Pathophysiology of opioid tolerance and clinical approach to the opioid-tolerant patient.

The physiologic basis for opioid tolerance has been elucidated, resulting in a better understanding of this problem. As a result of this ongoing effort, patients exhibiting opioid tolerance can now expect better pain management both in the postoperative period and during the course of their treatment. This article outlines the pathophysiology of opioid tolerance and a practical clinical approach to this problem.

An in vitro study of dural lesions produced by 25-gauge Quincke and Whitacre needles evaluated by scanning electron microscopy.

BACKGROUND AND OBJECTIVES: A study using scanning electron microscopy showed that although the laminas forming the dura mater are concentric and parallel to the surface of the medulla, the fiber layers' orientations are different in each sub-lamina, dispelling the conventional knowledge that all the fibers of the dura are arranged in a parallel direction. Thus, this study evaluated the dural lesions produced by Whitacre and Quincke spinal needles in the external and internal surface of the dura mater of the lower spine area in an attempt to gain more insight into the pathophysiology of postdural puncture headaches (PDPH). METHODS: The T11-L4 dural membranes from 5 fresh (immediately after extraction of organs for transplantation), male patients declared brain dead, ages 23, 46, 48, 55, and 60 years, were excised by anterior laminectomy. Morphologic orientation of the membrane and normal pH were maintained with an apparatus designed for this purpose. One hundred punctures (20 on each sample) at 90-degree angles were done with a new needle each time, 50 with 25-gauge Whitacre and 50 with 25-gauge Quincke needles. Half of the punctures with the Quincke needles were done with the bevel in parallel direction to the axis of the spinal cord, and the rest with the bevel perpendicular to it. Fixation in solutions of 2.5% glutaraldehyde phosphate buffer, followed by dehydration with acetone, was done 15 minutes after the punctures. After acetone was removed at ideal conditions of temperature and pressure, the specimens were then metallized with carbon followed by gold and inspected under a scanning electron microscope. RESULTS: Twenty-five of the Whitacre and 23 of the Quincke punctures were found for evaluation. There were no differences in the cross-sectional area of the punctures produced by the Whitacre or Quincke needles on the dura. The area of the dural lesions produced by 25-gauge Quincke needles, 15 minutes after they have been withdrawn, was 0.023 mm2 (confidence interval [CI] 95%, 0.015 to 0.027) in the external aspect (epidural surface) and 0.034 mm2 (CI 95%, 0.018 to 0.051) in the internal aspect (arachnoid surface) of the dural sac. The area of the lesions produced by the 25-gauge Whitacre needles was 0.026 mm2 (CI 95%, 0.019 to 0.032) and 0.030 mm2 (CI 95%, 0.025 to 0.036) in the external and internal surfaces of the dural sac, respectively. There were no significant differences in the cross-sectional areas of the punctures produced by the 25-gauge Whitacre or 25-gauge Quincke needles. Moreover, with Quincke needles the dural lesions closed in an 88.3% (CI 95%, 86.3 to 92.4) and 82.7% (CI 95%, 74.1 to 90.9) of their original sizes in the epidural and arachnoid surfaces, respectively. With Whitacre needles, the closure occurred in an 86.8% (CI 95%, 83.8 to 90.3) and 84.8% (CI 95% 81.7 to 87.3) in the dural and arachnoid surfaces, respectively. However, there were differences in the morphology of the lesions. The Whitacre needles produced coarse lesions with significant destruction in the dura's fibers while the Quincke needles produced a 'U'-shaped lesion (flap) that mimics the opened lid of a tin can, regardless of the tip's direction. CONCLUSIONS: The needles produced lesions in the dura with different morphology and characteristics. Lesions with the Quincke needles resulted in a clean-cut opening in the dural membrane while the Whitacre needle produced a more traumatic opening with tearing and severe disruption of the collagen fibers. Thus, we hypothesized that the lower incidence of PDPH seen with the Whitacre needles may be explained, in part, by the inflammatory reaction produced by the tearing of the collagen fibers after dural penetration. This inflammatory reaction may result in a significant edema which may act as a plug limiting the leakage of cerebrospinal fluid.

Critical evaluation of chemical neurolysis of the sympathetic axis for cancer pain.

