Epidural Methadone Research Articles

Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover-design trial.

Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half-life, epidural methadone may provide lasting analgesia with minimal adverse effects; however, human studies are lacking. The aim of the study was to test the hypothesis that epidural methadone would exhibit greater segmental analgesia (analgesia at the dermatome of injection vs. distant dermatomes) than epidural morphine. In a prospective, randomized, double-blinded, crossover study, thirteen healthy volunteers received a 4-mg epidural bolus of methadone or morphine at L3-L4 and underwent repeated assessment of dermatomal heat pain tolerance and pressure pain threshold at lumbar (L3) and trigeminal (V2) dermatomes, pupil diameter, respiratory parameters and venous opioid concentration for 24 h. The primary outcome was selective (lumbar vs. trigeminal) segmental analgesia for heat pain, as a marker of a spinal analgesic mechanism. The degree of segmental analgesia to heat pain tolerance was not different between morphine and methadone (P =.09), although morphine (P =.0009) but not methadone (P =.81) produced significant analgesia to heat pain at the lumbar vs. trigeminal dermatome over 0-12 h. Morphine overall provided longer lasting analgesia to heat pain vs. methadone (24 vs. 2 h, respectively). Morphine elicited greater systemic effects, including miosis (P =.009) and opioid-related adverse effects (P =.002). These results suggest that, with equal epidural doses, both methadone and morphine produced analgesia and methadone did not produce greater segmental effects than morphine. Epidural methadone provided a more favourable adverse effect profile.

Evaluación analgésica de la metadona, en dos dosis asociadas a la lidocaína sin vasoconstrictor, por vía epidural en perros sometidos a castración electiva

Several drugs have used to control pain through various routes, such as epidural. Methadone is a synthetic morphine-like opioid and has used epidurally for pain control, especially during surgical procedures such as orchiectomy. Nine male dogs were selected for epidural methadone analgesic action study in two concentrations, 0.1mg/kg (M01) and 0.3 mg/kg (M03), associated with lidocaine without vasoconstrictor, the control group was appended. epidural lidocaine (LID). To evaluate the groups were measured and statistically analyzed the values of heart rate, respiratory rate, oxygen saturation, temperature and systolic blood pressure. The groups M01 and M03 did not differ statistically, the LID group presented different means of the groups M01 and M03 for the values of heart rate, oxygen saturation and diastolic blood pressure, confirming the need to use analgesic drugs in surgical procedures, especially at times of increased nociceptive stimulation.

Evaluation of methadone concentrations in bitches and in umbilical cords after epidural or systemic administration for caesarean section: A randomized trial

ObjectiveTo measure plasma methadone concentrations in bitches and the umbilical cords of their puppies after systemic or epidural administration. Study designProspective, randomized, clinical study. AnimalsA total of 27 healthy pregnant female dogs undergoing caesarean section, 4.3 ± 2.3 years of age and weighing 19.9 ± 13.2 kg. MethodsThe dogs were randomly divided into three groups: 1) intramuscular methadone (0.3 mg kg–1) (group MET; n = 9); 2) epidural methadone (0.1 mg kg–1) (group METEPI; n = 9); and 3) epidural lidocaine (4.4 mg kg–1) [group CON (control group); n = 9]. Ten minutes before induction, methadone was administered intramuscularly to the group MET dogs. Anaesthesia was induced with propofol and maintained with isoflurane. Cardiovascular and respiratory parameters were monitored throughout the anaesthesia. After induction, epidural anaesthesia was administered to dogs in groups METEPI and CON. Before any treatment (T0) and, as soon as the last foetus was removed from the uterus (T1), venous blood samples were collected from each dog into heparinized tubes; the umbilical cords were collected and stored at –80 °C until pharmacological analysis was carried out. The samples were analysed using ultra performance liquid chromatography. ResultsThe cardiorespiratory parameters of the bitches and of the puppies at birth, and the Apgar scores did not differ significantly between groups. At T1 both the median maternal methadone plasma concentration and the median methadone umbilical cord concentration were higher in group MET compared to group METEPI (p = 0.0018 and p = 0.004, respectively). The maternal plasma concentration was higher than the concentration in the umbilical cords (p = 0.05) in group METEPI but not in group MET (p = 0.25). Conclusions and clinical relevanceEpidural methadone (0.1 mg kg–1) administered to bitches undergoing caesarean section is associated with lower umbilical cord methadone concentrations as compared with intramuscularly administered methadone at higher dosages (0.3 mg kg–1).

