Muscarinic receptors in equine airways.

The distribution of muscarinic receptors in equine airways was investigated using autoradiography. Frozen sections of tissue from six different levels in the bronchial tree, from the trachea to the distal bronchioles, were incubated in vitro with 1.5 nmol/L of the muscarinic receptor antagonist 1-[N-methyl-3H]scopolamine methyl chloride (3H-NMS). In addition, the subtype pattern of muscarinic receptors was investigated in equine tracheal smooth muscle using radioligand binding with methoctramine, tripinamidc, 4-DAMP-methiodide and pirenzipine as competitors against the binding of 1.3 nmol/L 3H-NMS. The autoradiograms showed specific labelling indicating a high density of muscarinic receptors in smooth-muscle tissue in all levels of the airway tree investigated. Besides muscle tissue, subepithelial glands were the only structures specifically labelled. The dominating subtypes in tracheal smooth muscle investigated with radioligand binding studies were found to be M2 and M4, as both methoctramine (pKd = 8.5) and tripinamide (pKd = 8.6 and 6.7 for two different sites) showed high affinity. The density of the M3-muscarinic receptor subtype was low, but this subtype could be detected with statistical significance when methoctramine was used as the competitor against 3H-NMS binding.

Remifentanil and fentanyl during anaesthesia for major abdominal and gynaecological surgery. An open, comparative study of safety and efficacy.

BACKGROUND: and objective This open, multicentre study compared the efficacy and safety of remifentanil with fentanyl during balanced anaesthesia with 0.8% isoflurane (end-tidal concentration) for major abdominal and gynaecological surgery, and the efficacy and safety of remifentanil for pain management in the immediate postoperative period. METHODS: Two-hundred and eighty-six patients were randomized to receive remifentanil 1 microg kg(-1) followed by 0.2 microg kg(-1) min-1 (n=98), remifentanil 2 microg kg(-1) followed by 0.4 microg kg(-1) min(-1) (n=91) or fentanyl 3 microg kg(-1) (n=97) at induction. Thereafter, the study opioids and isoflurane were titrated to effect during the operation. RESULTS: Compared with fentanyl, remifentanil 2 microg kg(-1) followed by 0.4 microg kg(-1) min(-1) reduced the incidence of response to tracheal intubation (30% vs. 13%, P < 0.01), skin incision (33% vs. 4%, P < 0.001) and skin closure (11% vs. 3%, P < 0.05), respectively. Patients receiving remifentanil 1 microg kg(-1) followed by 0.2 microg kg(-1) min(-1) had fewer responses to skin incision than the fentanyl group (12% vs. 33%, P < 0.001), but the incidences of response to tracheal intubation and skin closure were similar. Significantly fewer patients in both remifentanil groups had > or = 1 responses to surgical stress intraoperatively compared with fentanyl (68% and 48% vs. 87%, P < 0.003). The mean isoflurane concentrations required were less in both remifentanil groups compared with the fentanyl group (0.1%, P=0.05). In remifentanil-treated patients, continuation of the infusion at 0.1 microg kg(-1) min(-1) with titration increments of +/- 0.025 microg kg(-1) min(-1) was effective for the management of immediate postoperative pain prior to transfer to morphine analgesia. However, a high proportion of patients experienced at least moderate pain whilst the titration took place. CONCLUSIONS: Anaesthesia combining isoflurane with a continuous infusion of remifentanil was significantly more effective than fentanyl at blunting responses to surgical stimuli. Significantly fewer patients responded to tracheal intubation with remifentanil at 0.4 microg kg(-1) min(-1), supporting the use of a higher initial infusion rate before intubation. Both remifentanil and fentanyl were well-tolerated, with reported adverse events typical of mu-opioid agonists.

Pharmacokinetics and pharmacodynamics of terbutaline in healthy horses.