BACKGROUND: Patients with pain caused by cancer frequently experience visceral pain. In addition to oral pharmacologic therapy to manage pain, neurolytic blocks of the sympathetic axis are also effective in controlling visceral cancer pain. METHODS: Four types of neurolytic blocks (interpleural phenol, celiac plexus, superior hypogastric plexus, and ganglion impar) used in the treatment of visceral cancer pain are reviewed. RESULTS: Several studies have documented the efficacy of neurolytic blocks in reducing pain intensity and opioid consumption. However, the narrow risk-benefit ratio associated with neurolysis techniques requires knowledge of the implications associated with the different neurolytic blocks to minimize undesirable effects. CONCLUSIONS: Neurolysis of the sympathetic axis has been shown to be an effective and safe approach to treat visceral pain in cancer patients and should be incorporated in the armamentarium of the pain specialist as a useful adjunct to oral pharmacologic therapy.

Evaluation of peripheral morphine analgesia for lumpectomy and axillary node dissection: a randomized, double-blind, placebo-controlled study.

BACKGROUND AND OBJECTIVES: Morphine may elicit potent antinociceptive effects by binding and activating peripheral opioid receptors. However, the results in clinical studies have varied. We examined the postoperative analgesic effects of incisional morphine in patients undergoing lumpectomies and axillary node dissections for breast cancer. For this purpose, a concentration of morphine within the range (0.25-0.6%) of those utilized in previous studies for postarthroscopy analgesia was chosen (0.6%). METHODS: Forty-five patients scheduled to undergo a lumpectomy and axillary node dissections for breast cancer were enrolled in this study after receiving Ethics Committee approval and patient consent. Patients were randomized to undergo irrigation of the surgical sites for 5 minutes prior to skin closure with 6 mg morphine diluted in 100 mL 0.9% normal saline (NS) and placebo intramuscular (i.m.) (peripheral MS group), 100 mL of 0.9% NS alone and placebo i.m. (placebo group), or 100 mL of 0.9% NS and 6 mg morphine i.m. in the deltoid muscle (i.m. MS group) in a double-blind fashion. In the postanesthesia care unit, patients received fentanyl via a patient-controlled analgesia (PCA) device programmed to deliver 25 microg every 10 minutes to a maximum dose of 150 microg/h. Patients were evaluated for pain using a visual analog scale card from 0-10, opioid consumption, and incidences of side effects at 2, 6, 12, 18, and 24 hours after surgery. RESULTS: All patients had adequate analgesia at rest and during arm movement with visual analog pain scores (VAPS) <3/10 throughout the study period. There were no significant differences in demographics, total fentanyl consumption (500 vs. 475 vs 933 microg, respectively; P = .2), VAPS at rest and during arm movement as well as fentanyl consumption at the different evaluation points among the three groups. CONCLUSIONS: These results suggest that under the conditions of the study protocol, there is no value in utilizing morphine in solution at the surgical site for postoperative lumpectomy and axillary node dissection analgesia.

Neurolytic superior hypogastric plexus block for chronic pelvic pain associated with cancer.

BACKGROUND AND OBJECTIVES: Neurolytic superior hypogastric plexus block has been shown to be safe and effective in selected cancer patients. A large cohort of patients was studied to evaluate the continued efficacy and safety of this block in cancer patients with advanced disease. METHODS: A total of 227 pelvic pain patients with gynecological, colorectal, or genitourinary cancer who experienced poor pain control due to either progression of disease or to untoward side effects were enrolled in this study during a 3-year period. All pain patients receiving oral opioids were eligible to participate. A bilateral percutaneous neurolytic superior hypogastric plexus block with 10% phenol was performed 1 day after a successful diagnostic block with 0.25% bupivacaine. RESULTS: All patients reported a visual analog scale (VAS) pain score of 7-10/10 before the block. A positive response to a diagnostic block was obtained in 159 patients (79%). Overall, 115 patients of the 159 patients who responded to a diagnostic block (72%, 95% confidence interval of 65-79%) had satisfactory pain relief (VAS < 4/10), 99 (62%) after one block, and 16 (10%) after a second block. The remaining 44 patients (28%) had moderate pain control (VAS 4-7/10) after two blocks and received oral pharmacological therapy and epidural analgesic therapy with good results. Both groups experienced significant reductions in oral opioid therapy after the neurolytic blocks. No additional blocks were required by patients who had a good response during a follow-up period of 3 months. No complications related to the block were detected. CONCLUSIONS: Neurolytic superior hypogastric plexus block provided both effective pain relief and a significant reduction in opioid usage (43%) in 72% of the patients who received a neurolytic block. Overall, this represents 51% of the patients enrolled in the study. Poor results should be expected in patients with extensive retroperitoneal disease overlying the plexus because of inadequate spread of the neurolytic agent.

