Epidural meptazinol for pain relief after lower abdominal surgery

A preliminary investigation is reported into the use of epidural meptazinol for pain relief in 20 patients after major lower abdominal (gynaecological) surgery. Analgesia was rapid in onset (15 minutes), had a median duration of 124 minutes (interquartile range 85-212 minutes) after a single dose of 30 mg and a median duration of 122.5 minutes (interquartile range 70-127 minutes) after a single dose of 60 mg. Overall pain relief, as judged by the patients themselves, was satisfactory in 19 out of the 20 cases. At 30 minutes and 45 minutes pain relief was significantly better with the 60 mg than the 30 mg dose (p less than 0.02). No drug-related adverse effects were observed during the study.     

Pethidine compared with meptazinol during labour

A randomised double-blind comparison of pethidine and meptazinol used as analgesics in labour was carried out in 1,100 consecutive women who would normally have received intramuscular pethidine. Pain assessments at 30-minute intervals were made independently by patients and midwives. Maternal and neonatal side effects were noted. The babies' requirements for resuscitation and weight changes in the first 5 days were studied. There was no difference in the analgesia provided by the two drugs; the pattern of side effects was similar, but the incidence of vomiting was greater following meptazinol administration. The babies in the two groups were similar with respect to resuscitation received, weight gains or losses and the incidence of clinical neonatal jaundice. The most striking findings were the poor quality of pain relief experienced by both groups following parenteral analgesics and the high incidence of side effects.     

Effect of meptazinol on drug absorption and gastric emptying

The rate of paracetamol absorption after oral administration was used as an indirect estimate of the rate of gastric emptying in 24 patients before minor surgery. Patients who received 10 mg morphine or 100 mg meptazinol i.m. had significantly delayed absorption as shown by a lower peak concentration and a delayed time to peak. The mean AUC at 90 min was 1,590, 642 and 159 micrograms min ml-1 after saline, morphine and meptazinol respectively. Meptazinol delayed paracetamol absorption more than morphine.     

Reduction of circulatory reactions to intratracheal intubation--the effect of meptazinol

A controlled, randomized, double blind assessment of the efficacy of meptazinol 3 mg kg-1 in reducing the circulatory responses to tracheal intubation was carried out in 20 ASA class I patients. After thiopentone 4 mg kg-1, meptazinol 3 mg kg-1 (ten patients) or saline (ten patients), and suxamethonium 1.5 mg kg-1 tracheal intubation was carried out, and the changes in pulse rate and arterial blood pressure compared between the groups and with control values. Significance was assessed at the 5% level (Student's t-test and paired t-test). Patients who received saline exhibited a rise in pulse rate, significant 1 and 2 min after intubation, and a significant rise in mean arterial pressure for 5 min after intubation. Patients who received meptazinol exhibited no significant rise in pulse rate, but a significant fall in pulse rate occurred from 5 min onwards. Mean arterial pressure rose significantly for 4 min after intubation but the rise was significantly less than that seen in the saline group. Suppression of spontaneous ventilation or movement in 50% of the group lasted for 7 min and 9 min after induction of anaesthesia in the control group and meptazinol treated group respectively. Meptazinol 3 mg kg-1 modifies the circulatory responses to tracheal intubation, preventing the tachycardia and reducing the hypertension, and causes a short delay in the onset of spontaneous respiration or movement.     

Pharmacokinetics of intravenously administered meptazinol during general anaesthesia in man

The pharmacokinetics of meptazinol (3 mg kg-1 i.v.), a centrally acting opioid agonist-antagonist, were studied in six male and six female patients during anaesthesia with 1-3 vol.% enflurane and an infusion of 10-30 micrograms kg-1 min-1 etomidate. Arterial blood samples were taken up to 300 min postinjection. The plasma meptazinol concentrations, determined by HPLC, best fitted to a three-compartment open mamillary model with central elimination using a non-linear extended least-squares regression analysis. Derived pharmacokinetic parameters indicated a rapid distribution (T1/2 pi = 1.24 +/- 0.83 min, T1/2 alpha = 7.55 +/- 3.97 min), a short elimination half-life (T1/2 beta = 86.9 +/- 15.6 min), a volume of the central compartment twice as large in females (Vc = 0.557 +/- 0.237 l kg-1) as in males (Vc = 0.274 +/- 0.144 l kg-1), a small distribution volume at steady state (Vss = 2.52 +/- 0.66 l kg-1) and a high total plasma clearance (ClP = 1547 +/- 385 ml min-1). The elimination rate microconstant in females (k10 = 0.0577 +/- 0.0337 min-1) was significantly lower than in males (k10 = 0.1093 +/- 0.0437 min-1 with a lower drug fraction in the central compartment in the post-distributive phase (Fc = males: 0.08 +/- 0.02, females 0.19 +/- 0.11). As Vss and ClP were similar in both groups, sex-related differences were only observed in the dynamics of distribution of the drug. From a pharmacokinetic point of view we suspect that meptazinol shows very little cumulation on repeated i.v. administration as necessary during anaesthesia.     

