Preservative-free Morphine Research Articles

A comparison of continuous epidural infusion and intermittent intravenous bolus doses of morphine in children undergoing selective dorsal rhizotomy

Background and Objectives. Selective dorsal rhizotomy (SDR) is associated with moderate to severe postoperative pain. Although the efficacy of epidural analgesia in this population has been demonstrated, it has not been compared with conventional intravenous (i.v.) analgesia. This prospective study compared the effects of epidural and i.v. morphine regarding postoperative analgesia, side effects, and outcomes in children following SDR. Methods. Twenty-seven children were randomized to receive either epidural or i.v. analgesia. Children in the epidural group had a catheter placed by the neurosurgeon and received preservative-free morphine (Duramorph) 30 μg/kg, followed by an infusion of 3 μg/kg/h for 3 days. Children in the i.v. group received morphine 0.05-0.1 mg/kg intraoperatively, followed by 0.02 mg/kg doses postoperatively administered by nurses via a patient-controlled analgesia device. Results. The epidural group experienced lower pain scores ( P = .04) and fewer muscle spasms ( P ≤ .04), and tolerated activity better ( P ≤ .02) during the early postoperative period than the i.v. group. Side effects were similar between groups, with no respiratory depression in either group. Parents of children in both groups perceived an adequate level of comfort and were very satisfied with the analgesic technique. Additionally, parents believed that their child's postoperative pain was less than anticipated ( P ≤ .01). Conclusions. Both techniques provided effective postoperative analgesia with a similar incidence of side effects; however, our findings suggest that continuous infusions of epidural morphine improved overall comfort with lower pain scores, fewer muscle spasms, and improved tolerance of activity during the initial postoperative period.

Successful Epidural Anesthesia for Cesarean Section for Sextuplets

Successful Epidural Anesthesia for Cesarean Section for Sextuplets

Patient-controlled analgesia using ropivacaine via an intrathecal catheter

Background and Objectives. A 38-year-old woman presented with severe intractable pain in the sacral and perirectal areas secondary to metastatic stage I.B. squamous cell carcinoma of the cervix. Methods. An indwelling epidural catheter was placed to control the patient's symptoms after failure of conservative therapies. Finally, an infusion containing isobaric 0.2% ropivacaine with 0.002% preservative-free morphine and 0.0002% epinephrine was started to treat her pain and preserve motor function to preserve qulaity of life. Results. The patient obtained good pain relief with this regimen and was discharged home. She was able to walk with assistance and maintain good quality of life until her death approximately 7 weeks after the placement of the indwelling epidural catheter. Conclusion. The use of ropivacaine in combination with other analgesics, via an intrathecal catheter for patient-controlled analgesia, was an effective treatment for this patient. In the future, ropivacaine administered epidurally or intrathecally alone, or in combination with other analgesics, may become the local anesthetic of choice due to its preservation of motor function. Certainly, further scientific studies are indicated in the cancer patient population.

Generalized Muscle Rigidity and Hypercarbia with Halothane and Isoflurane

Generalized Muscle Rigidity and Hypercarbia with Halothane and Isoflurane

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.

Simultaneous bilateral percutaneous nephrolithotomy with subarachnoid spinal anesthesia.

We report our experience performing simultaneous bilateral percutaneous nephrolithotomy (SBPN) in four patients with large stone burdens in both kidneys. We modified the previously described approach by combining SBPN with subarachnoid Duramorph (preservative-free morphine sulfate) in an effort to decrease postoperative discomfort and shorten the duration of hospitalization. These patients (study group) were then compared with a contemporary group of four patients with similar bilateral stone burdens who underwent staged bilateral percutaneous nephrolithotomies (PCNs) (control group). The comparison showed a marked advantage in hospital stay (4.8 days for the study group v 11 days for the control group) and postoperative narcotic requirement (27.5 mg of meperidine for the study group v 533 mg for the control group). All four patients were rendered stone free. This method of treatment for large bilateral renal calculi with the addition of subarachnoid Duramorph resulted in less postoperative discomfort, less morbidity, and a more rapid recovery than staged PCN or sandwich PCN/SWL/PCN.