OBJECTIVE: To determine pharmacokinetics of terbutaline in healthy horses and to relate serum terbutaline concentrations with the drug's pharmacodynamic effects. ANIMALS: 6 healthy horses. PROCEDURE: Horses were given terbutaline i.v. (10 microg/kg of body weight) and, 1 week later, p.o. (100 microg/kg). Responses to drug administration (eg, heart rate and serum lactate concentration) were measured. Serum terbutaline concentration was measured by means of gas chromatography with mass spectrometry. Protein binding was determined in vitro. RESULTS: Following i.v. administration, median maximum serum terbutaline concentration and mean residence time were 9.3 ng/ml and 30 minutes, respectively. Bioavailability following oral administration was < 1%. All horses developed sweating, trembling, excitement, and tachycardia during i.v. infusion. The 2 horses with the highest serum terbutaline concentrations developed severe tachycardia and CNS stimulation; 30 minutes after the i.v. infusion was completed, they were hyperventilating and lethargic. Heart rate and serum lactate concentration increased as serum terbutaline concentration increased. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that terbutaline is rapidly cleared from the bloodstream following i.v. administration to horses, suggesting that continuous i.v. infusion would be needed to maintain therapeutic serum concentrations. Oral administration of terbutaline to horses is not practical because of the low bioavailability.

Melanin affinity: a possible explanation of isoxsuprine retention in the horse.

Isoxsuprine is used in veterinary medicine as a vasodilating agent. The drug has been detected in the urine of horses up to 6 weeks after the cessation of administration. In the present study, the distribution pattern of 3H-isoxsuprine was investigated using whole body autoradiography in mice to find a possible site of retention. Melanin was the only place of retention identified. Additional in vitro studies showed an affinity of isoxsuprine to both melanin and keratin. The K(d) values were 0.02 mmol/l and 1 mmol/l, and the B(max) values were 0.2 micromol/mg and 2 micromol/mg, respectively. A low affinity site with approximately the same K(d) and B(max) as keratin was also detected for melanin. 3H-isoxsuprine was found to have affinity to pigmented horse skin after incubation in vitro and microautoradiography. We believe that affinity to melanin and possibly also to keratin can cause retention of the drug in the body and therefore explain the prolonged excretion of low levels of isoxsuprine in the horse.

Intrathecal infusion of bupivacaine with or without buprenorphine relieved intractable pain in three patients with vertebral compression fractures caused by osteoporosis.

BACKGROUND AND OBJECTIVES: At present, there is no reliable method of relieving "refractory" pain in patients with compression fractures of the vertebral bodies caused by osteoporosis. We explored the possibility of relieving this type of pain by intrathecal (i.t.) infusion of bupivacaine with or without buprenorphine. METHODS: An 18-g nylon i.t. catheter was inserted via a lumbar interspace with its tip positioned at the level of the fractured vertebra from which the maximal pain originated. Bupivacaine (2.375-5.0 mg/mL) with (n = 1) or without (n = 2) buprenorphine (0.015 mg/mL) was infused through the i.t. catheter from an external electronic pump. The infusion began in the operating room at a basic rate of 0.1-0.2 mL/h, with optional bolus doses (0.1 mL, 1-4 times/h) via patient controlled analgesia. The daily dose of i.t. bupivacaine was adjusted to provide satisfactory pain relief [visual analogue scores (VAS) = 0-2 on a scale of 0-10]. RESULTS: Satisfactory pain relief was obtained with daily doses of i.t. bupivacaine ranging from 10 to 70 (mean approximately 25) mg and buprenorphine from 0.02 to 0.2 (mean = 0.15) mg. The duration of i.t. treatment was 37, 387, and 407 days, respectively. Two patients terminated the i.t. treatment when it was no longer needed. Treatment was discontinued in the third patient because of death caused by irreversible heart failure. The 2 surviving patients were still free of pain 1,074 and 1,476 days after termination of the i.t. treatment. No severe complications occurred. CONCLUSIONS: Continuous intrathecal infusion of bupivacaine, with or without buprenorphine, appeared to be an effective method for the long-term treatment (months to > 1 year) of "refractory" pain from vertebral compression fractures, in this small group of patients.

Clinical experience using intrathecal (IT) bupivacaine infusion in three patients with complex regional pain syndrome type I (CRPS-I).

