Adrenaline markedly improves thoracic epidural analgesia produced by a low-dose infusion of bupivacaine, fentanyl and adrenaline after major surgery. A randomised, double-blind, cross-over study with and without adrenaline

BACKGROUND: Basic pharmacological research indicates that there are synergistic antinociceptive effects at the spinal cord level between adrenaline, fentanyl and bupivacaine. Our clinical experience with such a mixture in a thoracic epidural infusion after major surgery confirms this. The objectives of the present study were to evaluate the effects on postoperative pain intensity, pain relief and side effects when removing adrenaline from this triple epidural mixture. METHODS: A prospective, randomised, double-blind, cross-over study was carried out in 24 patients after major thoracic or abdominal surgery. Patients with only mild pain when coughing during a titrated thoracic epidural infusion of about 10 ml.h-1 of bupivacaine 1 mg.ml-1, fentanyl 2 micrograms.ml-1, and adrenaline 2 micrograms.ml-1 were included. On the 1st and 2nd postoperative days each patient was given a double-blind epidural infusion, at the same rate, with or without adrenaline. The effect was observed for 4 h or until pain when coughing became unacceptable in spite of a rescue analgesic procedure. Rescue analgesia consisted of up to two epidural bolus injections per hour and i.v. morphine if necessary. All patients received rectal paracetamol 1 g, every 8 h. Fentanyl serum concentrations were measured with a radioimmunoassay technique at the start and end of each study period. Main outcome measures were extent of sensory blockade and pain intensity at rest and when coughing, evaluated by a visual analogue scale, a verbal categorical rating scale, the Prince Henry Hospital pain score, and an overall quality of pain relief score. RESULTS: The number of hypaesthetic dermatomal segments decreased (P < 0.001) and pain intensity at rest and when coughing increased (P < 0.001) when adrenaline was omitted from the triple epidural mixture. This change started within the first hour after removing adrenaline. After 3 h pain intensity when coughing had increased to unacceptable levels in spite of rescue analgesia (epidural bolus injections and i.v. morphine). Within 15-20 min after restarting the triple epidural mixture with adrenaline, pain intensity was again reduced to mild pain when coughing. Serum concentration of fentanyl doubled from 0.22 to 0.45 ng.ml-1 (P < 0.01), and there was more sedation during the period without adrenaline. CONCLUSIONS: Adrenaline increases sensory block and improves the pain-relieving effect of a mixture of bupivacaine and fentanyl infused epidurally at a thoracic level after major thoracic or abdominal surgery. Serum fentanyl concentrations doubled and sedation increased when adrenaline was removed from the epidural infusion, indicating more rapid vascular absorption and systemic effects of fentanyl.     

Influence of anesthetic technique in postoperative analgesia in thoracic surgery

OBJECTIVE: To compare the intensity of postoperative pain after thoracotomy with 2 anesthetic techniques: 1) thoracic epidural block with bupivacaine administered before surgery (combined anesthesia with isoflurane) and 2) conventional balanced anesthesia with isoflurane and endovenous fentanyl. PATIENTS AND METHODS: Thirty patients scheduled for thoracotomy by lateral incision (T5-T6) were randomly divided into 2 groups of 15. Group A received 8 ml of 0.5% bupivacaine with adrenalin 1:200.000 30 min before start of surgery while group B received 8 ml saline solution through an epidural catheter inserted to T4-T8. Combined anesthesia (4 ml 0.5% bupivacaine through an epidural catheter 150 min after the first dose and isoflurane in 100% oxygen) was used in group A. Group B received balanced anesthesia with endovenous fentanyl 2.5 micrograms/kg and isoflurane in 100% oxygen. The difference in pain intensity during postoperative recovery was assessed by way of the following variables: number of boluses administered by epidural patient-controlled analgesia (bupivacaine 0.0625% and fentanyl 6 micrograms/ml); score on a visual analog scale of 10 at baseline and at 1, 3, 7, 11, 19 and 43 hours after surgery; and need for additional analgesia (diclofenac) during the 43 hours of study. Arterial gases were measured during the preoperative period and at 1, 3, 7, 19 and 43 hours after surgery. RESULTS: No significant differences in pain intensity measured on the visual analog scale, by the number of boluses per patients or by need for additional analgesia were found between the 2 groups. The total number of boluses administered and additional analgesic requirements were greater in the group receiving bupivacaine, although the difference was not significant (p = 0.095 and p = 0.056, respectively). Nor were there significant differences in pH and PaCO2 levels for the 2 groups. CONCLUSIONS: Analgesic efficacy after thoracotomy was similar for our 2 groups receiving either combined anesthesia (epidural bupivacaine at 0.5% and isoflurane) or balanced anesthesia with isoflurane and endovenous fentanyl.     