Intra-articular analgesia after arthroscopic knee surgery

One hundred and three patients ASA grades I-II, 16-80 years of age scheduled for arthroscopic meniscectomy were prospectively studied, and randomly allocated to one of four groups: group 1 (n=25): 0.25% bupivacaine (50 mg) intra-articular (IA), group 2 (n=27): 1 mg of 0.1% preservative free morphine chloride in saline, group 3 (n=26): 1 mg of 0.1% preservative free morphine chloride in 0.25% bupivacaine and group 4(n=25): normal saline (0.9%). The volume given was always 20 mL. Ketorolac[Toradol®, 30 mg intra-muscularly (i.m.)] was used as rescue medication; analgesia was assessed using a visual analogue scale (VAS), a verbal rating scale(VRS), supplemental analgesic consumption post-operatively (SAC) and the presence of side effects. Verbal rating scale and visual analogue scale scores showed better pain control in group 1, 20 min after surgery, and in groups 1 and 2 at 4 h and 10 h as well as in the global VAS. In multifactorial analysis no significant differences among groups or side effects was found. pH analysis of the substances used showed no alterations in the basal pH range. The analgesic efficacy of 20 mL of bupivacaine 0.25% is similar to that of 1 mg of morphine in 20 mL of saline 0.9%. The morphine-bupivacaine mixture was no more efficacious than bupivacaine or morphine alone.

Comparison of intrathecal morphine and continuous femoral 3-in-1 block for pain after major knee surgery under spinal anaesthesia

Major knee surgery is associated with moderate or severe post-operative pain. Intrathecal morphine and continuous femoral 3-in-1 block were compared prospectively in 40 patients for pain after major knee surgery under spinal anaesthesia, with 4mL isobaric 0.5% bupivacaine. In a random order, 20 patients received preservative free morphine 0.3 mg mixed with spinal bupivacaine. In 20 patients, following spinal anaesthesia with only bupivacaine, femoral 3-in-1 block was performed post-operatively with 0.5% bupivacaine 2 mg kg−1. The block was continued via a catheter with 0.25% bupivacaine 0.1 mL h−1 kg−1 until the next morning (24 h after induction of spinal anaesthesia). Intramuscular oxycodone was given as a rescue analgesic in all patients. Two patients from the femoral group were excluded due to technical failure. Three patients in the morphine group and one patient in the femoral group did not need any additional oxycodone. In the morphine group on average 2.8 (range 0-7) and in the femoral group 3.2 (0-5) additional doses of oxycodone were needed during the 24 h observation period. The mean pain scores were significantly lower in the morphine group at 9 and 12 h into the 24-h trial. Itching was seen only in the morphine group (40% of the patients). Other side effects were similar in the two groups. All patients were satisfied with their pain therapy. Both intrathecal morphine and femoral 3-in-1 block alone were insufficient for the treatment of severe pain after major knee surgery.

Does intrathecal morphine in the treatment of cancer pain induce the development of tolerance?

This retrospective study was designed to investigate whether chronic lumbar intrathecal administration of morphine leads to the development of opioid tolerance in patients suffering from intractable cancer pain. Between 1978 and 1995, 159 patients with refractory cancer pain were treated with intrathecal morphine in our Multidisciplinary Pain Center. The treatment consisted of preservative-free morphine administered through an access port as a single bolus. In this series of patients (n = 159), the daily doses of intrathecal morphine were determined as a function of duration of follow-up. The mean follow-up period was 95 days (range, 5-909 d), the mean starting daily dose of intrathecal morphine was 2.69 mg (range, 1-7.5 mg), and the mean terminal dose was 7.82 mg (range, 1-80 mg). The results demonstrated that only a moderate increase in daily dose of intrathecal morphine was required during the course of treatment (a two- to threefold increase for a 3-mo period). Furthermore, the dose increment was similar for patients followed up for more or less than 60 days. This increase did not result in any central opioid-related side effects, and the pain was managed satisfactorily. The requirement for a moderate increase in intrathecal opioid doses reflects the development of tolerance but did not limit the patients' ability to obtain adequate analgesia during the course of their painful disease.

Addition of morphine to intra-articular bupivacaine does not improve analgesia following knee joint replacement

In an effort to further decrease postoperative opioid requirements and improve analgesia in patients undergoing elective knee joint replacement, a study was made of the effectiveness of adding morphine to an intra-articular bupivacaine injection given immediately following surgery. In random, double-blind fashion, 75 patients received a 31-mL intra-articular injection consisting of either 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mL normal saline (group BUP), 30 mL 0.5% bupivacaine with 1:200,000 epinephrine and 1 mg (1 mL) preservative-free morphine (group BUP-MORPH), or 30 mL normal saline with 1:200,000 epinephrine and 1 mg preservative-free morphine (group MORPH). Postoperative analgesia was supplied by patient controlled analgesia (PCA) with morphine. Patients were assessed at 1, 2, 4, and 24 hours for pain (visual analog and verbal rating scales), morphine utilization, and side effects. Knee range of motion was measured before operation and at hospital discharge. There was no difference among the three groups in PCA morphine requirements, pain scores by either scale, range of motion, or incidence of side effects, including somnolence, urinary retention, nausea and vomiting, and pruritus. The addition of 1 mg morphine to an intra-articular injection of 30 mL 0.5% bupivacaine with 1:200,000 epinephrine given at wound closure does not improve analgesia in patients undergoing elective knee joint replacement.

