast resection with axillary evacuation (BCT). RESULTS: Pain, paraesthesias and strange sensations were reported by half of the patients. The chronic pain slightly affected the daily lives of about 50% of the patients and moderately or more the daily lives of about 25% of the patients. Pain was reported significantly more often after BCT than after MRM both in the breast scar (BS) and in the ipsilateral arm (IA). The patients with chronic pain were significantly younger and had larger primary tumours. Postoperative complications increased the incidence of chronic pain in the IA. The highest incidence of pain in the IA was reported by patients who had had both radio- and chemotherapy. The fact that the incidence of pain (IA) had a significant correlation with the incidence of paraesthesias, oedema, strange sensations and muscle weakness may be an indication of nerve injury. CONCLUSIONS: Chronic pain was more common after breast-conserving surgery than after radical surgery. Surgical complications and postoperative radiotherapy and chemotherapy increased the risk of chronic pain and other symptoms. Modifications in the treatment protocol and preclusion of postoperative complications may be necessary in order to minimize chronic treatment-related symptoms.

Adult↗
PubMed1993

Intrathecal morphine-3-glucuronide does not antagonize spinal antinociception by morphine or morphine-6-glucuronide in rats.

Morphine or morphine-6-glucuronide either alone or in combination with morphine-3-glucuronide was administered intrathecally to rats. Antinociceptive effects were evaluated with the tail flick and the hot plate tests. Motor function was tested using the rotarod test. Estimated ED50 from the dose-response curves for morphine and morphine-6-glucuronide showed about a 30 times more potent antinociceptive effect of morphine-6-glucuronide compared with morphine. Morphine-3-glucuronide had no antinociceptive effect. Simultaneous administration of morphine-3-glucuronide 5.0 micrograms did not show any significant effect on antinociception induced by morphine 1.0 microgram or morphine-6-glucuronide 0.05 microgram.

Analgesics↗
PubMed1993

A review of oxycodone's clinical pharmacokinetics and pharmacodynamics.

Oxycodone (14-hydroxy-7,8-dihydrocodeinone) is a strong opioid agonist that is available alone or in combination with mild analgesics. It is suitable for oral administration due to high bioavailability (60%), and may also be given intramuscularly, intravenously, subcutaneously, and rectally; it is not recommended for spinal administration. In analgesic potency, oxycodone is comparable to morphine. With the exception of hallucinations, which may occur more rarely after oxycodone than after morphine, the side effects of these drugs are closely related. The abuse potential of oxycodone is equivalent to that of morphine. The usual indications for oxycodone are severe acute postoperative or posttraumatic pain and cancer pain. When oxycodone is administered, the same precautions should be taken as with morphine or other agonist opioids.

Biological Availability↗
PubMed1992

IV diclofenac in post-thoracotomy pain.

We have studied the efficacy of a continuous i.v. infusion of diclofenac 2 mg kg-1/24 h given for 2 days after major thoracic surgery in 30 patients in a double-blind, placebo-controlled, parallel-group design. The patients were able to obtain additional pain relief as on demand morphine boluses. In the diclofenac group, the consumption of morphine was reduced by 60% during the first and by 76% during the second day after operation compared with the control group. Overall, analgesia was also superior in the diclofenac group. Arterial oxygenation was significantly greater and the arterial PCO2 increased less during the first day after operation in the diclofenac group compared with the control group. Diclofenac had no significant effect compared with placebo on blood loss or on any bleeding or platelet test. Urine output was significantly less during the first day after operation in the diclofenac group compared with the control group, but was normal on the second day after operation; plasma creatinine concentrations were unchanged. I.v. diclofenac infusion combined with opioids delivered via a patient-controlled analgesia device seems a valuable method of pain relief after thoracic surgery in patients in whom more invasive techniques, such as extradural local anaesthetics and opioids, cannot be used. However, non-steroidal anti-inflammatory drugs should be used cautiously, if at all, in patients who are at risk of acute renal failure.

Adult↗
PubMed1992

The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects.

1. The pharmacokinetics and metabolism of oxycodone were studied in nine healthy young volunteers in a cross-over study. Each subject received oxycodone chloride once intramuscularly (0.14 mg kg-1) and twice orally (0.28 mg kg-1) at intervals of 2 weeks. A double-blind randomized pretreatment with amitriptyline (10-50 mg a day) or placebo was given prior to oral oxycodone. 2. The concentrations of oxycodone, noroxycodone and oxymorphone in plasma and the 24 h urine recoveries of their conjugated and unconjugated forms were measured by gas chromatography. 3. No differences were found between treatments in mean Cmax and AUC values of oxycodone which varied from 34 to 38 ng ml-1 and from 208 to 245 ng ml-1 h, respectively. The median tmax of oxycodone was 1 h in all groups. The bioavailability of oral relative to i.m. oxycodone was 60%. The mean renal clearance of oxycodone was 0.07-0.08 l min-1. The kinetics of oxycodone were unaffected by amitriptyline. 4. The mean ratio of the AUC(0.24 h) values of unconjugated noroxycodone to oxycodone was 0.45 after i.m. oxycodone and 0.6-0.8 after oral oxycodone. Plasma oxymorphone concentrations were below the limit of the assay. Eight to 14% of the dose of oxycodone was excreted in the urine as unconjugated and conjugated oxycodone over 24 h. Oxymorphone was excreted mainly as a conjugate whereas noroxycodone was recovered mostly in an unconjugated form.