Effects of continuous epidural administration of fentanyl and morphine on postcesarean pain

We studied the effects of continuous epidural administration of fentanyl and morphine with bupivacaine for management of postcesarean pain. Eighteen patients received either bolus epidural administration of fentanyl 100 micrograms or morphine 3 mg with 0.5% bupivacaine 4 ml, followed by continuous infusion of fentanyl 33 micrograms.ml-1 with 0.17% bupivacaine or morphine 0.21 mg.ml-1 with 0.17% bupivacaine for 48 hours, respectively. Pain score was assessed at 0 h, 12h, 24h and 48h after leaving the operating room. Pain score increased significantly and progressively in the fentanyl group. In all cases pruritus was noted. Severe pruritus was observed in the morphine group significantly more than in the fentanyl group. The current results indicate that morphine may be preferable to fentanyl for postcesarean pain control using the present opioid doses.     

Postoperative patient-controlled epidural analgesia with opioid bupivacaine mixtures

PURPOSE: To determine the efficacy and safety of patient-controlled epidural analgesia of morphine or fentanyl in combination with bupivacaine for postoperative pain relief. METHODS: Forty ASA I-II patients scheduled for major abdominal surgery were studied. After insertion of a lumbar epidural catheter, patients were given a non-opioid general anaesthetic. After surgery patients complaining of pain, received a loading dose of 2 mg morphine (Group I) or 50 micrograms fentanyl (Group II). For continuing pain, 1 mg morphine in 4 ml bupivacaine 0.125% (0.25 mg.ml-1 morphine and 1 mg.ml-1 bupivacaine, Group I) or 20 micrograms fentanyl in 4 ml bupivacaine 0.125% (5 micrograms.ml-1 fentanyl and 1 mg.ml-1 bupivacaine Group II) were administered. Blood pressure, heart rate, respiratory rate and SpO2 were monitored. Assessments of pain (VAS), nausea-vomiting, motor block, pruritus and sedation were recorded for 24 hr. RESULTS: No difference in pain or sedation was observed between groups. The 24 hr postoperative opioid consumption was 15.50 +/- 7.53 mg morphine and 555.10 +/- 183.85 micrograms fentanyl. Total bupivacaine 0.125% consumption was 58.00 +/- 30.14 ml in Group I and 101.05 +/- 36.77 ml in Group II. One patient in Group II complained of motor weakness in one leg. The incidence of nausea (Group I 45%, Group II 10% P < 0.05) and pruritus (Group I 30%, Group II 5% P < 0.05) was less in patients receiving fentanyl. CONCLUSION: Both methods were effective in the prevention of pain but, because of fewer side effects, fentanyl may be preferable to morphine.     

