Side effects during continuous epidural infusion of morphine and fentanyl

Respiratory effects, nausea, somnolence, and pruritus were compared during a 48-hr period of continuous epidural morphine (n = 34) and fentanyl (n = 32) infusion in 66 patients following elective total replacement of the hip or knee joint. Respiratory effects were assessed by PaCO2. Side effects were assessed by visual analogue scale and considered to be present when the score was above 30. Assessment was made at preoperative visits then 3, 6, 12, 24, 36, and 48 hr after the epidural injection. The bolus dose and subsequent infusion rate were 3,900 +/- 1,300 micrograms and 427 +/- 213 micrograms.hr-1 for morphine, and 85 +/- 46 micrograms and 56 +/- 27 micrograms.hr-1 for fentanyl. Pain relief was similar in both groups. In the morphine group, PaCO2 elevation and nausea occurred over a period of more than 12 hr (P less than 0.05). In the fentanyl group, there was no PaCO2 change, and nausea was confined to the first few hours. Nausea was more severe (P less than 0.01 at six hours and more frequent (24 hr cumulative incidence, 53 vs 28%, P less than 0.05) in the morphine group. Somnolence was prominent within several hours in two-thirds of patients in both groups. Somnolence continued to decline thereafter in the morphine group, but it was demonstrable in approximately half of the patients throughout the second day in the fentanyl group. The incidence was higher in the fentanyl group at the 48th hr (P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory effects of nitrous oxide during continuous infusion of fentanyl or alfentanil

Two groups of eight patients received infusions of either fentanyl at 3 micrograms kg-1 h-1 or alfentanil at 20 micrograms kg-1 h-1 as supplements to 66% N2O in oxygen anaesthesia, during and after body surface surgery. At the end of surgery, the N2O was reduced to 50% and after measurement of ventilatory frequency, minute ventilation, and the ventilatory response to carbon dioxide, N2O was discontinued. The opioid infusions were continued for a further hour and the ventilatory measurements repeated. Both sets of measurements were compared with preoperative values. Minute ventilation (P less than 0.01), frequency (P less than 0.01) and the response to carbon dioxide (P less than 0.01) were reduced during the infusion of fentanyl with N2O; with fentanyl alone, minute ventilation (P less than 0.05) and the response to carbon dioxide (P less than 0.01) were reduced but to a lesser degree. The elimination of nitrous oxide from the inspired gas mixture produced an increase in frequency (P less than 0.05) and increases in the slope (P less than 0.01) and ventilation at 7.3 kPa (P less than 0.025) of the carbon dioxide response curve. Minute ventilation (P less than 0.01) frequency (P less than 0.05) and response to carbon dioxide (P less than 0.01) were all reduced during the infusion of alfentanil with nitrous oxide; with alfentanil alone, minute ventilation (P less than 0.01), tidal volume (P less than 0.05), the slope (P less than 0.025) and the ventilation at 7.3 kPa (P less than 0.01) of the carbon-dioxide response curve were still reduced.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of continuous epidural bupivacaine infusion plus either continuous epidural infusion or patient-controlled epidural injection of fentanyl for postoperative analgesia.

We compared the postoperative epidural analgesia provided by the continuous epidural infusion of bupivacaine supplemented with patient-controlled injection (PCA) of epidural fentanyl with that provided by a continuous infusion of bupivacaine supplemented with a continuous epidural infusion of fentanyl. Our patient population comprised 16 ASA physical status I or II patients undergoing laparotomy with a midline incision under general anesthesia combined with bupivacaine epidural analgesia. Post-operatively, a continuous epidural infusion of bupivacaine (0.1 mg.kg-1.h-1) was combined with epidural fentanyl given by either (a) PCA (15-micrograms bolus with a lockout interval of 12 min, n = 8) or (b) continuous infusion (1 microgram.kg-1.h-1, n = 8). In the case of inadequate pain relief in the latter group, the fentanyl infusion rate was increased by 10 micrograms/h. Analgesia evaluated by a visual analogue pain score and by a verbal pain score was similarly effective in both groups. The sedation score was also similar in both groups. The total dose of epidural fentanyl administered during the first 24 h was significantly lower in the PCA group than in the continuous infusion group (405 +/- 110 micrograms vs 1600 +/- 245 micrograms, P less than 0.001). The dose of fentanyl given during each 4-h interval ranged between 40 and 160 micrograms in the PCA group and 251 and 292 micrograms in the continuous infusion group. Clinically detectable respiratory depression was not observed in either group. In conclusion, epidural administration of 0.1 mg.kg-1.h-1 bupivacaine combined with fentanyl provides effective postoperative analgesia with a total dose of fentanyl required that is lower when fentanyl is administered by epidural PCA rather than by continuous epidural infusion.     

