Mg Of Preservative-free Morphine Research Articles

445 Evaluation of Low Dose Intrathecal Morphine Delivery in the Treatment of Chronic Pain

INTRODUCTION: The use of low-dose intrathecal morphine via a morphine drug delivery system is an alternative to oral analgesics in the treatment of chronic pain. METHODS: This was a retrospective chart-review. Patients were enrolled from June 2016 to April 2019. An out-patient intrathecal morphine trial was performed by injecting a single dose of 0.1-0.2 mg of preservative-free morphine in the lumbar intrathecal space. Following at least 60% reduction in pain, patients were weaned off oral analgesics completely over several weeks, and a permanent intrathecal catheter and morphine pump was implanted. Follow-up data was included at 3 and 6 months and 1 and 3 years. RESULTS: 20 patients were enrolled (median age 59, 60% female). 10 patients were diagnosed with CPS and 10 were diagnosed with PLS. Pain was significantly controlled and reduced at each time point post-implantation compared to baseline. (p < 0.05). Intrathecal dosing did increase over the 3-year period on average, but the increase in dose was moderate. (p < 0.01) (median increase: 0.09 mg/day over 3 years).All patients were on oral medication for their pain prior to implantation as summarized: Remarkably, no patients previously taking oral opiates/analgesics restarted oral opiate/analgesic therapy following implantation up to and including the 3 years follow-up. There were no infections or complications present in the study. CONCLUSIONS: Low dose intrathecal drug delivery was shown to significantly reduce pain following treatment at each follow-up time point. This study further characterizes the efficacy of the use of low-dose intrathecal drug delivery in the treatment of chronic pain. A future multi-center study is desired.

363 Efficacy of Flexible Intrathecal Morphine Delivery in the Treatment of Chronic Pain

INTRODUCTION: The use of intrathecal morphine via a morphine drug delivery system has been shown as a promising alternative to the treatment of chronic pain. These programmable devices can deliver morphine via simple or flexible programs. Simple programs release morphine continuously at the same rate over a 24-hour period, whereas flexible programs are optimized to release different dosages at different times. METHODS: Patients were enrolled at St. James Mercy Hospital, University of Rochester, New York from February 2016 to February 2020. An out-patient intrathecal morphine trial was performed by injecting a single dose of 0.1-0.3 mg of preservative free morphine in the lumbar intrathecal space. Following at least 60% reduction in pain compared to baseline, a permanent intrathecal catheter and morphine pump were implanted. The drug delivery system was programmed to deliver morphine doses in a simple continuous or flexible mode. Follow up visits occurred between 12 and 60 months, and the efficacy of the flexible dosing was assessed. RESULTS: 58 patients enrolled (34 female, 24 male, median age 59), 46 patients were on flexible dose morphine and 12 were on simple dose morphine. Statistical analysis found a significant difference in pain reduction between the two groups (p < 0.01). The flexible sample had a mean reduction in pain of 8.72 and the simple sample had a mean reduction in pain of 8.17 out of 10 points on the 0-10 pain scale. There were no infections or complications present in the study. CONCLUSION: While both flexible and simple program intrathecal morphine drug delivery system proved effective in reducing chronic pain, flexible programs were significantly more effective. A future multi-center study with a larger sample size is desired.

Continous Epidural Butorphanol Decreases the Incidence of Intrathecal Morphine-Related Pruritus After Cesarean Section: A Randomized, Double-Blinded, Placebo-Controlled Trial