Preoperative epidural administration of lidocaine-methadone or lidocaine-fentanyl in female dogs undergoing elective ovariohysterectomy

We compared the analgesia and cardiopulmonary changes induced by epidural methadone or fentanyl in combination with lidocaine in female dogs undergoing elective ovariohysterectomy and anesthetized with propofol. Eighteen female dogs were randomly assigned to two groups and given either methadone (0.3 mg kg?¹) + 2% lidocaine without vasoconstrictor (LM) or fentanyl (5 µg kg?¹) + 2% lidocaine without vasoconstrictor (LF). The drugs were administered epidurally in a volume of 0.25 ml kg?¹. Heart rate (HR), respiratory rate (RR), rectal temperature (RT), systolic blood pressure (SBP), and blood glucose levels were recorded before and 15 minutes after premedication (T0 and T1); 15 minutes after epidural administration (T2); five minutes after dermotomy (T3); five minutes after clamping of the ovarian pedicle (T4); five minutes and 1, 3, 6, 12, 18, and 24 hours (T5, T6, T7, T8, T9, T10, and T11, respectively) after surgery. The number of additional propofol injections and total propofol dose (mg kg?¹) were recorded. Analgesia was assessed using a numerical descriptive scale. SBP and HR were similar in both groups, but hypotension was detected in animals from both groups at different times. Respiratory rate decreased significantly at T6 in the LF group and was lower than in the LM group. Hypothermia was observed in animals from both groups, but RT was significantly lower than baseline values only at T4 in the LM group. Blood glucose levels increased significantly only in the LF group at T4, T7, and T8. All animals in the LF group and eight animals in the LM group required additional propofol injections at T4, but no significant differences were detected in the number of propofol injections and total propofol dose between the LF (3 ± 1 injections, 7.5 ± 4.5 mg kg?¹) and LM (2 ± 2 injections, 4.5 ± 3.4 mg kg?¹) groups. The latency period, anesthetic period, and the duration of surgery were similar in both groups. No animals required rescue analgesia. The lidocaine-methadone and lidocaine-fentanyl combinations caused minimal cardiorespiratory changes, but did not abolish pain at the time of handling of the ovarian pedicle.

Cardiopulmonary and sedative effects of intravenous or epidural methadone in conscious dogs.

Cardiopulmonary and sedative effects of intravenous or epidural methadonewere compared. Six beagles were randomly assigned to group MIV (methadone 0.5mg/kg IV + NaCl 0.9% epidurally) or MEP (methadone 0.5mg/kg epidurally + NaCl 0.9% IV). Cardiopulmonary, blood gas and sedation were assessed at time (T) 0, 15, 30, 60, 120, 240 and 480min after drug administration. Compared to T0, heart rate decreased at T15-T120 in MIV (p<.001) and T15-T240 inMEP (p<.05); mean arterial pressure was reduced at T15-T60 in MEP (p<.01); respiratory rate was higher at T15 and T30 in both groups (p<.05); pH was lower at T15-T120 in MIV (p<.01) andT15, T30 and T120 in MEP (p<.05); PaCO2 was higher at T15-T60 in MIV (p<.01) and T15, T30 and T120 in MEP (p<.01); sedation scores were higher at T15 and T30 in MIV and T15-T60 in MEP (p<.05). At T120 and T240, sedation score was higher in group MEP compared with group MIV (p<.01) In conclusion, cardiopulmonary and sedative effects of identical methadone doses are similar when administered IV or epidurally to conscious healthydogs.

