Epidural opioids in children

Experience with spinal opioids in children is limited but is expanding. Anatomy, pharmacology, technique, and results are reviewed. Complications and side effects are described.     

Epidural and intrathecal opioids

Small doses of epidural and intrathecal opioids produce effective and prolonged analgesia postoperatively, although the quality of analgesia does not differ from when conventional routes are used. The different opioids differ only in the speed of onset and duration of action, and in the incidence of side-effects. 'Minor' complications such as nausea, vomiting, pruritis and retention of urine are relatively common. There is a small incidence of respiratory depression which is delayed for several hours after drug administration and which may be prolonged. It is commoner after morphine and after intrathecal administration, and is also associated with advanced age, concomitant use of other central depressant drugs, respiratory disease and large doses. Because of the potentially lethal nature of this complication, it is recommended that the epidural and intrathecal routes of administration are used only when patients can be closely and constantly observed postoperatively.     

Epidural opioids in obstetrics--a review

Epidural opioids have been used in obstetrics since 1980. Various opioids are reviewed in relation to their pharmacology, their efficacy in labour, during caesarean section and for postoperative analgesia, their side-effects and safety. In this patient population it appears safe to administer epidural opioids on the general ward provided that strict monitoring standards are maintained. Practical considerations of nursing management are discussed.     

Epidural opioids and previous caesarean section

In the following case there was delay in diagnosing uterine rupture in a patient with an epidural in situ. The danger of using large doses of local anaesthetics and opioids epidurally in patients who have had previous caesarean sections is discussed.     

Epidural opioids during laminectomy surgery for postoperative pain.

STUDY OBJECTIVE: To determine whether morphine applied directly to the dura during laminectomy surgery provides superior postoperative analgesia during the first 24 hours. DESIGN: Randomized, double-blind study. SETTING: A university-affiliated hospital. PATIENTS: Twenty ASA physical status I and II patients ages 18 to 60 years. INTERVENTIONS: Simultaneous topical dural application and intramuscular (IM) injection of unknown solutions of saline and morphine 3 mg. MEASUREMENTS AND MAIN RESULTS: Postoperative analgesia was assessed using the visual analog scale (VAS), a modified McGill-Melzack pain questionnaire, subjective nursing evaluations, and the amount of supplemental analgesic medication used. Patients were observed for complications and side effects. Compared with the patients who received epidural saline and IM morphine, the patients who received epidural morphine and IM saline had less postoperative pain as determined by VAS scores, nursing evaluations, and amount of supplemental opioid analgesic doses (1.6 +/- 1.2 vs. 4.1 +/- 1.2 analgesic doses per patient; p less than 0.05) required in the first 24 hours. Minor side effects were similar for the two groups. No patient developed respiratory depression. CONCLUSIONS: Morphine 3 mg applied topically to the dura at the end of laminectomy surgery is a simple, safe, and effective way of providing improved postoperative analgesia.     

Epidural,cerebrospinal fluid,and plasma pharmacokinetics of epidural opioids (part 1): differences among opioids

BACKGROUND: The pharmacokinetics of epidurally administered drugs has been the subject of many studies, yet drug concentration in the epidural space has never been measured. This study was undertaken to characterize the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids on the basis of measurement of drug concentration in each of these compartments after epidural administration. METHODS: Morphine plus alfentanil, fentanyl, or sufentanil were administered epidurally in anesthetized pigs. Microdialysis was used to sample the epidural space and the cerebrospinal fluid for measurement of opioid concentration over time. Plasma samples were obtained from the central venous plasma and the epidural venous plasma. These data were used to calculate relevant pharmacokinetic parameters, including mean residence time, elimination half-lives, areas under the concentration versus time curves, clearance, and volume of distribution for each opioid in each compartment. RESULTS: Some of the more important findings were that the cerebrospinal fluid and plasma pharmacokinetics of the opioids did not parallel their epidural pharmacokinetics and that their hydrophobic character governed multiple aspects of their lumbar epidural pharmacokinetics. CONCLUSIONS: The findings indicate that the spinal pharmacokinetics of these drugs are complex and, in some ways, counterintuitive. Also, the bioavailability of opioids in the cerebrospinal fluid and epidural space is determined primarily by their hydrophobicity, with less hydrophobic drugs having greater bioavailability.     

Epidural opioids as anaesthesia for extracorporeal shock wave lithotripsy in two patients with cardiac disease

Two patients with cardiac disease underwent Extracorporeal Shock Wave Lithotripsy (ESWL) in the Dornier HM3 machine. In order to minimize cardiovascular changes, epidural opioids (fentanyl 100 micrograms in 10 ml saline was used in one patient and meperidine 50 mg in 10 ml saline in the other patient) were used as an alternative to either general anaesthesia or epidural local anaesthesia. Both patients displayed haemodynamic stability, remained pain-free and experienced no complications. Epidural opioids proved a suitable form of anaesthesia for ESWL in these patients.     