BACKGROUND AND AIM: To date, there is no reliable method for treating the severe pain and for modifying the natural evolution of CRPS-I. Therefore, we explored the effect of long-term IT bupivacaine infusion (with or without buprenorphine) on this syndrome. PATIENTS AND METHODS: (a) PATIENTS: two women and one man, 25, 31 and 42 years old, with CRPS-I of the lower (n=2) or upper (n=1) extremity lasting for 4 and 5 months, and 14 years. (b) INTERVENTIONS: insertion of externalized IT catheters; IT infusion of buprenorphine 0.015 mg/ml and bupivacaine 4.75 mg/ml (n=1), or only bupivacaine 5 mg/ml (n=2) from external electronic pumps. RESULTS: The IT treatment lasted for 172, 282 and 668 days. The mean/maximal daily doses of the IT bupivacaine were 39/66, 55/80 and 69/125 mg, respectively. The pain intensity decreased from VASmean =7+/-1 to VASmean =2+/-2. None of the patients had regression of allodynia, edema, and trophic disturbances in the affected extremities. In 2 patients, the IT treatment did not prevent spread of the disease to the opposite extremity or the occurrence of phantom pain and stump allodynia after amputation. The IT catheters were withdrawn as being no longer needed: in 2 patients 56 and 458 days after amputation of the involved extremity, and in another one before replacement of the IT bupivacaine infusion with epidural dorsal column stimulation (EDCS). After termination of the IT treatment, the patients were observed for 1437, 1575, and 2689 days (until September 1, 1998). At that date, all the patients were alive, and still affected by their CRPS-I, either in the amputation stump (n=2), and/or in the opposite or remote extremities (n=2); further, two were unemployed and one worked for 75% of the time. One of them was taking up to 1500 mg of slow-release morphine to cope with pain. CONCLUSION: The IT pain treatment with bupivacaine (with or without buprenorphine) alleviated the "refractory" pain, but affected neither the associated symptoms and signs of the CRPS-I, nor its natural evolution. Thus, the IT treatment cannot be recommended in preference to other pain treatment regimens for CRPS-I.

Progressive systemic sclerosis: intrathecal pain management.

BACKGROUND AND OBJECTIVES: At present, there is no reliable method for long-term treatment of severe pain from progressive systemic sclerosis (PSS) associated with Raynaud's phenomena leading to ischemia and ulcerations of the extremities. Long-term continuous intrathecal (IT) buprenorphine/bupivacaine analgesia was used in such a case. METHODS: The patient was a 71-year-old woman in whom conservative treatment, including opioids, dorsal column stimulation, and epidural bupivacaine, had failed to provide satisfactory, long-term relief for her severe lower extremity pain. An 18-gauge Portex intrathecal catheter was inserted via the L4-L5 interspace. An infusion of 4.75 mg/mL bupivacaine and 0.015 mg/mL buprenorphine was started from a portable Pharmacia-Deltec (St. Paul, MN) pump at a rate of 0.1 mL/h with optional bolus doses of 0.1 mL, 2-4 times/h by patient controlled intrathecal analgesia. The rate was adjusted to give the patient satisfactory (80-100%) pain relief. RESULTS: The IT treatment was continued with 0.1 mL (approximately 0.5 mg/h bupivacaine) for most of the time (mean dose = 18.6 mg/d). This treatment gave the patient 90-100% pain relief, which subsequently improved the quality of her life. Nocturnal sleep duration increased from 2 hours before to 7-8 hours during the IT treatment. The treatment was complicated by transient post-dural puncture headache and further by meningitis, successfully treated with parenteral and intrathecal antibiotics. Every attempt to increase the IT bupivacaine to >20 mg/d led to transient urinary retention, paresthesia, and reduced motor strength in the lower extremities accompanied by gait disturbances. The IT treatment lasted for 861 days (of which 580 days were spent at home), until the patient's death, not related to the treatment. CONCLUSION: Intrathecal infusion of buprenorphine/bupivacaine provided satisfactory long-term pain relief in a patient with PSS-associated Raynaud's phenomena, skin ulcerations, and intractable ischemic pain.