Administration, Oral↗
PubMed1992

Pain after thoracic surgery.

In order to evaluate postoperative pain treatment following thoracic surgery, 214 medical records of patients who were operated during 1986-1988 were examined. Nurses' comments concerning pain and the amounts of analgesics given during the 2 postoperative days were recorded. The 150 patients who were still alive in December 1989 were sent a postal questionnaire which asked about the pain and the efficacy of pain relief they had received after their operation. They were also asked if they still had pain which they connected to the thoracotomy and if any attempts had been made to treat that pain. The mean consumption of intramuscular oxycodone was 38 mg during the 1st and 33 mg during the 2nd postoperative day. The administration of nonsteroidal anti-inflammatory drugs significantly reduced the opioid consumption on the second but not on the first postoperative day. In 30% of the patients' charts there were no remarks on pain, in 10% there was a mention of no pain, in 40% pain was mentioned and in 20% the patient was reported to have severe pain. During the first postoperative week little pain was experienced by 60% of the patients, considerable pain by 35% and excruciating pain by 5% of the patients being interviewed. The postoperative pain relief was rated as good in 60% of the answers, satisfactory in 38% and poor in 2%. Persistent post-thoracotomy pain lasting for more than 6 months was reported by 44% of the patients, of whom 66% had received treatment for the pain.

Acute Disease↗
PubMed1991

Involvement of supraspinal and spinal segmental alpha-2-adrenergic mechanisms in the medetomidine-induced antinociception.

The effect of systemically administered medetomidine, a selective alpha-2-adrenoceptor agonist, was studied by electrophysiological recordings of the peripherally evoked responses of three different types of sensory neuronal populations in the rat: medial thalamic neurons exclusively responding to mechanical cutaneous stimuli at noxious intensities, spinothalamic tract neurons of the spinal cord responding exclusively or differentially to mechanical cutaneous stimuli at noxious intensities, and low-threshold mechanoreceptive spinal dorsal horn neurons with ascending projections. The neuronal effects were compared with the behavioral data obtained in mechanically and thermally induced nociceptive tail reflex tests in intact and spinal rats. A reversal of the antinociceptive effects was attempted by systemically (1.5 mg/kg, i.p.) or intrathecally (25 micrograms) administered atipamezole, a selective alpha-2-adrenoceptor antagonist. Systemically administered medetomidine produced an atipamezole-reversible, dose-dependent suppressive effect on the evoked responses of nociceptive medial thalamic and spinothalamic tract neurons. A lower dose of medetomidine was needed to suppress significantly (half-maximally) evoked responses of the nociceptive medial thalamic neurons (100 micrograms/kg) than those of the nociceptive spinothalamic tract neurons (300 micrograms/kg). The decrease of evoked responses of the nociceptive spinothalamic tract neurons was accompanied by a decrease in spontaneous activity. The responses of the low-threshold mechanoreceptive projection neurons of the spinal cord were not influenced by medetomidine (30-300 micrograms/kg). The reflex studies with a (anesthetic) medetomidine dose of 300 micrograms/kg indicated that in intact and otherwise drug-free rats, medetomidine produced a significant prolongation of the nociceptive reflex response latency to a tail-pinch and heat; these antinociceptive effects of systemic medetomidine were reversed by systemically and intrathecally applied atipamezole. In spinal rats systemically applied medetomidine (300 micrograms/kg) also produced a significant prolongation of the tail-flick latency, which was reversed by systemically applied atipamezole. The results suggest that a high anesthetic dose of systemically applied medetomidine (300 micrograms/kg) can suppress nociceptive sensory neuronal and reflex responses due to spinal segmental mechanisms through an action on alpha-2-adrenoceptors. This spinal effect is selective to responses of nociceptive neurons, and at least partly postsynaptic as indicated by the concomitant decrease in spontaneous activity. At a lower, subanesthetic (but sedative) dose (100 micrograms/kg) the antinociceptive effect of systemically applied medetomidine can be explained by supraspinal alpha-2-adrenergic mechanisms.

Adrenergic alpha-Agonists↗
PubMed1991

Sensitivity, specificity and predictive value of the sensation of warmth as a method of detecting inadvertent subarachnoid injection of local anaesthetic when performing extradural blocks.

In order to test if the rate of onset of sensation of warmth in the legs after the injection of 0.5% bupivacaine might discriminate between subarachnoid and extradural injection, 150 urological patients were allocated randomly to receive either spinal anaesthesia with isobaric (IS) or hyperbaric (HS) 0.5% bupivacaine, or extradural anaesthesia with isobaric 0.5% bupivacaine. The volume of the local anaesthetic for spinal anaesthesia and for the extradural test dose was 3-4 ml. The patients were asked to report at once if they had a sensation of warmth in the legs during or after injection of local anaesthetic. The mean time to the sensation of warmth was significantly shorter in the spinal groups (80 (SEM 10) s in IS and 76 (8.0) s in HS) than in the extradural group (558 (38) s). However, six patients in the IS and two in the HS group had no sensation of warmth.