This randomized, double-blinded, placebo-controlled trial investigated the effect of continuous epidural butorphanol on intrathecal morphine-related pruritus in patients undergoing cesarean section. Eighty-three patients undergoing elective cesarean section under spinal anesthesia (1.5 mL of isobaric bupivacaine 0.5 % and 0.1 mg of preservative-free morphine) were enrolled in this study. Subjects were randomized to receive epidural butorphanol (n = 43) or normal saline combined bupivacaine (n = 40). In the study group, after the umbilical cord was clamped, patients were administered an epidural loading dose of 1 mg followed by a 48-h infusion of 0.004 % butorphanol with 0.1 % bupivacaine at a rate of 2 mL/h. In the normal saline group, saline was used for the loading dose and the infusion 0.1 % bupivacaine at a same rate. Postoperatively, a blinded observer recorded the incidence/severity of pruritus, visual analog pain scores and sedation level at 1, 3, 6, 9, 12, 24 and 48 h. The 48-h consumption of breakthrough analgesic (tramadol) was also noted. The primary outcome was the incidence of pruritus at 48 h. At 48 h, the incidence of pruritus was significantly lower in the butorphanol group (16.3 vs. 52.5 %; P < 0.001). Furthermore, compared with the normal saline group, the intensity of pruritus was also decreased with epidural butorphanol at 3, 6 and 9 h (all P ≤ 0.008). The pain scores were significantly lower at 12, 24 and 48 h (all P < 0.05) in the butorphanol groups. Patients only receiving bupivacaine required a higher cumulative dose of tramadol (37.5 ± 62.8 vs. 9.3 ± 36.6; P = 0.014). In patients undergoing elective cesarean section, continuous epidural butorphanol with bupivacaine decreases the incidence and severity of intrathecal morphine-related pruritus without adversely affecting the quality of postoperative analgesia.

Intra-articular clonidine vs. morphine for post-operative analgesia following arthroscopic knee surgery (a comparative evaluation)

In a prospective, double-blind, randomised study, 30 ASA I patients were allocated to three groups in an attempt to find out the best post-operative analgesic following arthroscopic knee surgery under epidural anaesthesia. Group I patients received 5 mg of preservative-free morphine in 20 ml of normal saline, group II patients received 150 μg of clonidine in 20 ml of normal saline and group III patients received 20 ml of normal saline only. The post-operative pain was evaluated by a visual analogue scale and the need for rescue analgesic was assessed post-operatively for 12 h. We conclude that intra-articular administration of 150 μg of clonidine gives a longer lasting pain relief post-operatively (4–12 h) as compared to 5 mg of preservative-free morphine (3 h). No side effects were noted with either of the drugs.

EFFECT OF POSITION ON DURATION OF SPINAL BLOCKADE IN OBSTETRICAL PATIENTS

S377 INTRO: Several studies and texts [1,2,3,4,5] have suggested that hyperbaric spinals placed with patients in the left lateral decubitus position give inadequate blockade for cesarean section. This recommendation is in contrast to the standard clinical practice at several institutions. We, therefore, conducted the following study to determine if patient position during the placement of spinal blockade affected adequacy or duration of anesthesia. METHODS: After an investigational review board approval, and obtaining informed consent, 33 women presenting for elective cesarean section within 3 weeks of term were randomized to one of two groups, either left or right lateral decubitus position for placement of the spinal anesthetic. Fetal heart rate was monitored using the doppler technique throughout spinal placement. A 25 gauge Whiticare spinal needle was placed at the L3-4 or L4-5 interspace. 1.6 ml of 0.75% bupivacaine mixed with 8.25% dextrose and 0.3 mg of preservative free morphine was injected into the intrathecal space after needle placement was confirmed by free flow of CSF. Immediately after withdrawing the spinal needle, the patient was turned supine and left uterine displacement was achieved using a right hip wedge. Spinal sensory levels were assessed at 2, 5, 10 and 90 minutes bilaterally following spinal placement using loss of sensation to pin prick by a blinded observer. Maximal blood pressure drop, ephedrine dose, 1 and 5 minute Apgar scores, fetal cord pH, and surgical duration were recorded for each patient. The results were analyzed using two sample t-test. P=0.05 was considered significant. A power analysis was conducted for sample size determination. RESULTS: 18 patients were randomized to the left lateral decubitus position while 15 were randomized to the right lateral decubitus position. There was no statistically significant difference between groups in any measured variable (see Table 1). pH values were obtained for 8 patients in each group.Table 1In no patient was the anesthetic considered inadequate or was postural manipulation required to facilitate cephalad spread the local anesthetic. CONCLUSIONS: Despite previous reports in the literature to the contrary, we found that patient position during placement of hyperbaric spinal blockade had no statistically significant effect on the duration or effectiveness of spinal anesthesia. In addition, there were no adverse effects on the fetus as measured by fetal heart rate tracings during spinal placement, cord pH or Apgar scores.