Epidural fentanyl produces labor analgesia by a spinal mechanism

BACKGROUND: The purpose of this study was to determine if epidural fentanyl produces analgesia in laboring patients by a primary spinal or supraspinal action. METHODS: Fifty-four parturients were randomized to receive epidural 0.125% bupivacaine plus one of three treatments: epidural saline-intravenous saline, epidural fentanyl (20 microg/h)-intravenous saline, or epidural saline-intravenous fentanyl (20 microg/h). The study treatments were administered by continuous infusion, whereas epidural bupivacaine use was patient controlled. RESULTS: Epidural bupivacaine use was significantly reduced by epidural (11.5+/-4.6 ml/h) but not by intravenous fentanyl (15.9+/-4.5 ml/h) compared with saline control (16+/-5.9 ml/ h). Analgesia characteristics and side effects were similar among groups. CONCLUSIONS: Low-dose epidural infusions of fentanyl produce labor analgesia by a primary spinal action.     

The influence of epidural administration of fentanyl infusion on gastric emptying in labour

The effect of epidural infusions containing fentanyl on maternal gastric emptying in labour was examined using the rate of paracetamol absorption. Women were randomly allocated to receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine 0.0625% with fentanyl 2.5 micrograms.ml-1 at a rate of 10-12 ml.h-1. Paracetamol 1.5 g was given orally to women after either 30 ml of the infusion solution had been given (mean time 2.5 h, study A) or 40-50 ml (mean time 4.5 h. study B). Six venous blood samples were taken over the next 90 min for measurement of plasma paracetamol concentration. There were no significant differences in maximum plasma paracetamol concentration, time to maximum paracetamol concentration and area under the concentration-time curve between the two groups for study A. In study B the time to maximum plasma paracetamol concentration was significantly delayed in women receiving > 100 micrograms fentanyl compared with controls (p < 0.05). We conclude that the dose of fentanyl that may delay gastric emptying when given by epidural infusion is greater than 100 micrograms.     

Epidural anesthesia for labor in an ambulatory patient

The effectiveness of two epidural analgesic regimens on the ability to ambulate was compared in women in labor by a prospective, randomized, double-blind design. One group of patients received epidural fentanyl, a 75-micrograms bolus and an infusion of fentanyl 2.5 micrograms/mL at 15 mL/h (FENT, n = 53). A second group received ultra low-dose bupivacaine (0.04%), epinephrine (1.7 micrograms/mL), and fentanyl (1.7 micrograms/mL) (BEF, n = 77), a 15-mL bolus followed by an infusion at 15 mL/h. Adequate analgesia was rapidly obtained in 90.6% of patients in the FENT group and 92.2% of patients in the BEF group (P = 0.89). Seventy percent of patients in the FENT group ambulated versus 68% in the other group. The BEF mixture provided analgesia of longer duration (287 +/- 171 min versus 156 +/- 72 min, P = 0.0001). The number of patients delivering during administration of only their study drug (without needing higher doses of local anesthetics) was 52% for BEF and 21% for FENT (P = 0.0005). Hip flexion weakness precluding ambulation occurred in 17% (P = 0.002) of BEF patients and orthostatic hypotension in 9% (P = 0.08). Neither problem occurred in FENT patients. Neonatal outcome was similar in both groups. Approximately 70% of women receiving epidural analgesia with fentanyl or ultra low-dose bupivacaine, epinephrine, and fentanyl may ambulate safely during labor.     

Comparative study of postoperative analgesia with methadone and fentanyl in continuous peridural perfusion

OBJECTIVE: To determine whether continuous epidural perfusion of fentanyl, which is more liposoluble than methadone, provides a similar level of analgesia with fewer side effects than methadone administered by the same route for postoperative pain. PATIENTS AND METHODS: Prospective double blind study of 40 patients, randomly assigned to two groups. Group F (n = 20) received 300 micrograms-1200 micrograms/24 h in epidural perfusion. Group M (n = 20) received 9 mg-18 mg/24 h in epidural perfusion. In both cases treatment was for pain in the first 72 h after abdominal surgery. Analgesia quality was evaluated on a visual analog (VAS) scale from 1 to 10 at rest and moving. Need for complementary analgesia was also recorded, as were side effects related to the technique. RESULTS: Quality of analgesia was good and similar which both drugs. Postoperative pain did not surpass 3 on the VAS at rest or 4.5 while moving, although group F patients' need for complementary analgesia was significantly greater (p < 0.05). The incidence of hypoxemia was greater in group M than in group F (p = 0.05). CONCLUSIONS: Continuous epidural perfusion of fentanyl provides good analgesia and is associated with less hypoxemia than is methadone.     