Adult↗
PubMed1991

The pharmacokinetics of oxycodone after intravenous injection in adults.

Oxycodone chloride (0.07 mg kg-1) was given by intravenous bolus to nine young adult surgical patients on the first postoperative day. Plasma was sampled for up to 12 h. Mean values of t1/2z, CL and Vss were 222 min, 0.78 l min-1 and 2.60 l kg-1, respectively. The concentrations of the metabolite noroxycodone was also measured. The mean AUC(0,12) ratio of noroxycodone to oxycodone was 0.33. Oxymorphone was not detected.

Adult↗
PubMed1991

Intravenous morphine and oxycodone for pain after abdominal surgery.

Intravenous morphine and oxycodone were given double blind in doses of 0.05 mg/kg after major abdominal surgery to 39 patients. The dosing interval was 5 min, until the patient did not want any further analgesics. Less oxycodone was needed than morphine, both to achieve the "first state of pain relief" (13.2 mg vs. 24.9 mg) and during the whole 2-h study period (21.8 mg vs. 34.2 mg). The "first state of pain relief" was achieved faster (28 min vs. 46 min) and lasted longer (39 min vs. 27 min) with oxycodone than morphine. Morphine caused more sedation and a greater decrease in the mean arterial blood pressure than oxycodone. In other respects the two opioids were comparable.

Abdomen↗
PubMed1991

The uptake of bupivacaine in an in situ isolated perfused rabbit lung preparation.

A double indicator technique has been used in an in situ isolated perfused rabbit lung model to examine the first pass effect of the lung on systemic bupivacaine concentrations. Bupivacaine (0.5 mg/kg) was given in two consecutive boluses to six in situ isolated perfused New Zealand White rabbit lung preparations. The mean recovery (first bolus) of bupivacaine was 62.6% +/- 6.3 (S.E.M.), and 63.7% +/- 10.2 (second bolus), suggesting bupivacaine accumulation in the lung. The average mean transit time for bupivacaine was 280.5% +/- 24.1 and 264.8% +/- 36.7 longer than ICG (Indocyanine Green) following the first and second boluses respectively (P less than 0.01). There were no differences in the first pass effect of the lung between the first and second boluses of bupivacaine. The profiles of the bupivacaine concentrations suggest that uptake is followed by accumulation and later back diffusion. This has implications for conditions that decrease the uptake and therefore increase the risk of systemic toxicity.

Animals↗
PubMed1990

Morphine and oxycodone hydrochloride in the management of cancer pain.

In a double-blind crossover study, morphine and oxycodone hydrochloride were administered to 20 patients who were experiencing severe cancer pain. The peroral doses were determined on the basis of patient-controlled intravenous titration. The assumed oral bioavailability ratios were 44% (group 1, first 10 patients) and 33% (group 2, last 10 patients) for morphine and 66% (group 1) and 50% (group 2) for oxycodone hydrochloride, respectively. However, the patients were able to readjust their oral dosings. Equal analgesia was achieved with both drugs, but the intravenous dose of oxycodone hydrochloride needed was 30% higher than that of morphine. The median calculated oral/intravenous ratios giving comparable analgesia were 0.31 for morphine and 0.70 for oxycodone hydrochloride. Morphine caused more nausea than oxycodone hydrochloride and hallucinations occurred only during morphine treatment. Otherwise, there were no major differences in the side effects between these two opioids.

Administration, Oral↗
PubMed1990

Morphine and oxycodone in the management of cancer pain: plasma levels determined by chemical and radioreceptor assays.

Morphine and oxycodone were administered to ten patients suffering from severe cancer pain in a double-blind cross-over study. The patients titrated themselves pain-free, first intravenously, using a patient-controlled analgesia device, and then orally. Each titration phase lasted for 48 hours. Blood samples were drawn after 36 hr of each administration phase. The plasma levels of morphine, morphine-6- and morphine-3 glucoronides were determined with high performance liquid chromatography (HPLC), whereas the oxycodone samples were assayed with gas chromatography (GC). Twin samples were analyzed for plasma opioid activity with a radioreceptor assay (RRA) using 3H-dihydromorphine and 3H-naloxone as radioligands. Adequate analgesia was achieved with both morphine and oxycodone. About 30% more oxycodone was needed intravenously, whereas 25% less oxycodone than morphine was consumed orally. There was a good linear correlation between the morphine concentrations measured with HPLC and RRA. The mean morphine-6-glucuronide to morphine concentration ratio was 2.3 after intravenous and 4.6 after oral administration. Results from RRA indicate that oxycodone in vivo is a potent mu-agonist and that at least part of its analgesic action is mediated by active metabolites. In vitro morphine glucuronides enhanced morphine in displacing radioligands from the opioid receptors, thus suggesting their complex interactions in vivo.

Administration, Oral↗