Ephedrine-Induced Coronary Artery Vasospasm in a Patient with Prior Cocaine Use

Ephedrine-Induced Coronary Artery Vasospasm in a Patient with Prior Cocaine Use

Comparison of metoclopramide and ondansetron for the prevention of nausea and vomiting after intrathecal morphine

Nausea and vomiting remain unpleasant side effects of intrathecal (i.t.) morphine and of the numerous therapies tried, only prophylactic intravenous (i.v.) metoclopramide has been reported to be promising. Seventy-three patients, scheduled for orthopaedic prosthesis surgery of the hip or knee were studied. They received 4 mL of plain bupivacaine and 0.3 mg of preservative-free morphine i.t. for anaesthesia. The test drugs given in a double-blind and randomized fashion, were either metoclopramide 20 mg, three times, at 6 h intervals (23 patients), ondansetron, 8 mg, twice, at 12 h intervals (25 patients), or 0.9% saline three times, at 6 h intervals (25 patients). The occurrence of nausea, vomiting and pain was followed for 24 h. The incidences of nausea and vomiting were 60% (15/25) and 56% (14/25) in the saline group, 52% (12/23) and 48% (11/23) in the metoclopramide group, and 52% (13/25) and 40% (10/25) in the ondansetron group. Incidences of severe vomiting were 24, 35 and 12%, respectively. Eight patients in the saline group, seven in the metoclopramide and 10 in the ondansetron group did not need additional opioids for post-operative pain relief. We conclude that, metoclopramide and ondansetron were not better than saline in the prevention of post-operative emesis induced by intrathecal morphine.

Intra-articular morphine versus bupivacaine for postoperative analgesia following knee arthroscopy

In a prospective, double blind, randomized study, 30 ASA I patients were allocated to three groups depending on the drug injected intra-articularly, in an attempt to establish the best postoperative analgesic protocol following knee arthroscopy. Group 1 received 3 mg of preservative-free morphine in 25 ml saline; group 2, 5 mg of preservative-free morphine in 25 ml saline; and group 3, 25 ml 0.25% bupivacaine. The degree of postoperative pain was evaluated by visual analogue scale and the need for additional analgesics at 1, 2, 3, 8 and 24 h. We conclude that bupivacaine 0.25% provides analgesia of early onset and of short duration. While 3 mg-preservative free morphine provides moderate postoperative analgesia with peak effect during the eighth postoperative hour, 5 mg preservative-free morphine provides effective and long lasting (more than 24 h) pain relief. No side effects were noted.

Lumbar Discectomy

A technique for extended ambulatory epidural pain control after lumbar discectomy is described; preliminary results with 45 patients are reported; and alternative methods of narcotic analgesia are reviewed. In this technique, an absorbable gelatin sponge (Gelfoam, Upjohn Co., Kalamazoo, MI) is contoured to the laminotomy defect, placed in methylprednisolone acetate (40-80 mg), and then injected with 2 to 4 mg of preservative-free morphine (a small needle was used to fill the sponge). The sponge is placed over the defect before closure. A review of office and hospital records was conducted. The series consisted of 33 men and 12 women (mean age, 39 yr; range, 24-57 yr); records showed narcotic use in 34 patients (parenteral in 3) and work-related injuries in 14 patients. Thirty-three patients were ambulatory postoperatively on the day of surgery; all were ambulatory by postoperative day (POD) 1. On the day of surgery, 18 patients did not require any postoperative analgesics; on POD 1, 22 patients did not require analgesics. Six patients received parenteral narcotics; four received one dose only, and two had two or more doses. Thirty-one patients were discharged from the hospital on POD 1, and 10 were discharged POD 2. The other patients were discharged from the hospital on POD 3 (three patients) or POD 4 (one patient). When they were discharged, all patients received a limited supply of acetaminophen with codeine for pain control at home. After discharge, phone follow-up (at 1 week) and office follow-ups (at 3-5 weeks) revealed only one patient with more than mild discomfort. Three patients required one-time bladder catheterization, and one patient had presumed discitis 1 month postoperatively. In a control group who had undergone surgery 3 months previously, the average day of discharge had been POD 3.07; no control patient had been discharged on POD 1, and only 20% had been discharged on POD 2. This method provides effective, safe, and extended analgesia after lumbar discectomy.