Enhanced antinociceptive efficacy of epidural compared with i.v. methadone in a rat model of thermal nociception

BackgroundThe properties of methadone suggest a potential advantage for epidural over i.v. administration for pain relief, but little supportive evidence exists. MethodsTo investigate the pharmacokinetic and the pharmacodynamic properties of epidural and i.v. methadone, four doses of methadone (0.1, 0.25, 0.5, and 0.75 mg kg−1) were investigated by each route in a rat model. The tail-flick and hot water tail immersion test were used for thermal nociception. The magnitude of antinociceptive efficacy was expressed as per cent maximal possible effect (%MPE) of tail withdrawal latency, and the area under the %MPE vs time curve indicated the cumulative antinociceptive effect. A pharmacokinetic model describing the disposition and elimination of methadone was established. ResultsThe pharmacokinetic profiles of methadone were not significantly different after epidural and i.v. administration. A two-compartment model with saturable elimination provided a good fit of the experimental data. At equivalent doses, epidural methadone produced higher cumulative antinociceptive effect in both thermal models. Supraspinal opioid effect, assessed by pinna reflex presence, was significantly lower with epidural methadone at equivalent doses. The duration of antinociceptive effect was longer with epidural administration of 0.5 and 0.75 mg kg−1 doses. ConclusionsEpidural administration of methadone in rats resulted in systemic exposure similar to that after i.v. administration, but improved thermal antinociceptive efficacy, and reduced supraspinal undesired effects. The findings suggest the presence of local effect at the spinal cord level, in addition to the systemic effect produced by epidural methadone.

Epidural methadone results in dose-dependent analgesia in cancer pain, further enhanced by epidural dexamethasone

Background:This study was designed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone.Methods:In all, 72 cancer patients, 32- to 67-year-old were randomized to six groups (n=12) and prospectively studied to examine analgesia and adverse effects for 3 weeks. Patients received single-dose protocol epidural test drugs: Control group (CG) received epidural 40-mg lidocaine diluted to 10-ml volume with saline. Dexamethasone group (DG) 40-mg lidocaine plus 10-mg dexamethasone. The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine; the 5MetG, 5-mg epidural methadone plus 40-mg lidocaine, the 7.5MetG, 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG, 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone.Results:Groups CG, DG and 2.5MetG were similar regarding analgesia and side effects. Patients from 5MetG and 7.5MetG took 3±1 and 5±1 days, respectively, to restart oral morphine. Patients from 7.5MetDG took 14±2 to restart oral morphine (P<0.001). Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation (P<0.005). Fatigue improved for both DG and 7.5MetDG during 2-week evaluation (P<0.005). By the third week of evaluation, all patients were similar.Conclusions:Epidural methadone plus lidocaine resulted in dose-dependent analgesia, further improved by epidural dexamethasone, which also improved fatigue.

Comparison of analgesic efficacy of epidural methadone or ropivacaine/methadone with or without pre-operative oral tepoxalin in dogs undergoing tuberositas tibiae advancement surgery

ObjectiveTo investigate the clinical efficacy of four analgesia protocols in dogs undergoing tibial tuberosity advancement (TTA). Study designProspective, randomized, blinded study. AnimalsThirty-two client owned dogs undergoing TTA-surgery. MethodsDogs (n= 8 per treatment) received an oral placebo (PM and PRM) or tepoxalin (10 mg kg−1) tablet (TM and TRM) once daily for 1 week before surgery. Epidural methadone (0.1 mg kg−1) (PM and TM) or the epidural combination methadone (0.1 mg kg−1)/ropivacaine 0.75% (1.65 mg kg−1) (PRM and TRM) was administered after induction of anaesthesia. Intra-operative fentanyl requirements (2 μg kg−1 IV) and end-tidal isoflurane concentration after 60 minutes of anaesthesia (Fe′ISO60) were recorded. Post-operative analgesia was evaluated hourly from 1 to 8 and at 20 hours post-extubation with a visual analogue scale (VAS) and the University of Melbourne Pain Scale (UMPS). If VAS > 50 and/or UMPS > 10, rescue methadone (0.1 mg kg−1) was administered IV. Analgesic duration (time from epidural until post-operative rescue analgesia) and time to standing were recorded. Normally distributed variables were analysed with an F-test (α = 0.05) or t-test for pairwise inter-treatment comparisons (Bonferonni adjusted α = 0.0083). Non-normally distributed data were analysed with the Kruskall–Wallis test (α = 0.05 or Bonferonni adjusted α = 0.005 for inter-treatment comparison of post-operative pain scores). ResultsMore intra-operative analgesia interventions were required in PM [2 (0–11)] [median (range)] and TM [2 (1–2)] compared to PRM (0) and TRM (0). Fe′ISO60 was significantly lower in (PRM + TRM) compared to (PM + TM). Analgesic duration was shorter in PM (459 ± 276 minutes) (mean ± SD) and TM (318 ± 152 minutes) compared to TRM (853 ± 288 minutes), but not to PRM (554 ± 234 minutes). Times to standing were longer in the ropivacaine treatments compared to TM. Conclusions and clinical relevanceInclusion of epidural ropivacaine resulted in reduction of Fe′ISO60, avoidance of intra-operative fentanyl administration, a longer duration of post-operative analgesia (in TRM) and a delay in time to standing compared to TM.