A comparison between clenbuterol, salbutamol and terbutaline in relation to receptor binding and in vitro relaxation of equine tracheal muscle.

Beta2-adrenoceptor agonists are used as bronchodilators in both humans and horses. Of these drugs, clenbuterol is the one most frequently used when treating chronic obstructive pulmonary disease in the horse, while salbutamol and terbutaline are used in the treatment of human asthma. Little is known of the properties of the latter two drugs in equine medicine. We have compared salbutamol and terbutaline with clenbuterol in relation to their ability to relax muscle strips from equine tracheal muscle, precontracted with 40 nM carbachol, in tissue chambers. The affinities of these drugs to the beta2-adrenoceptors in homogenates of the same muscle tissue were also examined. These experiments were performed with radioligand binding studies using the very potent beta-adrenoceptor antagonist 125I-cyanopindolol. The three drugs were almost equipotent in relaxing the muscle strips. The EC50-values for salbutamol, terbutaline and clenbuterol were 5.6, 13.8 and 2.1 nM, respectively, and all three drugs relaxed the preparations completely. In the competitive binding study, however, the Kd-value of clenbuterol was much lower (24 nM) than that of salbutamol and terbutaline (1100 nM and 3900 nM, respectively). The amount of receptors bound at the EC50-value of clenbuterol was 8% compared to less than 1% for salbutamol and terbutaline. This indicates a lower intrinsic efficacy of clenbuterol than of the other two drugs. The beta-adrenoceptor density was 45 +/- 14.3 fmol/mg protein (mean +/- SD) and the Kd-value of 125I-cyanopindolol was 11.4 +/- 3.3 pM.

High thoracic/low cervical, long-term intrathecal (i.t.) infusion of bupivacaine alleviates "refractory" pain in patients with unstable angina pectoris. Report of 2 cases.

BACKGROUND: There is no reliable treatment for "refractory" pain from unstable angina pectoris (UAP) when epidural infusion of bupivacaine has failed to relieve it. In two such cases we explored the potential of intrathecal (i.t.) bupivacaine infusion to provide pain relief. PATIENTS AND METHODS: Two female patients, 70 and 67 years. An 18-G nylon catheter was inserted intrathecally through a 17-G Tuohy needle via the T2-T3 interspace and its tip located at the height of C6-C7 vertebrae. The catheter was connected to a portable, programmable electronic pump filled with bupivacaine 5 mg/ml. The infusion started at rates of 0.1-0.2 ml/h, with optional bolus doses of 0.1-0.2 ml, 4-2 times/h, respectively, by PCA (Patients-Controlled Analgesia), and then adjusted to give the patients satisfactory (80%-100%) pain relief. RESULTS: Pain relief was obtained with doses of i.t.-bupivacaine ranging from 17 to 45 (mean = 25) mg/d. The pain intensity decreased from VAS (Visual Analogue Score) 9-10 to 0-2 out of 10. The nocturnal sleep improved from 2-4 to 6-7 h. The patients could now ambulate, walking or in a wheel-chair. The i.t.-treatment lasted 700 and 437 d, of which 540 and 343 d (respectively) were spent at home, and was terminated by: (a) the patient's death due to intracranial bleeding (1st case); (b) progressive aggravation of the unstable angina that could not be fully countered by increasing the bupivacaine dose above 1.0 mg/h due to occurrence of cerebral transient ischemic attacks, usually not correlated with orthostatic arterial hypotension but apparently facilitated by microembolization of the cerebral arteries (2nd case). CONCLUSION: I.t.-bupivacaine infusion may alleviate "refractory" pain in patients with unstable angina pectoris when epidural bupivacaine failed to do so. Its use is apparently limited by the IT-bupivacaine critical dosage (in these patients = 1.0-1.5 mg/h).

Six years of continuous intrathecal infusion of opioid and bupivacaine in the treatment of refractory pain due to intrapelvic extrusion of bone cement after total hip arthroplasty.