Cardiopulmonary Bypass in a Patient with Moyamoya Disease

Cardiopulmonary Bypass in a Patient with Moyamoya Disease

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.

Spinal Anesthesia for Cesarean Section in a Case of Pemphigus Foliaceous

Spinal Anesthesia for Cesarean Section in a Case of Pemphigus Foliaceous

Off-Label Use of Ketorolac

In Response: We were initially concerned about the possible adverse effects of alcohol contained in ketorolac (10% wt/vol) on articular cartilage. However, in our study [1], we diluted ketorolac (60 mg/2 mL) in a volume of 30 mL 0.25% bupivacaine. The resultant alcohol content (0.7% wt/vol) is less than that of sterile triamcinolone acetonide suspension (0.9% wt/vol) (Steris Laboratories, Phoenix, AZ), which has Food and Drug Administration approval for intraarticular administration. Furthermore, clinical studies using in vitro bovine cartilage have revealed that ketorolac has no effect on degradation of cartilage matrix [2]. In fact, ketorolac appears to have a protective effect on articular cartilage by preventing the release of cytokines, including interleukin-1, which has been shown to play a pivotal role in triggering excessive cartilage degradation under inflammatory conditions. In our most recent study with intraarticular ketorolac [3], we have demonstrated that equally effective analgesia can be obtained with intraarticular morphine. We have thus recommended that clinicians use intraarticular bupivacaine along with (the less expensive) preservative-free morphine. Due to the cost, we do not recommend the routine "off-label" use of intraarticular ketorolac; however, we do believe that it can be safely administered in the intraarticular space for those patients in whom morphine is medically contraindicated. Scott S. Reuben, MD Neil R. Connelly, MD Department of Anesthesiology Baystate Medical Center and the Tufts University School of Medicine Springfield, MA 01199

Experiences with morphine injected into the subarachnoid space in sheep.

The effects of morphine (M), 0.1 mg/kg, administered into the lumbosacral subarachnoid space of sheep used for experimental stifle surgery, were investigated. In a pilot study, preservative-free morphine was administered to three sheep, morphine containing preservatives to two sheep, and saline (S) to one sheep. After recovery from anesthesia, all five sheep administered M displayed rear limb weakness. One sheep, which had received morphine containing preservatives, also licked and chewed incessantly at its flank and hindquarters during recovery. A group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on recovery from general anesthesia and hindlimb orthopedic surgery. Eight sheep received M, eight sheep received S, and eight sheep had a needle placed in the subarachnoid space without any injection (N). Times from end of anesthesia to standing varied greatly and did not differ significantly among groups (P = .73), with M sheep averaging 119 minutes; S sheep, 87 minutes; and N sheep, 83 minutes. One sheep administered M licked and chewed at its hindquarters during recovery. Another group of 24 sheep was used to study the effects of morphine containing preservatives, injected intrathecally, on postoperative lameness. Treatments were as described previously. Sheep were videotaped intermittently for 36 hours after surgery, and each sheep was scored as follows: 0 = not lame; 1 = slightly lame; and 2 = very lame. The average lameness scores, which did not differ significantly among groups (P = .21), were: M sheep, 1.07; S sheep, 0.81; and N sheep, 0.68. One sheep administered M displayed extensor spasms of the hindlimbs, and could not stand until several hours after surgery. We conclude that subarachnoid morphine at the dosage used produces no apparent benefit in sheep which have had stifle surgery, and in fact may cause detrimental side effects, such as hindlimb weakness, and pruritus or irritation of the hindquarters.

Intrathecal infusion systems for treatment of chronic low back and leg pain of noncancer origin.