A review of epidural and intrathecal opioids used in the management of postoperative pain

Opioids are the most potent centrally acting analgesic drugs for the treatment of pain. For the past years, since the discovery of spinal opioid receptors, the use of spinal opioids has been adopted in clinical practice in the hope of producing intense segmental analgesia that was devoid of the dose-limiting side effects associated with systemic opioid administration. Experimental studies have demonstrated that after their perispinal administration, liposolubility is inversely proportional to their spinal selectivity, which is higher for the most water-soluble drug, morphine, than for other more lipophilic drugs, such as fentanyl and sufentanil. Clinical trials have shown that epidural morphine in the form of extended-release liposome injections gives good analgesia for a period of 48 hours, with no need for epidural catheterization. Conversely, fentanyl is the most appropriate opioid in ambulatory surgery and seems to have the strongest effect at the spinal cord administered epidurally as a bolus and supraspinally using continuous epidural infusion. Epidural methadone and hydromorphone are suitable alternatives for analgesia in the postoperative period, given that they have intermediate pharmacokinetic characteristics with respect to the two aforementioned groups of opioids. All opioids administered intrathecally will produce some degree of spinally mediated analgesia. The main differences are related to their duration of action, rate of clearance, and the pathways by which the drugs reach their receptors in the brain. In general, lipophilic opioids produce short-term analgesia (1-4 hours), which is very useful for immediate postoperative pain. However, morphine produces intense analgesia for up to 24 hours with doses as low as 100 μg.

Comparison of the effects of epidural or intravenous methadone on the minimum alveolar concentration of isoflurane in dogs

The effects of epidural and intravenous (IV) methadone (0.5mg/kg) on the minimum alveolar concentration of isoflurane (ISO(MAC)) were compared in dogs. Six dogs (16.5 ± 2.5 kg bodyweight) received three treatments in random order during isoflurane anaesthesia, with a 7 day washout interval between each study. Methadone was injected via a lumbosacral epidural catheter introduced 10 cm cranially into the epidural canal and the electrical stimulation for ISO(MAC) determination was applied either to the thoracic (EP(T) treatment) or to the pelvic limb (EP(P) treatment) during separate study days. In the IV treatment, ISO(MAC) was determined via electrical stimulation of the pelvic limb. Variables were recorded before (baseline), 2.5 and 5h after drug injection. The ISO(MAC) decreased significantly (P<0.05) from baseline at 2.5 and 5h after methadone in all treatments. At 2.5h, the magnitude of ISO(MAC) reduction did not differ between treatments (mean decreases from baseline: 30-33%). The ISO(MAC) reduction lasted longer following epidural methadone in the thoracic limb (decreases from baseline: 30% at 5h in the EP(T) treatment vs. 19% and 16% in the EP(P) and IV treatments, respectively). Although the isoflurane sparing effect provided by epidural methadone was not significantly greater than IV methadone during the initial stage (2.5h), it was more prolonged than the IV route in specific dermatomes (5h in the thoracic limb) with the epidural technique employed. Methadone may therefore provide a greater isoflurane sparing effect when administered epidurally, compared to IV, when noxious stimulation occurs in specific dermatomes.