The effect of supervision of residents on quality of care in five university-affiliated emergency departments

BACKGROUND: The purpose of the study was to compare the analgesic and side effects of two epidurally administered mixtures of bupivacaine and fentanyl with the same drug ratios. METHODS: One hundred patients scheduled for colorectal surgery were randomized to receive a thoracic epidural infusion of either bupivacaine 0.12% with fentanyl 2 micrograms/ml or bupivacaine 0.24% with fentanyl 4 micrograms/ml during 48 h postoperatively. The pumps were adjusted to keep the visual analogue scale (VAS) pain score at 3 or less (on a scale of 0-10) with a minimum of adverse effects. RESULTS: There were no statistically significantly differences between the two groups in VAS pain scores. The average VAS pain score resting varied between 0.5 and 1, and coughing between 1.9 and 3.4. One case of respiratory depression with breathing frequency 7 occurred in each group, but none of the patients required naloxone. One patient in the low concentration group developed partial motor weakness in both legs 36 h postoperatively. Equal drug amounts--bupivacaine 10.8-11 mg/h and fentanyl 18-18.4 micrograms/h--were given in both groups throughout the study. CONCLUSIONS: Both groups had low pain scores with few and comparable adverse effects. It thus seems that the volume is not important when mixtures of bupivacaine and fentanyl in the studies concentrations are infused epidurally at a low thoracic level. Practical reasons favour the higher concentration mixture.     

Treatment of incomplete analgesia after placement of an epidural catheter and administration of local anesthetic for women in labor

BACKGROUND: Approximately 15% of women still have pain after placement of an epidural catheter and administration of local anesthetic for labor analgesia. Two techniques frequently used to treat this pain were compared: (1) withdrawal of the catheter 1 cm and repeated dosing with additional local anesthetic, and (2) repeated dosing with additional local anesthetic without any catheter manipulation. METHODS: Fifteen minutes after placement of a multiple-orifice epidural catheter 5 cm into the epidural space and administration of 13 ml 0.25% bupivacaine to the parturient in labor, the adequacy of analgesia was assessed. All women who had incomplete analgesia were randomized (first intervention) to receive an additional 5 ml 0.25% bupivacaine (local-anestheticonly group) or to receive 5 ml 0.25% bupivacaine after first withdrawing the epidural catheter 1 cm (catheter-manipulation group). If after 15 min the woman still had pain, then (second intervention) the catheter was withdrawn 1 cm and an additional 5 ml 0.25% bupivacaine was administered to the local-anesthetic-only group, whereas 5 ml 0.25% bupivacaine was given to the catheter-manipulation group without further catheter manipulation. The success rate of the second intervention was assessed 15 min later. RESULTS: Seventy-eight women were enrolled in the study, 39 to each group. In the local-anesthetic-only group, 29 (74%) women were successfully treated with the first intervention and the remaining 10 (100%) were successfully treated with the second intervention. In the catheter-manipulation group, 30 (77%) were successfully treated with the first intervention and 7 (100%; 2 patients were not studied because of investigator error) were successfully treated with the second intervention (P=NS). CONCLUSIONS: Administration of additional local anesthetic without first withdrawing the epidural catheter will effectively treat most women for whom analgesia is incomplete after the placement of an epidural catheter during labor.     