Postoperative epidural opioid analgesia: what are the choices?

The administration of hydrophilic opioids via a continuous infusion results in selective spinal analgesia with a low incidence of side effects. Lipophilic opioids may also be associated with spinal effects. However, the doses required to produce postoperative analgesia also produce plasma concentrations within the MEAC. Thus, in clinical practice it may not be possible to limit epidural doses of lipophilic opioids to those associated with spinal analgesia. Regardless of the mechanism of action, epidural administration of lipophilic opioids may offer no clinical advantages over the IV route. Notwithstanding, epidural administration of small doses of lipophilic opioids in combination with local anesthetics may offer significant clinical advantages over systemic administration of opioids alone. Dose-ranging studies will be necessary to determine the ideal concentrations of opioids and local anesthetics, as well as the ratios of the two drugs to obtain optimal analgesia with minimal incidence of side effects.

Bowel function recovery after radical hysterectomies: thoracic epidural bupivacaine-morphine versus intravenous patient-controlled analgesia with morphine: a pilot study.

STUDY OBJECTIVE: To determine if the use of continuous epidural bupivacaine-morphine in the perioperative period is associated with a significant decrease in the recovery time of postoperative ileus when compared with parenteral morphine administration. DESIGN: Prospective (quality of analgesia) and retrospective (bowel function recovery), nonrandomized study. SETTING: Inpatient gynecology-oncology patients at a university-affiliated tertiary cancer center hospital. PATIENTS: 68 women who experienced uncomplicated radical hysterectomies for cancer. INTERVENTIONS: Intraoperative epidural-general anesthesia or general anesthesia only was administered. Postoperative continuous epidural analgesia with bupivacaine-morphine and intravenous (IV) morphine via patient-controlled analgesia (PCA). Both forms of therapy were titrated to provide patients with a dynamic visual analog pain score of 5 or less on a 10-point scale throughout the study period. Patients were weaned from infusions when pain scores remained at less than 5 for 12 hours and no breakthrough medication was used. MEASUREMENTS AND MAIN RESULTS: Rest and dynamic pain scores, time of first flatus, length of nasogastric therapy, time to solid food intake, daily and total morphine requirements and length of hospitalization were recorded. The epidural group required fewer days of nasogastric therapy (4 +/- 3 versus 8 +/- 2 days, p = 0,0001), tolerated solid foods sooner (6 +/- 2 versus 11 +/- 3 days, p < 0.0001), and had a shorter hospitalization time (10 +/- 3 versus 14 +/- 4 days, p = 0.0001) when compared with the PCA group. CONCLUSIONS: The use of thoracic epidural bupivacaine-morphine results in a decrease in the duration of postoperative ileus, which was associated with earlier hospital discharge.

The influence of preoperative concentrations of beta-endorphin and met-enkephalin on the duration of analgesia after transurethral resection of prostate.

beta-Endorphin (beta-EP) and methionine-enkephalin (M-EK) are endogenous peptides that play a role in the modification of pain perception and analgesia threshold. In order to understand more about pathophysiology of pain in association with neuroaxial blocks, we evaluated cerebrospinal fluid (CSF) concentrations of beta-EP and M-EK prior to spinal anesthesia (SA) in patients undergoing transurethral resection of prostate (TURP) to determine the correlation between preanesthesia concentrations and the duration of postoperative analgesia and opioid requirements. Twenty-five healthy patients undergoing TURP under SA were enrolled. beta-EP and M-EK were measured with a competitive radioimmunoassay. Mean preoperative beta-EP and M-EK concentrations were 153 +/- 44 and 38 +/- 5 pg/mL, respectively. Those with beta-EP concentrations > 153 pg/mL had significantly longer analgesia (P < 0.01), and lower utilization of morphine in the first postoperative day (P < 0.01). Moreover, patients with milder postoperative pain (visual analog scale score < 4/10) had significantly higher beta-EP concentrations (P < 0.01). A similar correlation was not found with M-EK values. These data suggest that preoperative CSF beta-EP, but not M-EK, concentrations correlate with the duration and quality of postoperative analgesia, as well as opioid requirements after spinal anesthesia.

Postoperative myocardial ischemia: epidural versus intravenous patient-controlled analgesia. A pilot project.