Ventilatory response to carbon dioxide after intramuscular and epidural fentanyl

The authors compared the effects of administration of fentanyl 200 micrograms on the ventilatory response to carbon dioxide in two groups of nine healthy unpremedicated subjects: one group received fentanyl as an intramuscular injection; in the other group, fentanyl was injected into the epidural space. In the intramuscular group, the slope of the ventilatory response to CO2 did not decrease significantly. In the epidural group, the slope of the ventilatory response to CO2 decreased significantly from 2.48 +/- 1.05 to 1.77 +/- 0.7, 1.74 +/- 0.7, and 2.07 +/- 0.74 L X min-1 X mm Hg-1 at 30, 60, and 120 min after injection (chi +/- SD, P less than or equal to 0.05), respectively. At each time of the study, plasma fentanyl levels were significantly lower in the epidural group than in the intramuscular group (P less than or equal to 0.05). These results suggest that epidural fentanyl induces a nonsystemic ventilatory depression that may be due to the rostral spread of the drug.     

Respiratory effects of epidural fentanyl

Respiratory function following single bolus doses as well as continuous infusions of epidural fentanyl were studied in 21 patients. Respiratory rate decreased significantly and end-tidal CO2 showed a non-significant increase following single doses of epidural fentanyl (1.5 micrograms/kg). These changes occurred within minutes of injection, but could not be attributed solely to rapid systemic absorption of fentanyl from the epidural space. Prior administration of parenteral morphine resulted in significantly higher end-tidal CO2 concentrations and lower respiratory rates following epidural fentanyl. Continuous epidural fentanyl infusion (0.5 micrograms/kg/hour) started 60 minutes after the bolus dose had no effect on end-tidal CO2 concentration or respiratory rate for up to 18 hours. Infusions were continued after the study terminated for up to 9 days, during which there was no clinically significant respiratory depression.     

硬膜外腔持续输注丁哌卡因一芬太尼混合液用于术后镇痛的研究

观察３０例胸、腹部术后患者４８小时的镇痛效果。随机分为三组：Ｉ组（对照组）接受全身性阿片类药物上痛； Ⅱ、Ⅲ组（观察组）用微量泵硬膜外腔持续输注 ０．１％丁哌卡因和 ０．０００５％芬太尼混合液每小时２ｍｌ、５ｍｌ上痛。用药后观察镇痛效果和对呼吸及循环系统的影响。结果：Ⅱ、Ⅲ组镇痛效果较Ⅰ组为好，其镇痛效果持续、稳定、用药量少（Ｐ＜０．０１）。注药期间三组未发生呼吸抑制及循环的明显改变。Ⅲ组个别病例出现皮肤瘙痒，停药后自动缓解。     

Ventilatory effects of subarachnoid fentanyl in the elderly

Twenty-eight elderly patients scheduled for urological surgery were randomly assigned to receive, in a double-blind study, subarachnoid hyperbaric bupivacaine 15 mg with 50 micrograms (group A, n = 7), 25 micrograms (group B, n = 7), or 12.5 micrograms (group C, n = 7) of fentanyl or 1 ml of saline (group D, n = 7) in a total volume of 4 ml. The pattern of breathing and the ventilatory response to CO2 were studied before and 90, 150 and 480 min after the subarachnoid injection. In group A, mild pruritus and sedation occurred in five patients, while nausea, vomiting and periodic breathing occurred in two. In group B, mild pruritus and sedation were observed in four patients, while nausea and vomiting occurred in two. No significant differences in minute ventilation, respiratory drive and respiratory timing were observed between the groups. Patients receiving fentanyl 50 micrograms showed a percentual change from baseline values as function of time (slope VE/PE'CO2) significantly below baseline at 90 and 150 min (p less than 0.05). However, the baseline values in this group reverted after 480 min. No side effects were observed in groups C or D. It is concluded that subarachnoid fentanyl 50 micrograms can cause an early respiratory depression and its use as a postoperative analgesic should be avoided in the elderly.     