Experimental fetal transesophageal and intracardiac echocardiography utilizing intravascular ultrasound technology

The effects of epidural fentanyl on the incidence of maternal hypoxaemia during labour and on neonatal welfare were examined. Women were randomly allocated to receive one of two epidural infusions, bupivacaine 0.125% alone or bupivacaine 0.0625% with 2.5 micrograms.ml-1 fentanyl, and maternal arterial oxygen saturation was monitored continuously until delivery. The median incidence of desaturation (SpO2 < 95%) during the active phase of the second stage of labour was significantly greater in the fentanyl group than in controls (2.9 versus 0.6 min.h-1, p = 0.02). Similarly, the incidence of desaturation to SpO2 < or = 90% was greater in the fentanyl group than in controls (p = 0.02). There was no correlation between maternal oxygenation or plasma fentanyl concentration and neonatal welfare as measured by umbilical arterial and venous blood gas and acid base status, Apgar score and Neurologic and Adaptive Capacity Score.     

Determination of provitamin A of green leafy vegetables by high performance liquid chromatography and open column chromatography

AIM OF STUDY: Intrathecal sufentanil has recently been used in labour as part of a combined spinal epidural technique. This study was conducted to compare its use in combination with bupivacaine for caesarean section with fentanyl added to bupivacaine and bupivacaine alone. METHODS: Sixty ASA I and II patients for non-emergency caesarean section under spinal anaesthesia were divided into three groups to receive 15 micrograms fentanyl added to 7.5 mg bupivacaine, 10 micrograms sufentanil added to 7.5 mg bupivacaine and 7.5 mg bupivacaine. Onset time of sensory blockade, side effects, surgical conditions, neonatal outcome and quality of the anaesthetic was assessed. On the first postoperative day, duration of effective analgesia, side effects and patient satisfaction were noted. RESULTS: The duration of effective analgesia of bupivacaine alone was prolonged with the addition of sufentanil and fentanyl by 358% and 256% respectively. No patient in the sufentanil and fentanyl groups required additional intra-operative analgesics compared with 17.6% of patients in the bupivacaine alone group. There was an increase in incidence of desaturation in the sufentanil group (45%) and fentanyl group (5.6%) compared with the bupivacaine only group (0%). The incidence of pruritus was 35% with sufentanil, 27.8% with fentanyl against 0% with bupivacaine alone. CONCLUSION: The addition of 10 micrograms of sufentanil and 15 micrograms of fentanyl to 7.5 mg of bupivacaine prolonged the duration of effective analgesia and improved intra-operative analgesia. However, the incidence of pruritus and episodes of desaturation were increased more with 10 micrograms sufentanil than with 15 micrograms fentanyl.     

Caudal clonidine and bupivacaine for combined epidural and general anaesthesia in children

BACKGROUND: Clonidine produces analgesia by actions on alpha 2-adrenoceptors and enhances both sensory and motor blockade from epidural injection of local anaesthetics. Low-dose clonidine has been used so far for caudal injection in children. Our aim was to study the perioperative effects of high-dose caudal clonidine when added to low concentration of bupivacaine for combined epidural and general anaesthesia in children. METHODS: After induction of general anaesthesia caudal block was performed either with 1 ml.kg-1 bupivacaine 0.175% with the addition of clonidine 5 micrograms.kg-1 (n = 20), or with 1 ml.kg-1 bupivacaine 0.175% (n = 20). The intraoperative anaesthetic requirements, the perioperative haemodynamic effects, respiratory rate, sedation score, postoperative pain scores and side effects were assessed by a blinded observer. A patient-controlled analgesia system was used for postoperative pain relief. The quality of postoperative pain relief was assessed using Smiley's pain analogue scale. RESULTS: Intraoperative haemodynamic responses did not differ between the groups. However, during emergence from general anaesthesia children in the clonidine group had significantly lower heart rates and blood pressure compared to children in the control group. In addition, heart rates and blood pressures were also lower in the clonidine group in the early postoperative period (P < 0.05). Postoperative analgesia was significantly better in the clonidine group as evidenced by the total number of requests (3 vs 12, P < 0.05) and the total amount of tramadol (20.5 mg vs 72.8 mg, P < 0.05) administered. The duration of the caudal analgesia was significantly longer in the clonidine group (20.9 +/- 7.4 h vs 14.4 +/- 10.9 h, P < 0.05). CONCLUSION: Our results suggest that caudal clonidine 5 micrograms.kg-1 enhances and prolongs caudal blockade with bupivacaine (1.175% in children. It also blocks sympathoadrenergic responses during emergence from anaesthesia. Sedation and cardiovascular effects are observed up to 3 h into the postoperative period.     