Cardiovascular effects of epidural administration of methadone, ropivacaine 0.75% and their combination in isoflurane anaesthetized dogs

ObjectiveTo compare the cardiovascular effects of four epidural treatments in isoflurane anaesthetised dogs. Study designProspective, randomized. experimental study. AnimalsSix female, neutered Beagle dogs (13.3 ± 1.0 kg), aged 3.6 ± 0.1 years. MethodsAnaesthesia was induced with propofol (8.3 ± 1.1 mg kg−1) and maintained with isoflurane in a mixture of oxygen and air [inspiratory fraction of oxygen (FiO2) = 40%], using intermittent positive pressure ventilation. Using a cross-over model, NaCl 0.9% (P); methadone 1% 0.1 mg kg−1 (M); ropivacaine 0.75% 1.65 mg kg−1 (R) or methadone 1% 0.1 mg kg−1 + ropivacaine 0.75% 1.65 mg kg−1 (RM) in equal volumes (0.23 mL kg−1) using NaCl 0.9%, was administered epidurally at the level of the lumbosacral space. Treatment P was administered to five dogs only. Cardiovascular and respiratory variables, blood gases, and oesophageal temperature were recorded at T-15 and for 60 minutes after epidural injection (T0). ResultsMean overall heart rate (HR in beats minute−1) was significantly lower after treatment M (119 ± 16) (p = 0.0019), R (110 ± 18) (p < 0.0001) and RM (109 ± 13) (p < 0.0001), compared to treatment P (135 ± 21). Additionally, a significant difference in HR between treatments RM and M was found (p = 0.04). After both ropivacaine treatments, systemic arterial pressures (sAP) were significantly lower compared to other treatments. No significant overall differences between treatments were present for central venous pressure, cardiac output, stroke volume, systemic vascular resistance, oxygen delivery and arterial oxygen content (CaO2). Heart rate and sAP significantly increased after treatment P and M compared to baseline (T-15). With all treatments significant reductions from baseline were observed in oesophageal temperature, packed cell volume and CaO2. A transient unilateral Horner’s syndrome occurred in one dog after treatment R. Conclusions and clinical relevanceClinically important low sAPs were observed after the ropivacaine epidural treatments in isoflurane anaesthetised dogs. Systemic arterial pressures were clinically acceptable when using epidural methadone.

Epidural methadone for acute post-thoracotomy pain: An alternative to a ropivacaine plus fentanyl-based patient-controlled epidural regimen

Summary Accurate management of acute post-thoracotomy pain can be obtained with epidural local anaesthetics with or without opioids. The routine in our centre for many years has been boluses of epidural methadone with satisfactory results and a lack of serious complication. Objectives To compare the analgesic effectiveness of two epidural regimens for acute post-thoracotomy pain management. Methods We enrolled 49 patients undergoing lung resection by thoracotomy in a prospective, non-blinded open study. Study groups: 25 patients received a patient controlled epidural (PCEA) regimen of 0.16% ropivacaine plus 3.5 μg ml −1 fentanyl, and the other 24 patients receiving 4–6 mg of epidural boluses of 0.1% methadone every 8 h. Results Both regimens provided similar pain relief during the first two postoperative days, however, patients receiving methadone needed less rescue analgesia and presented fewer numbers of hypotensive events compared to PCEA patients. Conclusions Epidural boluses of methadone are as a safe and adequate analgesic regiment as a PCEA with ropivacaine plus fentanyl for post-thoracotomy pain management. Additionally, the cost of our current technique is much lower than the ropivacaine infusion.