Ventilatory effects of laparoscopy under epidural anesthesia

This study evaluates the respiratory effects of laparoscopy under epidural anesthesia in seven female patients (ASA physical status I) scheduled for a gamete intrafallopian transfer procedure. Epidural anesthesia was performed with 15-18 mL of 1.5% plain lidocaine using a catheter inserted at the L3-4 level. The upper level of analgesia to pinprick was measured 20 min after lidocaine injection. Ventilatory measurements and arterial blood gas analyses were performed (a) preoperatively, in the horizontal supine position with a T7-9 level of analgesia; (b) in the 20 degrees Trendelenburg position with a T2-5 level of analgesia; (c) during intraabdominal insufflation of CO2 through the laparoscope; and (d) after CO2 exsufflation by manual compression of the abdomen before removal of the laparoscope while in the horizontal position. On-line measurements of VO2, VCO2, VE, VT, F, and PETCO2 were made using a Beckman metabolic cart, while the patients breathed room air through an anesthetic face mask. No significant changes in the ventilatory variables were observed in the Trendelenburg position. In contrast, CO2 insufflation significantly increased VE (from 9.1 +/- 1.0 L/min to 11.8 +/- 2.6 L/min, mean +/- SD), and F (from 16.9 +/- 1.9 breaths/min to 23.1 +/- 3.3 breaths/min, mean +/- SD), whereas VCO2 remained unchanged. PaCO2 remained constant throughout the study. These results suggest that epidural anesthesia may be a safe alternative to general anesthesia for outpatient laparoscopy, as it is not associated with ventilatory depression.     

Comparison of continuous epidural infusion of fentanyl and bupivacaine with intermittent epidural administration of morphine for postoperative pain management in children

Background: The aim of this study was to compare epidural infusion of bupivacaine and fentanyl and intermittent epidural morphine with regard to analgesic effect, and incidence and severity of side effects in children undergoing major abdominal or genito-urological surgery in order to improve the postoperative pain management of children. Methods: A double-blind, block-randomised study design was used. Thirty-one children aged 3 months to 6 years undergoing major abdominal or genito-urological surgery were studied. After induction of anaesthesia a lumbar epidural catheter was placed at L_3–4 or L_4–5. Postoperatively, the children received either 30 μg/kg of morphine every 8 h or a continuous infusion of fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml at a rate of 0.25 ml.kg^-1.h^-1. All children additionally received rectal paracetamol in doses of 50–100 mg.kg^-1. d^-1 on a regular basis, and if necessary supplementary intravenous morphine in doses of 50 μg/kg. Postoperatively, pain, administration of supplemental morphine and side effects were recorded 5 times by one observer during the day of surgery and the first postoperative day. All children had an epidural catheter throughout the study period. Results: Both regimens provided effective analgesia, but significantly better pain relief was obtained in children receiving the fentanyl/bupivacaine regimen. Sedation, pruritus, vomiting, and administration of antiemetics were seen in both treatment groups, and even though both the incidence and severity of side effects tended to be higher in children receiving morphine, no statistically significant difference was found. No episodes of respiratory depression or motor blockade were noticed. Conclusion: Continuous epidural infusion of fentanyl and bupivacaine was found to be superior to intermittent epidural morphine. The initial regimen should be fentanyl 2 μg/ml and bupivacaine 1.0 mg/ml infused at a rate of 0.25 ml. kg^-1. h^-1.     

Comparison of continuous epidural infusion of morphine/bupivacaine with fentanyl/ bupivacaine for postoperative pain relief

The efficacy and safety of postoperative analgesia with continuous epidural infusion of either morphine or fentanyl in combination with bupivacaine were evaluated in 85 patients, ASA physical status I or II, undergoing thoracic and/or upper abdominal surgery. Patients were treated with one of the combinations for 48 h after surgery. The morphine/bupivacaine group (MB; n = 45) received morphine at the rate of 0.2 mg h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h; the fentanyl/bupivacaine group (FB; n = 40) received fentanyl at the rate of 20 μg–h^-1, and bupivacaine at the rate of 10 mg h^-1 for the first 24 h or 5 mg h^-1 for the second 24 h. The degree of pain relief assessed by the visual pain scale and the modified Prince Henry pain scale was satisfactory in most patients in both groups. In group MB 74% and in group FB 76% of patients did not need any supplementary analgesics. No significant differences were observed between the groups in assessment of pain. The incidence of hypotension ( P < 0.05) and pruritus ( P < 0.05) was higher in group MB than in group FB. None of the patients developed respiratory depression in either group.     