Drug-induced gingival hyperplasia and its management--a literature review

The purpose of our study was to find out whether patient-controlled epidural administration (PCEA) of a mixture containing a low-dose local anaesthetic, opioid and alpha 2-agonist provides as good or better postoperative analgesia as continuous epidural administration of the same analgetic solution. METHODS: 30 patients (ASA I-III), scheduled for major abdominal surgery, were randomly divided into 2 groups. 90 minutes after induction of general anaesthesia all patients received a continuous epidural infusion of 5 ml/h of the analgetic solution (50 micrograms sufentanil + 150 micrograms clonidine in 50 ml 0.125% bupivacaine) until the end of surgery. Immediately postoperatively the patients of group A received a continuous infusion of the study solution (5-8 ml/h), the patients of group B received a baseline continuous epidural infusion (3 ml/h), additionally they could self-administer 5 ml boli via a PCEA device. Measurements included the total dose of infused drug solution, pain at rest and on exercise by a visual analogue scale, cardiorespiratory data and side effects within the first 24 hours postoperatively. A standardised interview on analgesia and side effects was held 2 days after surgery. RESULTS: The PCEA group demanded less epidural analgesics (gr. B: 112 +/- 33 ml vs. gr. A: 135 +/- 20 ml) p < 0.01). Both continuous epidural infusion and patient-controlled administration provided very good analgesia at rest (gr. A: VAS 0.4 +/- 0.4 and gr. B: VAS 0.4 +/- 0.5) (n.s.). On exercise continuous epidural infusion of analgesics resulted in significantly lower pain scores (gr. A: 1.9 +/- 1.1) than patient-controlled application (gr. B: 3.4 +/- 1.1) (p < 0.01). We did not notice severe side effects such as respiratory depression or drop of heart rate or blood pressure. CONCLUSION: In patients at rest both continuous and patient-controlled epidural administration of analgesics provides excellent analgesia after major abdominal surgery. Contrariwise, patients on exercise who could use a PCA-device experienced more pain compared to those with a continuous epidural infusion technique. On the other hand the patients of the PCA-group consumed less epidural analgesics. We did not notice any severe side effects such as respiratory depression or cardiovascular instability during the study.     

Risk of myocardial infarction, angina and stroke in users of oral contraceptives: an updated analysis of a cohort study

BACKGROUND: Ropivacaine has shown less systemic toxicity than bupivacaine, and comparatively low muscle-blocking properties could constitute another advantage when used epidurally for obstetric pain relief. We aimed primarily to compare maternal and foetal drug disposition following continuous epidural infusion of ropivacaine or bupivacaine. METHODS: Twenty-four full-term, nulliparous women were randomized to continuous epidural infusion (10 ml/h) of ropivacaine 2.5 mg/ml or bupivacaine 2.5 mg/ml for labour pain relief in a double-blind, parallel-group design. Maternal blood samples were collected up to 24 h after the end of infusion as well as taken from the umbilical cord at the time of delivery. Sensory and motor block as well as analgesia were assessed. All the women were monitored by cardiotocography and neonatal assessment was performed. RESULTS: The sensory block was adequate for both drugs. Higher plasma levels (total and free) were seen with ropivacaine, although the infusion with bupivacaine continued on average for about 2 hours longer. However, the ratios between maternal and umbilical blood concentrations were similar for both drugs. Normal neonatal Apgar and neonatal adaptive capacity scores (NACS) were found in both groups. CONCLUSION: A continuous epidural infusion of 25 mg/h ropivacaine or bupivacaine both produced good labour pain relief. Higher total and free plasma concentrations were seen for ropivacaine. The ratios between maternal and umbilical plasma levels were similar for both drugs.     