In this study, 26 patients (average age, 44.3 years) with chronic noncancer pain averaging 115 months' duration had implantation of an infusion pump with intrathecal catheter placement. In general, preservative-free morphine sulfate was used. Average follow-up was 23 months. Measurements of pain reduction, activity improvement, oral medication use, and overall satisfaction by patient, spouse, and clinic staff were obtained. Of the 26 patients, 20 noted a good or excellent outcome. Average daily dosage of intrathecal morphine increased over time by approximately sevenfold. Subjective pain levels decreased an average of 59%, and daily functioning increased 50%. No postoperative complications were noted, but 11 patients required additional surgery (9 for catheter complications). These data support chronic spinal opiate therapy as an option for safe and long-term management of noncancer pain.

Intrathecal morphine for analgesia in children undergoing selective dorsal rhizotomy

Selective dorsal root rhizotomy is performed for relief of spasticity in children with cerebral palsy. Postoperative pain relief can be provided by intrathecal morphine administered at the time of the procedure. We sought to define an optimal dose of intrathecal morphine in children undergoing selective rhizotomy, through a randomized, double-blinded prospective trial. After institutional approval and parental written informed consent, 27 patients, ages 3–10 years, were randomized to receive 10, 20, or 30 μg·kg −1 (Groups A, B, and C, respectively) of preservative-free morphine administered intrathecally by the surgeon after dural closure. Postoperatively vital signs, pulse oximetry, and pain intensity scores were recorded hourly for 24 hr. Supplemental intravenous morphine was administered postoperatively according to a predetermined schedule based on pain scores. There was considerable individual variability in the time to initial morphine dosing and cumulative supplemental morphine dose. Time to first supplemental morphine dose was not different between groups. When compared to Groups A and B, cumulative 6-hr supplemental morphine dose wa significantly lower in Group C (38.6 ± 47 μg versus 79.1 ± 74 and 189.6 ± 126 for Groups A and B, respectively). By 12 hr, cumulative supplemental morphine dose was similar in Groups A and C. Group B consistently had a higher supplemental dose requirement than Groups A and C at 6, 12, and 18 hr. By 24 hr, there was no difference in cumulative dose among groups. Postoperative pain scores and the incidence of respiratory events, nausea, vomiting, and pruritus were comparable among groups. These data suggest that intrathecal morphine at 30 μg·kg −1 provides the most intense analgesia at 6 hr following selective dorsal root rhizotomy, but was otherwise comparable to the 10 μg·kg −1 dose.

Lumbar epidural morphine infusions for children undergoing cardiac surgery

To determine whether outcomes and costs in children undergoing cardiac surgery are affected by the method of postoperative pain management. Retrospective, case control. Tertiary care children's hospital in a university setting. Two groups of children undergoing cardiac surgery for palliation or repair of congenital heart disease oer a 21-month period between January 1993 and September 1994. Lumbar epidural morphine infusions (LEM) in one group, and IV opioid (IVO) medication in the other for postoperative pain control. Hospital courses of 27 LEM patients and 27 IVO patients were analyzed. In LEM patients, epidural catheters were placed following anesthetic induction, but before anticoagulation. A bolus of 50 micrograms/kg of preservative-free morphine sulfate was administered through the catheter, followed by a continuous infusion at 3 to 4 micrograms/kg/h for 22 to 102 (median, 46) hours postoperatively. The IVO patients received 50 micrograms/kg, IV, of fentanyl before incision followed by a continuous infusion at 0.3 microgram/kg/min. The fentanyl infusion rate was decreased to 0.1 microgram/kg/min postoperatively and maintained for 24 hours. Although the LEM group was demographically similar to the IVO group, times to tracheal extubation, transfer from the intensive care unit, and resumption of regular diet were significantly shorter in LEM patients. LEM and IVO patients received similar amounts of fentanyl during surgery (10.4 +/- 19.3 micrograms/kg/h v 13.7 +/- 8.1 micrograms/kg/h, p = 0.4). However, during postoperative recovery, LEM patients who were extubated late received significantly less supplemental opioid medication than IVO patients extubated late during the first 5 postoperative days. No complications related to dural puncture, bleeding into the epidural space, or respiratory depression were encountered. Pruritus and nausea/vomiting were the most commonly reported morbidities in both groups. Fifty-six percent (15/27) of LEM patients and 41% of IVO patients reported pruritus (p = 0.4). There was no significant difference in the incidence of nausea and vomiting between the groups (34% v 30%, respectively). Given the present methodologic limitations, the authors found improved outcomes only in LEM patients extubated late compared with IVO patients. Randomized, prospective studies to evaluate this conclusion and to determine the comparative efficacy and safety of LEM infusions are in progress.

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.