第二产程有背景剂量硬膜外分娩镇痛对产程和分娩结局的影响

目的探讨在产妇自控硬膜外分娩镇痛基础上加用背景剂量方案并持续至第二产程结束的镇痛效果及其是否增加围产期风险。方法本研究是一项回顾性队列研究,选择北京大学第一医院2014年3月和2015年3月所有接受硬膜外分娩镇痛的初产妇503例,按照镇痛方案分成两组,有背景剂量组(P组,n=245)和无背景剂量组(C组,n=258)。收集产妇的基线资料,围产期资料和NRS疼痛评分,分析不同镇痛方案对围产期不良事件的影响。结果 P组第二产程NRS疼痛评分[3(3~4)分vs.5(4~5)分]明显低于C组(P0.001)。P组第二产程时间[50(29~82)min vs.38(24~62)min]明显长于C组(P=0.001),产时出血量[200(100~250)ml vs.150(100~200)ml]明显多于C组(P=0.003)。两组的最终分娩方式(P=0.656)和产后出血发生率(9.8%vs.10.9%,P=0.697)差异无统计学意义。结论相比于单纯自控镇痛,加用背景剂量的硬膜外分娩镇痛提供更好镇痛效果的同时不增加围产期风险,可安全应用于临床。     

Autonomic effects of epidural and intravenous fentanyl

BACKGROUND: We tested the hypothesis that there is greater suppression ofautonomic reflexes during general anaesthesia when fentanylis administered epidurally than when it is given intravenously. METHODS: Ten volunteers were anaesthetized with desflurane. Noxious stimuliof variable intensity were then delivered by tetanic electricalstimuli. Heart rate, arterial pressure, and pupillary dilationin response to these stimuli defined nociception. Seven of thesevolunteers participated twice using a crossover design: theyreceived i.v. fentanyl on one study day and epidurally on theother. Autonomic responses to alternative tetanic stimuli atL4 and C5 dermatomes were measured every 5 min for 3 hafter fentanyl administration. RESULTS: After a brief redistribution period, plasma fentanyl concentrationswere virtually identical on both days. After stimulation ofthe L4 dermatome only, block of pupillary reflex dilation wasgreater by 47 (22)% after epidural fentanyl compared with i.v.fentanyl. Time to maximal depression of reflex dilation afterL4 stimulation was 41 (13) min. Arterial pressure and heartrate decreased after fentanyl by either route but there wereno differences observed between L4 and C5 stimulations. CONCLUSION: We conclude that during general anaesthesia, epidural fentanylenhances antinociception by a spinal mechanism which can bedetected by pupillary dilation but not by changes in arterialpressure or heart rate.     

Post operative analgesia with continuous epidural infusion

Forty eight ASA I or II patients of either sex between 20-70 years undergoing major upper abdominal surgery were grouped into sixteen each, on complaint of pain. They received an epidural bolus dose, followed by infusion of the assigned drug at 4ml per hour through BARD PCA I pump. Pain assessment, for the first four hours, was hourly, and subsequently at l0th, 16th, 22nd, 28th, 36th and 40th hour by VAS and VRS. The groups matched for demographic distribution. All groups had lower mean pain scores at first hour by VAS and VRS. In Group II and Group III, the difference was significant (<0.05) at the 2nd (VAS) and 4th (VRS) hours. From 16th (VAS) and 22nd (VRS) hours, the mean pain score was less and significant (<0.05) in Group III. In all groups sedation ranged from 0-1. There was hypotension in Group I (2/16).urinary retention in Group II (8/9 not catheterised); unilateral sensory impairment and motor weakness in Group I (3/16) and Group III (1/16). This study showed that continuous infusion of low dose morphine with bupivacaine provides better quality post operative analgesia with fewer side effects than bupivacaine or morphine alone.