BACKGROUND AND OBJECTIVES: Continuous postoperative epidural analgesia with bupivacaine (BUP) and morphine (MS) may be associated with a decreased incidence of postoperative myocardial ischemia (ISCH) and infarction (MI). This study evaluated the incidence of ISCH and MI in patients with two or more risk factors for coronary artery disease (CAD) who were admitted to the ICU after upper abdominal surgery for cancer. METHODS: During a 1-year period, 198 patients were studied for the incidence of ISCH and MI in a prospective, nonrandomized fashion. The epidural group (EPI, n = 110) received continuous epidural anesthesia by injection at the T7-9 interspaces with 0.5% BUP/0.013% MS and light general anesthesia followed by 0.1% BUP/0.01% MS epidural analgesia for 5-7 days. The general anesthesia group (GEN, n = 88) received a balanced technique followed by intravenous patient-controlled analgesia with 0.1% MS for 5-7 days. All patients had preoperative and postoperative 12 lead ECGs every 6 hours on the first 3 postoperative days. Patients with ECG changes consistent with myocardial ischemia had creatine kinase levels with isoenzymes drawn every 8 hours. RESULTS: There were no differences in age, sex, number of cardiac risk factors, number taking anti-anginal medication, preoperative heart rate (75 +/- 5 [EPI] vs. 73 +/- 4 [GEN]), and incidence of preoperative or intraoperative ischemia between the two groups. All patients had adequate analgesia. Postoperatively, patients in the EPI group had a lower incidence of tachycardia (15 [14%] vs. 58 [65%], P < .00001), ischemia (5 [5%] vs. 15 [17%], P < .004), and infarction (0 vs. 3 [20% of patients with ischemia]). All episodes of ischemia were silent and occurred more frequently during the first 36 hours postoperatively (14 episodes or 72%). Overall 60% of the ISCH episodes were associated with tachycardia (5/5 in the EPI group and 7/15 in the GEN group). There were no deaths in either group. CONCLUSIONS: These preliminary results suggest that epidural anesthesia and analgesia may decrease the incidence of postoperative tachycardia, ischemia, and possibly infarction in patients undergoing upper abdominal procedures.

Epidural analgesia versus intravenous patient-controlled analgesia. Differences in the postoperative course of cancer patients.

BACKGROUND AND OBJECTIVES: This study evaluated 462 consecutive surgical cancer patients who underwent uncomplicated surgeries of the thorax or abdomen, or both, of more than 3 hours duration between 1989 and 1991. METHODS: Patients received either epidural analgesia (EA group) with 0.1% bupivacaine, 0.01% morphine sulfate after combined general-epidural anesthesia, or parenteral morphine therapy via intravenous patient-controlled analgesia (IV-PCA) after balanced general anesthesia after the operation. Patients in both the EA (n = 352) and IV-PCA (n = 100) groups were compared for demographics, length of surgical intensive care unit (SICU), and hospital stays. Moreover, the same comparisons were performed when patients were allocated into surgical subgroups: thoracic (TH), upper abdominal (UA), lower abdominal (LA), radical hysterectomies (RH), and RH with colon resection (RHCR). RESULTS: No differences existed with respect to age or sex between the EA and IV-PCA groups. All patients reported adequate dynamic pain control as evaluated with visual analog pain scores (VAS < 4/10), during the treatment periods (5 +/- 3 versus 5 +/- 2 days, EA versus IV-PCA). Overall, 262 (58%) patients were admitted to the SICU after the operation, 205 (58%) from the EA group and 57 (57%) from the IV-PCA group. Patients in the EA group required less ventilatory support than did those in the IV-PCA group (0.5 +/- 0.8 versus 1.2 +/- 0.9 days, P < .05). Patients in the EA group also spent less time in both the SICU (1.3 +/- 0.8 versus 2.8 +/- 0.6 days, P < .05) and in the hospital (11 +/- 3 versus 17 +/- 5 days, P < .05) than did their counterparts in the IV-PCA group. Significant differences were also found when subgroup comparisons were made. CONCLUSIONS: The use of both analgesic techniques was associated with satisfactory postoperative pain control. However, patients receiving epidural anesthesia and analgesia experienced faster recovery as judged by shorter mechanical ventilation time, and decreased SICU and hospital stays, resulting in significantly lower hospitalization costs. The use of perioperative epidural techniques should be considered to expedite recovery of surgical patients, and has the added benefit of being cost effective by reducing hospital stays.