BACKGROUND AND OBJECTIVES: There is at present no reliable method for long-term treatment of severe pain following complications of total hip arthroplasty. We explored the long-term use of continuous intrathecal opioid/bupivacaine analgesia in a case not amendable to corrective surgery. METHODS: A 77-year-old woman, having a total hip arthroplasty, developed refractory nociceptive-neuropathic pain located at the ventral and dorsal aspects of the left hip. Radiographs showed a mandarine-sized intrapelvic mass of bone cement adhering to the roof of the acetabular cup. Further surgery had been declined by the surgeon and by the patient. An 18-gauge Portex intrathecal catheter was inserted, and an intrathecal infusion of 4.75 mg/mL bupivacaine and 0.015 mg/mL buprenorphine was started from a portable Pharmacia-Deltec (St. Paul, Minnesota) pump. RESULTS: The mean daily doses during the treatment period (more than 6 years up to now) were 37 mg for bupivacaine and 0.114 mg for buprenorphine. The intrathecal treatment gave the patient 85-100% pain relief. The patient could transport herself in a wheelchair, was able to perform her own hygiene, receive visits, read, watch television, and also shop and visit restaurants. There has been no need to replace the intrathecal catheter. CONCLUSION: Intrathecal infusion of opioid/bupivacaine can provide satisfactory long-term analgesia in patients with refractory pain from the hip joint.

Continuous infusion of opioid and bupivacaine by externalized intrathecal catheters in long-term treatment of "refractory" nonmalignant pain.

OBJECTIVE: To explore the possibility of obtaining pain relief by continuous intrathecal infusion of bupivacaine and opioid in patients with intractable nonmalignant pain. DESIGN: Prospective, cohort, nonrandomized, consecutive trial. SETTING: Tertiary care center, institutional practice, hospitalized, and ambulatory care. PATIENTS: A total of 90 patients, 40 men and 50 women, 20 to 96 years old (median, 70 years), with various nonmalignant "refractory" pain conditions lasting for 0.3 to 50 years (median, 3 years) with nociceptive (n = 9), neurogenic/neuropathic (n = 17), and mixed pain (n = 64) were consecutively included in the study when (a) the pain dominated their lives totally, (b) other methods failed to provide acceptable pain relief, and (c) unacceptable side effects from opioids had occurred. Moribund patients and those with overt psychoses at the time of the assessment were excluded from the study. INTERVENTIONS: (a) Insertion of externalized, tunnelled intrathecal catheters (101 in 90 patients). (b) Intrathecal infusion of opioid (morphine 0.5 mg/ml, or buprenorphine 0.015 mg/ml, and/or bupivacaine 4.75-5.0 mg/ml) from external electronic pumps was started in the operating room at a basic rate of 0.2 ml/hour, with optional bolus doses (0.1 ml 1-4 times/hour) by patient-controlled analgesia (PCA). Thereafter, the daily volumes were tailored to give the patients satisfactory to excellent (60-100%) pain relief, with acceptable side effects from the infused drugs, by increase or decrease of the basic rates and/or of the bolus doses, and their timing. (c) Supervision of the patients for 24 hours after catheterization in the postoperative ward. (d) Daily phone contact with the patients, their families, or the nurses in charge. (e) The patients had ad libitum access to nonopioid analgesics/sedatives and to opioids administered by various routes, until they obtained satisfactory pain and anxiolytic relief. MAIN OUTCOME MEASURES: (a) Pain intensity (visual analog scores 0-10) and pain relief (0-100%). (b) Daily dosages (opioid administered by intrathecal and other routes, and intrathecal bupivacaine). (c) Scores (0-5) of nonopioid analgesics, gait and ambulation, duration of nocturnal sleep, and (d) rates of adverse effects. RESULTS: During the intrathecal period [range, 3-1,706 days; median, 60 days; totaling 14,686 days, 7,460 (50% of which were spent at home)], 86 patients (approximately 95%) obtained acceptable (60-100%) pain relief. The nocturnal sleep duration increased from <4 to 7 hours (median values), nonopioid analgesic and sedative daily consumption became approximately two times lower, whereas the gait ability and ambulation patterns remained practically unchanged. Five patients still had ongoing treatment after durations of 30 to 1,707 (median, 206) days at the close of the study. In the remaining 85 patients, the intrathecal treatment was terminated because of patients' death (n = 23), replacement of the intrathecal treatment by dorsal column stimulation (n = 1), pain resolution (n = 32), refusal to continue the intrathecal treatment (n = 19), lack of cooperation due to delirium or to manipulation of the pump (n = 8), and loss of efficacy of the intrathecal treatment (n = 2). Thus, in the long run, the intrathecal treatment failed in 29 of the 85 patients with terminated treatment (34%). The principal side-effects and complications, except those attributed to the dural puncture, the equipment, and the long-term catheterization of the subarachnoid space, which are presented separately, were severe bradypnea (n = 1), transient paresthesiae (n = 26), short-lasting pareses (n = 16), temporary urine retention (n = 34), episodic orthostatic arterial hypotension (n = 11), and attempted suicide (n = 5, 3 of which were successful). No neurologic sequelae or death could be attributed to the intrathecal procedure. (ABSTRACT TRUNCATED)