Epidural anesthesia

In epidural anaesthesia, the anaesthetist injects one or more drugs into the epidural space bordering on the spinal dura mater to achieve a "central" and/or "neuraxial" block. It is one of the earliest techniques in anaesthesia, originally performed exclusively with local anaesthetic agents. Adding other drugs and combining epidural with general anaesthesia or adapting the technique to the needs of children has extended the list of indications. Continuous epidural analgesia is an important tool in postoperative pain management. More and more often, the increasing proportion of patients who have comorbidities or are permanently taking medication that modulates the clotting system demands that the anaesthesiologist balance the individual risks and benefits before inducing epidural anaesthesia.     

Epidural abscesses

Until recently epidural abscess was considered a rare, almosttheoretical, complication of central nerve block, but anecdotalreports suggest that this is no longer the case. Thus a reviewof the risk factors, pathogenesis, clinical features and outcomeof this condition is appropriate, the primary aim being to makerecommendations on best anaesthetic practice to minimize therisk of this serious complication. A search of EMBASE©,PUBMED© and MEDLINE© databases from 1966 to September2004 was performed using several strategies, supplemented byreference list screening. Spontaneous epidural abscess is rare,accounting for 0.2–1.2 cases per 10 000 hospital admissionsper year. Estimates of the incidence after central nerve blockvary from 1:1000 to 1:100 000. Risk factors (compromised immunity,spinal column disruption, source of infection) are present inthe majority of patients, whether the condition is spontaneousor associated with central nerve block. Presentation is vague,fever and back pain usually preceding neurological deficit.Diagnosis requires a high index of suspicion and modern imagingtechniques. Treatment involves early surgical drainage to preventpermanent deficit and high dose parenteral antibiotics chosenwith bacteriological advice. Primary prevention depends on properuse of full aseptic precautions. Epidural abscess can be a catastrophicconsequence of central nerve block. Early diagnosis will minimizepermanent damage, but primary prevention should be the aim.There is a need for a large survey to indicate the true incidenceto better inform the risk–benefit ratio for central nerveblock.     

Epidural lipomatosis

ONSET: Epidural lipomatosis is a rare disorder defined as a pathological overgrowth of normal epidural fat. It is more often associated with administration of exogenous steroid with variable duration and doses. Furthermore, it may occur in some patients in the absence of exposure to steroids but generally associated with obesity. Whatever the predisposing factor, the majority of these patients are men. The causal effect of epidural lipomatosis in the development of spinal cord or radicular compression is generally well accepted. DIAGNOSIS: The diagnosis of epidural lipomatosis can be established by melography, computed tomography (CT) and magnetic resonance imaging (MRI). MRI is considered the imaging procedure of choice, allowing an assessment of the extent of lipomatosis and, as well as CT, an identification of the lipomatous tissue. Most cases of epidural lipomatosis with corticosteroid use occur in the thoracic region, while most idiopathic cases occur in the lumbar region. TREATMENT: Management of treatment depends on the severity of the neurological signs and the patient's background. The most common treatment for epidural lipomatosis with corticosteroid use consists in surgical decompression but with a high risk of postoperative mortality. In some cases however, medical treatment includes corticosteroid withdrawal or reduction and calorie restriction, leading to clinical improvement. Treatment for idiopathic epidural lipomatosis is more often medical, based on weight loss and physical therapy with generally successful outcome. The pathogenesis of epidural lipomatosis remains unknown but different suggested hypotheses may lead to a metabolic disorder as the underlying cause.