Preoperative Analgesia with Epidural Morphine

In a prospective double-blind study, we examined the effects of preoperative epidural morphine associated with general anesthesia (GA) on intra- and postoperative analgesic requirements over a 3-day postoperative period. Twenty patients scheduled for major intraabdominal surgery were randomly assigned to two groups: a control group (n = 10) and an epidural group (n = 10) which received an epidural injection of 5 mg of preservative-free morphine in 10 mL of 0.9% saline. Afterward, both groups received the same GA. Postoperative pain relief was achieved with intravenous (IV) boluses of morphine using a patient-controlled analgesia device. We found smaller opioid requirements in the epidural group than in the control group for intraoperative fentanyl (465 +/- 179 micrograms vs 983 +/- 682 micrograms), for postoperative morphine at 12 h (3.1 +/- 3 mg vs 21.4 +/- 13.8 mg) and 24 h (9.1 +/- 6.4 mg vs 20.6 +/- 9.8 mg), and for the cumulated needs over the 3-day postoperative period (37 +/- 24 mg vs 86 +/- 42 mg). The consumption of IV morphine by the control group decreased over time (P < 0.001, r = 0.44), whereas, in the epidural group, consumption remained constant and small during the 3 days. The maximum pain score was significantly lower in the epidural group than in the control group at 24 h (0.65 +/- 2.4 vs 3 +/- 2), at 36 h (0.3 +/- 0.6 vs 3 +/- 2.7), and at 60 h (0.1 +/- 0.3 vs 1.8 +/- 1.2) after surgery. These results suggest that a single epidural injection of 5 mg of morphine before major surgery produces intra- and postoperative pain relief for at least 3 days.

Intrathecal narcotics for obstetric analgesia in a community hospital

OBJECTIVE: Our objective was to establish whether intrathecal narcotics for obstetric analgesia offer an adequate and cost-effective alternative to epidural analgesia with minimal side effects in our small, semirural community hospital with limited anesthesia coverage. STUDY DESIGN: Low-risk patients at ≥35 gestational weeks in active labor were offered intrathecal narcotics. A retroactive chart review of every patient receiving an intrathecal injection was compared with a chart review of the next consecutive low-risk patient who did not receive an intrathecal narcotic. Age, parity, and status of labor at the time of application were noted, as was the subsequent rate of labor and the type of delivery. Side effects such as changes in vital signs, headache, vomiting, pruritis, urinary retention, and/or respiratory depression were noted. All study patients received fentanyl, 25 to 35 μg, plus 0.25 to 0.3 mg of preservative-free morphine combined with 6 to 8 mg of lidocaine. Within 15 minutes of delivery intravenous nalbuphine (Nubain), 5 mg, and oral naltrexone, 12.5 mg, were administered. Pain relief was recorded as excellent, satisfactory, or unsatisfactory (requiring additional medication). RESULTS: During the 30-month review period, 90 patients (3% of total deliveries) received intrathecal narcotics. There were three sets of twins, for a total of 93 live births. Ten patients (11%) required primary cesarean section, and of the 83 vaginal births 35 (38%) were spontaneous, two (2%) required forceps deliveries, and 46 (49%) were delivered by vacuum extraction, which was significantly higher than the 28 (31%) for controls. The rate of labor was not affected, with both groups requiring a similar rate of oxytocin (Pitocin) augmentation. Significantly more patients receiving intrathecal narcotics experienced pruritus and urinary retention compared with controls. There was no incidence of respiratory depression. Eighty-four (93%) of the 90 patients reported excellent pain relief, five patients had satisfactory relief lasting 2.5 to 6 hours, and one was unsatisfactory. CONCLUSIONS: In our hospital with limited anesthesia services intrathecal narcotics offer excellent labor pain relief with manageable side effects and without adverse obstetric outcome. (AM J Obstet Gynecol 1994;170:1643-8.)