Epidural,cerebrospinal fluid,and plasma pharmacokinetics of epidural opioids (part 2): effect of epinephrine

BACKGROUND: The ability of epinephrine to improve the efficacy of epidurally administered drugs is assumed to result from local vasoconstriction and a consequent decrease in drug clearance. However, because drug concentration in the epidural space has never been measured, our understanding of the effect of epinephrine on epidural pharmacokinetics is incomplete. This study was designed to characterize the effect of epinephrine on the epidural, cerebrospinal fluid, and plasma pharmacokinetics of epidurally administered opioids. METHODS: Morphine plus alfentanil, fentanyl, or sufentanil was administered epidurally with and without epinephrine (1:200,000) to pigs. Opioid concentration was subsequently measured in the epidural space, central venous plasma, and epidural venous plasma, and these data were used to calculate relevant pharmacokinetic parameters. RESULTS: The pharmacokinetic effects of epinephrine varied by opioid and by sampling site. For example, in the lumbar epidural space, epinephrine increased the mean residence time of morphine but decreased that of fentanyl and sufentanil. Epinephrine had no effect on the terminal elimination half-life of morphine in the epidural space, but it decreased that of fentanyl and sufentanil. In contrast, in the lumbar intrathecal space, epinephrine had no effect on the pharmacokinetics of alfentanil, fentanyl, or sufentanil, but it increased the area under the concentration-time curve of morphine and decreased its elimination half-life. CONCLUSIONS: The findings indicate that the effects of epinephrine on the spinal pharmacokinetics of these opioids are complex and often antithetical across compartments and opioids. In addition, the data clearly indicate that the pharmacokinetic effects of epinephrine in spinal "compartments" cannot be predicted from measurements of drug concentration in plasma, as has been assumed for decades.     

A comparison of the effects of patient-controlled analgesia with intravenous opioids versus Epidural analgesia on recovery after surgery for idiopathic scoliosis

STUDY DESIGN: Epidural infusion was compared with standard patient-controlled analgesia (PCA) in 50 patients after surgical correction of adolescent idiopathic scoliosis with respect to certain postoperative parameters. OBJECTIVES: To compare postoperative parameters after posterior spinal instrumentation and fusion (PSIF) and to determine whether epidural infusion prolongs hospital stay or increases the risk of complications. SUMMARY OF BACKGROUND DATA: Patient-controlled analgesia and epidural infusion are both safe and effective in controlling postoperative pain after PSIF. One criticism of epidural infusion has been longer hospital stays. No study was found in the literature in which PCA was compared with epidural infusion. METHODS: The records of 50 consecutive patients who had undergone PSIF were reviewed. The epidural group consisted of 30 patients and the PCA group 20. Age, weight, degree of curve, and levels fused were evenly matched. Postoperative parameters including the day that each patient tolerated a full diet, day of independent ambulation, length of hospital stay, and pain control were compared. RESULTS: Pain control was comparable in each group. The epidural group tolerated a full diet earlier and on average were discharged 0.5 days sooner than the PCA group. Both differences are statistically significant. No significant complications were reported in either group. CONCLUSIONS: Epidural infusion of opioids with bupivacaine is safe and effective for controlling postoperative pain after PSIF without an increased complication rate when compared with PCA. In the current study, patients tolerated a full diet and were discharged from the hospital an average of 0.5 days earlier than PCA-treated patients.     

Epidural and intrathecal opioids for postoperative pain management in Europe — a 17-nation questionnaire study of selected hospitals

Background : A questionnaire study conducted with the help of selected contact persons in 17 countries in Europe attempted to create a picture of the practice of acute pain management with the use of spinal opioid analgesia (SOA). Methods : A questionnaire was mailed to anaesthesiologists in 105 European hospitals. Depending on the population, 5–10 hospitals from each country were selected by a country co-ordinator. Results : A total of 101 (96.2%) completed questionnaires were returned. During 1 year SOA was used in 55117 patients (6.6% of all in-patient surgical procedures); of these, 89.2% received epidural opioids and 10.8% intrathecal opioids (ratio 8 : 1). The most common opioid for SOA was morphine; fentanyl was also used quite frequently; 12 different opioids and 8 non-opioids had been used. ASA 1–2 patients receiving epidural morphine were nursed on surgical wards in 58.4% of the hospitals; in 25.7% of hospitals even ASA 3–4 were nursed on surgical wards. Respiratory depression (requiring naloxone treatment) was noted in 45 of the 49 183 patients who received epidural opioids (0.09%); 33 of these patients had received morphine. In more than 75% of hospitals the monitoring variables were respiratory rate, sedation level and pulse oximetry. There was a great difference between hospitals and countries regarding duration of monitoring. Conclusions : This questionnaire study showed that SOA was used in about 7% of 836 000 in-patients undergoing surgery at the 105 selected hospitals. Epidural opioids were used eight times more often than intrathecal opioids. Morphine was the commonest opioid for SOA. The duration of monitoring differed greatly between hospitals and countries; the need for official guidelines is emphasized.     

Update on opioids

After feverish interest in the 70 s and 80 s, opioid pharmacology has entered a quieter phase. Molecular biologists have confirmed the existence of the opioid receptor family, which includes μ, κ and δ receptors as well as the ORL-1, nociceptin receptor. Knockout studies of these receptors in mice have produced evidence of splice variants which could explain some of the subtypes of these receptors reported in the earlier literature. Endogenous opioid peptides have been isolated which have selectivity for each or these receptors. The most recent are the tetrapeptide endomorphins with selectivity for μ opioid receptors. The μ receptor still accounts for most of the activity of clinically useful opioid drugs, but there have been some interesting developments in our understanding of the role of opioids in peripheral analgesia. Clinical advances revolves around modifying delivery systems, novel uses for existing drugs and combining existing opioid drugs with other compound to reduce side effects.