Effectiveness, side effects and costs of postoperative pain therapy: intravenous and epidural patient-controlled analgesia (PCA)

PURPOSE: Improvement of the quality of analgesia, reduction of side effects and costs by application of epidural (PCEA) in comparison to intravenous patient-controlled analgesia (PCA) in postoperative pain treatment. METHODS: 62 patients with upper abdominal surgery took part in this randomised prospective study which was approved by the local ethics committee. Epidural catheters were inserted at T 8/9 (group PCEA). General anaesthesia was performed with propofol, sufentanil 2 micrograms/kg, pancuronium, enflurane and O2:N2O = 1:2. Postoperative analgesia consisted of epidural bupivacaine 0.25% + sufentanil 2 micrograms/ml (BS). (bolus 0.05 ml/kg, lockout 10 min) in group PCEA, or of intravenous morphine (bolus 2 mg. lockout 10 min) in group PCA. The following parameters were recorded until the evening of postoperative day 4: pain intensity at rest (VASR, 1-10) and on coughing (VASH, 1-10), blood pressure, heart rate, blood gas analysis, ability to ambulate, pruritus, nausea/vomiting (PONV), patient satisfaction (0-4), time and expenses for postoperative pain treatment. RESULTS: Median VASR (1 vs 2) and VASH (3 vs 4.5) were lower, cough intensity (2 vs 1) and patient satisfaction score (4 vs 3) were higher in PCEA compared to PCA. Ability to ambulate, pruritus, PONV, haemodynamics, paO2 and paCO2 were comparable. Postoperative pain treatment with PCEA was more time-consuming (407 vs 299 min) and expensive (71 vs 40 S/day) than PCA. CONCLUSION: PCEA in comparison to PCA after major abdominal surgery provides superior analgesia with comparable side effects at approximately 80% higher costs.     

Epidural fentanyl, adrenaline and clonidine as adjuvants to local anaesthetics for surgical analgesia: meta-analyses of analgesia and side-effects

BACKGROUND: The risk/benefit ratio of adding fentanyl, adrenaline and clonidine to epidural local anaesthetics for improving intraoperative analgesia is unclear. This meta-analysis was performed to clarify this issue. METHODS: Trials retrieved by search were considered if they were prospective, controlled, epidural analgesia (without combining general anaesthesia) was planned and occurrence of pain during surgery or side-effects were reported. Papers entered meta-analysis if they reached a predefined minimum quality score. Pooled odds ratios (OR) and confidence intervals (CI) were computed. P < 0.05 was considered as significant. RESULTS: Eighteen trials were included in the analysis for fentanyl. Fentanyl decreased the likelihood of pain (OR = 0.21, 95% CI = 0.15-0.30, P < 0.001) and increased the incidence of pruritus (OR = 5.59, 95% CI = 3.12-10.05, P < 0.001) and sedation (OR = 1.88, 95% CI = 1.19-2.98, P = 0.003), compared to control (local anaesthetic without fentanyl). Fentanyl had no effect on respiratory depression, nausea, vomiting and Apgar score. One case of respiratory depression of a newborn was observed. Because of the very low number of trials selected, evaluation of adrenaline and clonidine was not feasible. CONCLUSION: The analysis of current literature shows that the addition of fentanyl to local anaesthetics for intraoperative epidural analgesia is safe and advantageous. The reduction in the incidence of pain during surgery is quantitatively high and therefore clinically significant. Side-effects are mild. Randomized, controlled trials have to be performed in order to clarify the role of adrenaline and clonidine as epidural adjuvants for surgical analgesia.     