Efficacy and technical complications of long-term continuous intraspinal infusions of opioid and/or bupivacaine in refractory nonmalignant pain: a comparison between the epidural and the intrathecal approach with externalized or implanted catheters and infusion pumps.

OBJECTIVE: To compare efficacies, failure rates, and technical complication rates of intraspinal treatments in patients with "refractory" nonmalignant pain conditions in relation to the approach (epidural/intrathecal), the drug (opioid/opioid-bupivacaine or bupivacaine), and the type of system used (externalized/internalized). In these comparisons, recent data from a companion paper (Nitescu et al., Clin J Pain 1998;14:17-28) were used as a reference to be compared with data from a literature review of different intraspinal treatment modalities in nonmalignant pain. DESIGN: Prospective, cohort, nonrandomized, consecutive trial. SETTING: Tertiary care center, institutional practice, hospitalized, and ambulatory care. PATIENTS: Five groups according to treatment modality: (a) externalized, long-term intrathecal nylon catheters, connected to external, electronic infusion pumps (companion paper), n = 90; (b) internalized, long-term intrathecal catheters (Silastic) connected to implanted SynchroMed pumps, n = 330 (literature review); (c) externalized, "short-term" epidural catheters for "temporary" infusions, n = 565 (literature review); (d) externalized, long-term epidural catheters, n = 50 (literature review); (e) internalized, long-term epidural catheters, n = 111, connected to implanted systems: Port-A-Cath injection ports, n = 58; Infusaid pumps, n = 46; and SynchroMed pumps, n = 7 (literature review). INTERVENTIONS: In reviewing the literature, we found 21 studies that reported on the intraspinal (epidural or intrathecal) administration of opioids with or without local anesthetics (usually bupivacaine). These studies were analyzed with respect to the rates of the variables satisfactory pain relief (efficacy), failures, and technical complications. A rate is the number of observations of a variable divided by the number of patients or the number of catheters or infusion systems, as logically indicated (e.g., the numbers of complications, such as epidural abscess and meningitis, were related to the number of patients and those of catheter occlusion or leakage to the number of the catheters). The variables were expressed as the means of the rates of a variable from studies belonging to various treatment modalities: approach (epidural vs. intrathecal), duration (short vs. long term), drugs administered intraspinally (opioid vs. opioid and/or local anesthetic), and type of infusion system (externalized vs. internalized). Further, the sums of all observations of one variable in different studies with various treatment modalities were related to the corresponding sums of the patients (alternatively, catheters or implanted devices). The proportions of these sums were tested for significance in relation to treatment modality. MAIN OUTCOME MEASURES: Comparative rates of successful intraspinal treatment and its failures and complications. RESULTS: (a) The intrathecal approach, compared with the epidural approach, was associated with higher rates of satisfactory pain relief for both externalized (86/90, 95% vs. 17/40, 42.5%, p < .0001) and internalized (295/336, 89% vs. 33/56, 59%, p < .0001) catheters; higher rates of treatment failures with externalized epidural catheters than with internalized intrathecal catheters (24/47, 51%, vs. 36/338, 11%, p < .0001); lower rates of treatment failures with internalized intrathecal catheters than with internalized epidural catheters (36/338, 11% vs. 29/76, 38%, p < .0001); higher rates of system replacement with internalized epidural catheters than with internalized intrathecal catheters (23/32, 72% vs. 6/49, 12%, p < .0001; higher rates of system removal with internalized epidural catheters than with internalized intrathecal catheters (22/49, 45% vs. 5/49, 10%, p < .001); higher rates of catheter-related complications with epidural than with intrathecal catheters (dislodgement 13/126, approximately 10% vs. 6/150, 4%, p < .05; leakage 5/51, approximately 10% vs. 1/116, 0.9%, p < .05; obstruction 2