Palliative treatment of dyspnea with epidural methadone in advanced emphysema: Chest 2005;128:3322–8

La pathologie infectieuse du sinus sphénoïdal est une pathologie rare parmi les atteintes des autres sinus de la face. Les auteurs rapportent neuf cas de sphénoïdites aiguës et chroniques et analysent les aspects cliniques, bactériologiques et thérapeutiques. Neuf patients ont été recensés rétrospectivement dans notre département, pendant une période de 8 ans. Les patients ont tous bénéficié d'un examen clinique, d'une endoscopie nasale et d'une tomodensitométrie qui a confirmé le diagnostic. Les patients ont tous été revus 1 mois après leur prise en charge puis tous les 3 mois pendant 1 an. Les auteurs ont retrouvé six sphénoïdites aiguës et trois chroniques. L'atteinte était plutôt unilatérale et diagnostiquée aux alentours de la quatrième décennie. Il existait une prédominance féminine. La céphalée (d'expression très variable) restait le symptôme le plus constant des infections aiguës et chroniques. La prise en charge a reposé sur l'antibiothérapie, associée à un traitement chirurgical dans trois cas. Staphylococcus aureus (56 %) fut la bactérie le plus fréquemment isolée dans la pathologie aiguë et Prevotella spp. (71 %) dans la pathologie chronique. Un cas de cécité bilatérale est rapporté. Le diagnostic de sphénoïdite est trompeur. Le praticien doit y penser en particulier devant toute céphalée ne faisant pas sa preuve. Le traitement des sphénoïdites repose sur une antibiothérapie, probabiliste dans un premier temps, efficace sur Staphylococcus aureus et les bactéries anaérobies. De redoutables complications peuvent survenir. Le traitement chirurgical est indiqué en cas d'échec du traitement médical, d'apparition de complication neurologique ou ophtalmologique ou en cas d'infection mycotique. Une surveillance clinique régulière doit être organisée.Infectious diseases of the sphenoidal sinus are rare among affections of other face sinuses. Nine cases of acute and chronic sphenoid sinusitis are analyzed in terms of clinical, bacteriological and therapeutic features. Nine cases were retrospectively registered in our department over a period of eight years. All patients had undergone clinical examination, nasal endoscopy, and scanning for diagnostic confirmation; they were all seen again one month later and every three months during one year. The authors found six acute and three chronic sphenoid sinusitis. The affection was almost unilateral and diagnosed around the fourth decade, with a female predominance. The headache, which expression was very variable, was the most constant symptom of acute and chronic pathologies. Complications are possible and we report a bilateral blindness. The patients received an antibiotic-based therapy, associated to a surgical approach in three cases. Staphylococcus aureus (56%) was the most frequently isolated bacteria in acute affections and Prevotella spp (71%) in the chronic ones. Diagnosing sphenoidal sinusitis is difficult; it should always be considered by the physician when the patient reports a headache. Therapeutic management of sphenoid sinusitis remains the antibiotic therapy effective on Staphylococcus aureus and anaeroby bacteria. Surgical treatment is indicated in case of failure of the pharmacological therapy, in case of neurological or ophthalmologic complication and in the event of mycotic infection. A regular clinical surveillance must be organized.

Palliative Treatment of Dyspnea With Epidural Methadone in Advanced Emphysema

This study investigated whether epidural methadone perfusion at the thoracic level can mitigate dyspnea in patients with advanced emphysema. Open-label clinical trial without a control group. University hospital. The inclusion criteria were a diagnosis of emphysema, basal dyspnea index (Mahler scale) < or = 3, FEV(1) < or = 35%, and no indication for pneumoreduction or lung transplantation surgery. An epidural catheter was inserted at the thoracic level connected to a perfusion pump for administering methadone (6 mg/24 h). Assessments were made at baseline, 1 week, and 1 month after catheter insertion. Pulmonary function tests were performed, and determinations were made of arterial blood gas levels, respiratory control data, dyspnea quantification by Mahler transitional dyspnea index (TDI), and the Borg scale change with inspiratory resistive loading, 6-min walk (6MW) distance, and health-related quality of life using the Chronic Respiratory Disease Questionnaire. Of the nine patients studied, infection and catheter migration lead to suspension of treatment before the end of the study in two cases. A significant improvement in dyspnea occurred by 1 week: mean TDI, 3.77 (SD, 1.98) [p < 0.01]. After 1 month of treatment, there were significant improvements in the 6MW distance (mean, 35.33 m; SD, 17.03; p < 0.05), health-related quality of life (mean, 1.63; SD, 0.36; p < 0.05), and dyspnea (mean TDI, 5.33; SD, 2.16; p < 0.05). In addition, after 1 month, Paco(2) fell by 6.67 mm Hg (p < 0.05) and rapid shallow breathing index decreased from 38 to 27 (p < 0.05). These changes occurred without any alteration in the subject's ability to perceive or respond to inspiratory loading. Epidural methadone perfusion at chest level can effectively palliate dyspnea and improve exercise capacity and quality of life in patients with advanced emphysema, without deterioration in respiratory control or lung function. These data suggest that modulation of spinal cord afferent signaling is an appropriate novel target for dyspnea control in chronic respiratory disease.