Intrathecal narcotics for obstetric analgesia in a community hospital

Our objective was to establish whether intrathecal narcotics for obstetric analgesia offer an adequate and cost-effective alternative to epidural analgesia with minimal side effects in our small, semirural community hospital with limited anesthesia coverage. Low-risk patients at > or = 35 gestational weeks in active labor were offered intrathecal narcotics. A retroactive chart review of every patient receiving an intrathecal injection was compared with a chart review of the next consecutive low-risk patient who did not receive an intrathecal narcotic. Age, parity, and status of labor at the time of application were noted, as was the subsequent rate of labor and the type of delivery. Side effects such as changes in vital signs, headache, vomiting, pruritus, urinary retention, and/or respiratory depression were noted. All study patients received fentanyl, 25 to 35 micrograms, plus 0.25 to 0.3 mg of preservative-free morphine combined with 6 to 8 mg of lidocaine. Within 15 minutes of delivery intravenous nalbuphine (Nubain), 5 mg, and oral naltrexone, 12.5 mg, were administered. Pain relief was recorded as excellent, satisfactory, or unsatisfactory (requiring additional medication). During the 30-month review period, 90 patients (3% of total deliveries) received intrathecal narcotics. There were three sets of twins, for a total of 93 live births. Ten patients (11%) required primary cesarean section, and of the 83 vaginal births 35 (38%) were spontaneous, two (2%) required forceps deliveries, and 46 (49%) were delivered by vacuum extraction, which was significantly higher than the 28 (31%) for controls. The rate of labor was not affected, with both groups requiring a similar rate of oxytocin (Pitocin) augmentation. Significantly more patients receiving intrathecal narcotics experienced pruritus and urinary retention compared with controls. There was no incidence of respiratory depression. Eighty-four (93%) of the 90 patients reported excellent pain relief, five patients had satisfactory relief lasting 2.5 to 6 hours, and one was unsatisfactory. In our hospital with limited anesthesia services intrathecal narcotics offer excellent labor pain relief with manageable side effects and without adverse obstetric outcome.

Evaluation of the Effect of Perineuronal Morphine on the Quality of Postoperative Analgesia After Axillary Plexus Block

A randomized, double-blind study was performed on 50 patients scheduled for elective hand and forearm surgery under axillary plexus block to evaluate the effect of perineuronal morphine on the quality of postoperative analgesia. Patients were divided into two groups. In group A (n = 25) 5 mg of preservative-free morphine in 1.0 mL of 0.9% saline was added to the local anesthetic solution (20 mL of 1% plain lignocaine, 20 mL of 0.5% plain bupivacaine). They also received an intramuscular placebo injection of 1.0 mL of 0.9% saline in the upper thigh. In group B (n = 25), 1.0 mL of 0.9% saline was added to the local anesthetic solution and patients received an intramuscular injection of 5 mg of preservative-free morphine in 1.0 mL of 0.9% saline in the thigh. The addition of morphine to the local anesthetic solution for the axillary block did not shorten the onset time of the block, improve the quality of postoperative pain relief, or provide longer lasting analgesia than that obtained with intramuscular morphine.