[Severe pain relief with intrathecal infusion. The patient controls, treatment can be provided at home]. / Svår smärta lindras med intratekal infusion. Patienten styr, behandlingen kan ges i hemmet.

Intrathecal administration of an opioid such as morphine in combination with a local anaesthetic such as bupivacaine is an effective treatment for severe cancer pain. The treatment, which can often be made available in the patient's home, provides relief from pain without unwanted sedation, when high-dose oral or parenteral morphine no longer has any effect. The patient controls the treatment, and can achieve a balance between pain relief and side-effects. The article outlines the routines established at the pain unit at Sahlgrenska Hospital in Gothenburg.

Continuous intrathecal infusion of opioid and bupivacaine in the treatment of refractory pain due to postherpetic neuralgia: a case report.

This report details the course of a 77-year-old patient suffering mild pain from operated tongue cancer and excruciating, intractable pain from thoracic (T6-T8) post-herpetic neuralgia (PHN), The mouth pain was treated with nonopioid analgesics, as the patient had personal objections to opioid treatment. All the components of the pain from his PHN (continuous burning pain, intermittent lancinating stabbing pain, and tactile allodynia) were successfully treated with an Intrathecal Infusion of buprenorphine (0.03 mg/ml) and bupivacaine (4.75 mg/ml) administered via an externalized intrathecal catheter with the tip located at T9-T10 intervertebral disc. The treatment started three months after the appearance of the herpetic eruption and lasted 294 days until the patient died of malnutrition and the progression of his tongue cancer. During treatment, he experienced satisfactory pain relief from his PHN; the mean visual analogue scores (VASmean), recorded on a scale from 0 to 10, ranged from 1 to 2, compared to 9 to 10 before starting the intrathecal treatment. Analgesia was established with 0.2-0.315 mg/day of intrathecal buprenorphine and 90-100 mg/day of intrathecal bupivacaine. His undisturbed nocturnal sleep increased from 4 to 5-6 hours. The side-effects from the bupivacaine (urine retention requiring insertion of an indwelling urinary catheter, paresthesias, and mild pareses) were recorded. The patient could ambulate without support while on 90-100 mg/day of intrathecal bupivacaine. During a series of high-pressure oxygen treatments in a pressure chamber to treat an infection at the site of his tumor, the intrathecal infusion was interrupted. Thus, repeated observation of the intervals of severe pain and of analgesia were possible.

Long-Term Intrathecal Infusion of Opioid and/or Bupivacaine in the Prophylaxis and Treatment of Phantom Limb Pain.

Introduction and Methods. A prospective, open case study was performed on 37 patients, given intrathecal (IT) bupivacaine alone or bupivacaine/opioid combinations for refractory pain located in the extremities to explore the potential of this therapy for prophylaxis against post-amputation pain (PLP) and/or the treatment of severe, established PLP. Intrathecal infusions were administered before, during, and after amputation, as an attempt to prevent PLP ("prophylaxis group"; n = 21), or to relieve existing severe PLP after previous amputations ("treatment group"; n = 16). Results. All patients but one in the prophylaxis group obtained 60-100% pain relief during intrathecal therapy. Systemic daily doses of opioid decreased approximately threefold from pre-intrathecal therapy, analgesic/sedative consumption was reduced by 50% and nocturnal sleep duration improved from 2-4 h to 6-8 h post intrathecal therapy. During post-amputation IT treatment, transient PLP of less than 1 day duration and/or phantom limb sensation (PLS) occurred in 9 patients in the "prophylaxis group" and in 2 patients in the "treatment group." 4 out of 16 patients (25%) in the prophylactic group and 0 out of 10 (0%) in the treatment group presented neither PLP nor PLS after termination of the IT treatment. Conclusions. Continuous IT infusion of bupivacaine with or without opioid gave satisfactory pain relief during the treatment in 95% of the patients. Continuous IT infusion of bupivacaine, alone or in combination with opioid, relieved severe preexisting PLP during the treatment in 100% of the treated patients, but did not prevent its recurrence after the end of the intrathecal treatment.