Efficacy and Safety of Epidural Opioids for Postoperative Analgesia

Epidural narcotic analgesia was assessed in 66 patients after surgery under epidural and light general anesthesia. Changes of forced expiratory volume in 1 s (FEV 1 ) were measured after upper abdominal or thoracic surgery in 41 patients, and comparisons were made with results in an additional 17 upper abdominal surgery patients who received general anesthesia and muscle relaxants followed by intravenous morphine for postoperative pain relief. Methadone, 1.0 mg, hydromorphone, 1.0 mg, or morphine sulfate, 5 mg, was administered epidurally and increments were repeated as necessary until satisfactory analgesia was reported, with the following results (mean ± SD): intravenous morphine: latency 3 to 10 min, duration 3.1 ± 1.6 h; epidural methadone: latency 17.2 ± 4 min, duration 5.6 ± 2.7 h; epidural hydromorphone: latency 22.5 ± 6 min, duration 9.8 ± 5.5 h; epidural morphine: latency 36 ± 6 min, duration 16.4 ± 7 h. Duration of action was slightly longer after lower abdominal surgery. Addition of epinephrine 1/200,000 to the epidural narcotic solutions did not prolong duration. Narcotic requirements for satisfactory analgesia were approximately the same by the intravenous route as by the epidural route and equivalent to 8.5 to 9 mg of morphine. FEV 1 was reduced to 36.8 ± 13.2% of preoperative control values after general anesthesia and muscle relaxants and to 46 ± 12% of control after epidural and general anesthesia. Intravenous morphine improved FEV 1 to 45.3 ± 12% of control, whereas epidural narcotics and local anesthetics produced a greater increase of FEV, in the following amounts: epidural local anesthetic to 68.7 ± 9.1% of control and epidural narcotics to 67.1 ± 14.7% of control. Epidural narcotics did not cause sympathetic depression or bladder dysfunction, and analgesia was segmental. We conclude that epidural narcotics in adequate dosage are an effective means for production of prolonged and segmental postoperative analgesia.

A comparison of the analgesic effects of caudal epidural methadone and lidocaine in the horse