Epidural Steroids, Epidural Morphine and Epidural Steroids Combined with Morphine in the Treatment of Post-Laminectomy Syndrome

Epidural morphine injection followed by a steroid has been reported to be effective for the post-laminectomy pain ('failed back') syndrome. This double-blind, parallel study was undertaken to evaluate that mode of therapy. Twenty-two patients who had undergone at least one prior laminectomy, who were still symptomatic, were randomized to receive 50 mg of lidocaine epidurally with: (a) 75 mg triamcinolone diacetate (TR); or (b) 8 mg of preservative-free morphine (MP); or (c) both (TR and MP), at 1 month intervals for 3 consecutive months. The spinal interspace identified with the patients' pain complaint was the site of injection. For each treatment, patients were admitted to the Clinical Research Center for 24 h and their condition continuously monitored with a pulse oximeter and apnea monitor. Five to 7 patients in each group had pain relief for less than 1 month. No patient given morphine had pain relief for more than 1 month. Life-threatening ventilatory depression occurred in the group given triamcinolone and morphine. The use of morphine alone or combined with slow release triamcinolone does not appear to be appropriate for the treatment of the post-laminectomy pain syndrome.

Epidural steroids, epidural morphine and epidural steroids combined with morphine in the treatment of post-laminectomy syndrome

Epidural morphine injection followed by a steroid has been reported to be effective for the post-laminectomy pain (‘failed back’) syndrome. This double-blind, parallel study was undertaken to evaluate that mode of therapy. Twenty-two patients who had undergone at least one prior laminectomy, who were still symptomatic, were randomized to receive 50 mg of lidocaine epidurally with: 1. (a) 75 mg triamcinolone diacetate (TR); or 2. (b) 8 mg of preservative-free morphine (MP); or 3. (c) both (TR and MP), at 1 month intervals for 3 consecutive months. The spinal interspace identified with the patients' pain complaint was the site of injection. For each treatment, patients were admitted to the Clinical Research Center for 24 h and their condition continuously monitored with a pulse oximeter and apnea monitor. Five to 7 patients in each group had pain relief for less than 1 month. No patient given morphine had pain relief for more than 1 month. Life-threatening ventilatory depression occurred in the group given triamcinolone and morphine. The use of morphine alone or combined with slow release triamcinolone does not appear to be appropriate for the treatment of the post-laminectomy pain syndrome.

Mini-Dose Intrathecal Morphine for the Relief of Post-Cesarean Section Pain

Thirty-three healthy women at term were scheduled to receive spinal anesthesia with 0.75% bupivacaine in 8.25% dextrose. In a double-blind fashion, all patients also received an intrathecal addendum of 0.5 ml of saline alone or containing either 0.1 or 0.25 mg of preservative-free morphine. Employing a visual analog scale (no pain to worst pain possible) postoperative pain was assessed at 3,6,12,16 and 24 hours postoperatively. Simultaneous determinations of maternal respiratory rate, heart rate, blood pressure, nausea and vomiting, and pruritus were made. Possible respiratory depressant effects of morphine were assessed by determining the responses to progressive hypercapnia. When pain relief was needed within the first 24 postoperative hours, 8 mg of morphine were given SC, followed by CO2 response determinations at 1.5 and 3.0 hours after injection. Neonatal status was determined by Apgar scores at birth and NACS at 2 and 24 hours after birth.

The maternal and fetal cardiovascular effects of epidural morphine in the sheep model

Interest in the use of epidural narcotics for analgesia has been widespread since the demonstration of opiate receptors in the spinal cord in the mid nineteen-seventies. Recently, several studies have attempted to evaluate the effectiveness of epidural narcotics for the relief of pain in labor and after cesarean section. Using the chronically catheterized maternal-fetal sheep model, we injected 5 mg of preservative-free morphine into the epidural space. No statistically significant changes were observed, neither in maternal or fetal arterial pressure and acid-base status, nor in maternal central venous pressure, systemic and pulmonary vascular resistance, cardiac output, or intrauterine pressure (p greater than 0.05). There was a significant, although small, decrease in maternal heart rate (8%) and uterine blood flow (9%) at 120 minutes (p less than 0.05), and then a return to control values. The maternal levels of morphine peaked at 15 minutes (29 ng/ml) and the fetal levels of morphine peaked at 90 minutes (3 to 4 ng/ml). We conclude that the injection of 5 mg of morphine into the maternal epidural space has no adverse effect on mother or fetus in the sheep model.