Long-Term Intrathecal (IT) Administration of Opioid and Bupivacaine Relieved Intractable Pain in a Patient with Familial Amyloidosis Polyneuropathy: A Case Report(1).

Introduction. At the present time, there is no reliable method or drug for effective relief of the severe pain caused by the amyloldotic polyneuropathy (AP). Objective. To explore the possibility of relieving this type of pain by intrathecal (IT) infusion of opioid (morphine or buprenorphine), with or without bupivacaine. Patients, Materials and Methods. A 49-year-old male AP patient with Intractable pain in the low back, lower abdomen, and lower extremities. Opioids (up to 20 mg parenteral morphine-eq/day), and epidural injections of morphine (up to 36 mg/day) failed to provide long-term satisfactory pain relief. Therefore, an IT catheter was inserted via the L3-L4 interspace with its tip located at the L1-L2 intervertebral disk. Results. Intermittent IT injections of morphine from 5 to 30 mg per day, for 124 days, and continuous IT infusion of morphine (2-4 mg/ml), combined with bupivacaine (1.0-2.0 mg/ml), in daily rates from 2 to 12 ml (median = 9.5) for another 67 days, were associated with occurrence of seizures, suspected to be caused by the IT morphine. Therefore, the IT morphine was replaced with IT buprenorphine. Thereafter, the pain was treated with IT infusion of buprenorphine (0.06 mg/ml) and bupivacaine (1.25 mg/ml) in daily rates from 4 to 13 ml (median = 5) for another 676 days, until the patient's death, for reasons unrelated to the IT treatment. He experienced satisfactory pain relief with daily doses of IT opioid from 4.5 to 39 mg morphine-eq (median = 19.6 mg) and IT bupivacaine from 0 to 20 (median = 12.5). The mean visual Analog Scores (VASmean), decreased from 7 to 0 (out of 10), the gait improved; and nocturnal sleep increased from 1 to 7-8 hours. Respiratory insufficiency (attributed to an an IT daily dose of ∼ 5 mg morphine) and orthostatic hypotension, pareses, and urinary retention occurring at low doses of (12-18 mg/day) of IT bupivacaine were recorded. The patient had the IT treatment for 867 days, of which 777 days (> 90%) were spent at home. Conclusion. Long-term IT administration of opioid and bupivacaine provided satisfactory long-term pain relief in a patient with refractory pain due to AP.

Relaxation of equine tracheal muscle in vitro by different adrenoceptor drugs.

Strips of tracheal smooth muscle from 12 horses were contracted by carbachol in tissue baths under isometric conditions. This contraction (approximately 50% of maximum: EC50) was relaxed completely with adrenoceptor drugs. The only exception was clenbuterol, where the degree of relaxation was approximately 90%. In all horses the EC50-value for isoprenaline (mean 1.6 x 10(-8) M) was less than that for adrenaline (mean 9.6 x 10(-8) M) and noradrenaline (mean 1.8 x 10(-6) M). The potency ratio was 1 < 6 < 110 which indicates that the beta 2-subtype dominates among the beta-adrenoceptors of equine airways. All preparations were also very sensitive to the specific and potent beta 2-receptor agonists clenbuterol (mean 5.7 x 10(-9) M) and procaterol (mean 3.6 x 10(-10) M). No differences in EC50-values due to age, sex and breed were observed in this material. The standard deviation of the mean EC50-values seems to be larger for the specific beta 2-adrenoceptor agonists than for the unspecific. A reason for this could be differences in the pattern of the beta-adrenoceptor population.