ObjectiveTo evaluate and compare the effects of caudal epidural administration of methadone (METH) and lidocaine (LIDO) on tolerance to thermal stimulation over the dermatomes of the perineal, sacral, lumbar and thoracic regions in the horse. Study designA blinded, randomized, prospective, experimental cross–over study. AnimalsSeven healthy horses, 15.7 ± 4.9 years (mean ± SD) of age, weighing 536 ± 37 kg. MethodsThe horses were randomly assigned to receive two treatments (group M: METH, 0.1 mg kg−1 or group L: LIDO, 0.35 mg kg−1) at intervals of at least 28 days. An 18–gauge 80–mm Tuohy epidural needle was placed in the first intercoccygeal space (Co1–Co2) in awake standing horses restrained in stocks. Analgesia was assessed by use of a probe maintained at a constant 62 °C by circulating hot water. The maximum stimulation time was 30 seconds. Bilateral stimulation was performed at five defined points. Before drug administration, baseline values of response time to thermal stimuli were obtained. Time to response was then measured 15 and 60 minutes after METH or LIDO administration and then hourly until the response returned to baseline at all stimulation points on two further assessments. Development of any ataxia and/or sedation was recorded. Positive pain responses were defined as purposeful avoidance movements of the head, neck, trunk, limbs and tail. Absence of attempts to kick, bite and turning of the head toward the stimulation site were used to indicate analgesia. ResultsCaudal epidural administration of METH and LIDO significantly increased reaction time to thermal stimulation (one–sample t–test; p = 0.05). Analgesia in the perineal region was present 15 minutes after both METH and LIDO administration and progressed from caudal to cranial dermatones with time. The duration of a significant increase in reaction time was 5 hours after METH injection compared to 3 hours following LIDO. All horses defaecated and urinated normally, and no excitement, sedation or ataxia were observed after METH administration. The horses were unable to defaecate normally and were moderately to severely ataxic with hindlimb weakness after LIDO. ConclusionsCaudal epidural administration of methadone has considerable potential in the management of perineal, lumbo–sacral and thoracic pain in horses. Regional differences exist in the onset, duration and intensity of the pain relief. Clinical relevanceEpidural methadone administration provides analgesia with no measured side effects in these healthy adult horses.

Methadone is safe for treating hospitalized patients with severe pain.

Methadone is still regarded as a second line opioid for patients suffering from severe pain, and is rarely used in hospitalized patients. The infrequent use of methadone is probably due to its long plasma half-life that could lead to accumulation and toxicity. In the present study we report that clinically effective analgesic doses of methadone, given either epidurally or orally, can be used safely for prolonged treatment in hospitalized patients. Over a five-year period we administered methadone at Hadassah Hospital in Jerusalem to 3,954 in-patients with severe pain, 12% of whom were younger than 17 yr. Satisfactory pain relief was recorded in more than 85% of the patients. None of the patients treated with oral methadone developed serious side effects. Three patients, treated with epidural methadone (0.09%), developed a clinically significant respiratory depression. In all three cases, epidural pump failure or pump misprogramming resulted in methadone overdose. None of the children or adults treated with methadone developed addiction during hospitalization. Based on its analgesic properties and marked safety profile, we suggest that methadone could be added to the analgesic armamentarium of in-hospital health-care providers. Moreover, methadone could serve as the opioid of first choice in some in-patient populations.

Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section

Analgesia provided by either 5 mg diamorphine, or 5 mg methadone administered by the epidural route during elective caesarean section was compared in 40 women. The median time to further analgesia in the methadone group was 395 min, and 720 min in the diamorphine group, P = 0.0003. Linear analogue scores to assess pain were measured 2-hourly for 12 h, then again at 24 h postoperatively. Pain scores were significantly lower in the diamorphine group at 8 and 10 h. The median cumulative i.m. morphine dose administered during the first 24 h was 20 mg in the methadone group and 0 mg in the diamorphine group (P = 0.0005). Nausea and pruritus were common side effects in both groups. Continuous pulse oximetry data were available for 12 h post-operatively in 15 patients receiving methadone, and in 17 patients receiving diamorphine. One or more episodes of significant desaturation (< 90% for 30 s), occurred in three patients receiving methadone, and in nine patients receiving diamorphine. Desaturation to 90-92% occurred in a further three patients given epidural diamorphine, and in one further patient given epidural methadone.

Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section

Comparison of epidural methadone with epidural diamorphine for analgesia following caesarean section

Continuous Epidural Methadone Treatment for Cancer Pain

Seventy cancer patients suffering from visceral or somatic pain received continuous epidural methadone (EM) analgesia. Initially, 4 mg of 0.1% methadone was given three times daily. If this dose proved ineffective, it was gradually increased to 8 mg four times daily. With this regimen good pain control was obtained in 56 patients (80%). Patients continued the EM therapy for periods up to 140 days, with an average duration of 27 days. Morphine was substituted for methadone in 14 patients (20%). Four of these patients responded well and continued treatment for an average of 18 days. No serious side effects have been observed with EM. With a proper selection of patients and following strict therapy guidelines, epidural methadone is efficacious in treating cancer pain.