Long-term epidural analgesia for pregnancy-induced intercostal neuralgia

Intercostal neuralgia is one of many possible neurological disorders associated with pregnancy. A woman presented in the 34th week of her 4th pregnancy with progressing right-sided pain and hypoesthesia in the ribs, right upper quadrant of the abdomen, and mid-thoracic area of her back. With a clinical diagnosis of pregnancy-related intercostal neuralgia, we inserted an epidural catheter at T8 for ambulatory pain management. A continuous infusion of bupivacaine was titrated by concentration and rate until adequate analgesia was obtained. The final effective dose consisted of 0.125% bupivacaine at 6 ml/h with a patient-controlled bolus dose of 2 ml every 30 min as needed (4-6 boluses per 24-h period). This allowed the patient to continue to work full-time and perform daily activities with minimal discomfort. The epidural infusion was continued until the patient went into spontaneous labor 28 days after the initial clinical visit. A full-term infant was delivered without incident. No major complications occurred such as local anesthetic toxicity, hypotension, motor weakness, or infection. Minor complications included disconnection of the catheter cap and accidental dislodgment, which required placement of a second epidural catheter. For this patient, an appropriately placed chronic epidural catheter and a titrated continuous infusion of bupivacaine provided adequate and safe analgesia for pregnancy-associated intercostal neuralgia.     

Continuous thoracic epidural blockade in combination with general anesthesia with nitrous oxide, oxygen, and sevoflurane in two patients with myasthenia gravis

Continuous thoracic epidural anesthesia (T4/5) using 4-5 ml.h-1 of 1.5% lidocaine with 1:200,000 epinephrine and inhaled anesthesia using nitrous oxide, oxygen and sevoflurane were performed in two patients, (40 and 22 yr-old females) with myasthenia gravis. This combined anesthetic technique provided muscle relaxation for endotracheal intubation and optimal operating conditions, including muscle relaxation and stability of hemodynamics during transsternal thymectomy. Further, continuous epidural anesthesia using 4 ml.h-1 of 0.25% bupivacaine provided postoperative pain relief without other analgesics and stable postoperative respiratory conditions. In conclusion, we confirm the benefits of this technique which provides not only safe and stable conditions during the surgery, but also an improved comfort for patients in the postoperative period following transsternal thymectomy for myasthenia gravis.     

Mucosal melanomas of the head and neck

PURPOSE: To determine the effect of epidural analgesia on biochemical markers of stress, plasma oxytocin concentrations and frequency of uterine contractions during the first stage of labour. METHODS: Nine nulliparous women, in spontaneous labour, with a singleton fetus and cervical dilatation < or = 5 cm were enrolled. Epidural bupivacaine 0.25% (range 10-14 ml) was administered and bilateral sensory blockade to ice (T8-L4) achieved. Blood samples were collected before the epidermal block and every 10 min for one hour after the block was achieved for the measurement of plasma beta-endorphin, cortical, glucose, lactate and oxytocin concentrations. No exogenous oxytocin was given. Intensity of pain was assessed at the time of the blood sampling using a 10 cm visual analogue scale (VAS). The frequency of uterine contractions was recorded for 60 min before and after the epidural block. RESULTS: There was a decrease in plasma beta-endorphin and cortisol concentrations after epidural block (P < 0.01). There were no changes in plasma glucose and lactate concentrations. The mean VAS for pain decreased 10 min after epidural block was achieved and remained < 2 throughout the study period (P < 0.001). Mean plasma oxytocin concentrations did not change. The frequency of uterine contractions before and after the epidural block was similar. CONCLUSIONS: The metabolic stress response to the pain of labour was attenuated by epidural analgesia. In contrast, plasma oxytocin concentration and frequency of uterine contractions were unaffected by the attenuation of metabolic stress response.