Gavin Martin

Forty-eight hours of postoperative pain relief after total hip arthroplasty with a novel, extended-release epidural morphine formulation

Background: Epidural morphine has proven analgesic efficacy in the postoperative period and is widely used. This study evaluated the efficacy of extended-release epidural morphine (EREM; DepoDur; Endo Pharmaceuticals Inc., Chadds Ford, PA; SkyePharma, Inc., San Diego, CA) in providing pain relief for 48 h after surgery. Methods: Patients (n = 200) scheduled to undergo total hip arthroplasty were randomized to receive a single dose of 15, 20, or 25 mg EREM or placebo. After surgery and after asking for pain medication, patients had access to intravenous patient-controlled analgesia fentanyl for breakthrough pain as needed. Postoperative intravenous patient-controlled analgesia fentanyl use, time to first postoperative fentanyl use, pain intensity at rest and with activity, patient and surgeon ratings of pain control, and adverse events were recorded. Results: All EREM dosages reduced the mean (± SD) fentanyl use versus placebo (510 ± 708 vs. 2,091 ± 1,803 &mgr;g; P < 0.0001) and delayed the median time to first dose of fentanyl (21.3 vs. 3.6 h; P < 0.0001). All EREM groups had significantly improved pain control at rest through 48 h postdose (area under the curve [0–48 h]) compared with placebo (P < 0.0005). More EREM-treated patients rated their pain control as good or very good compared with placebo (at 24 h: 90 vs. 65%, P < 0.0001; at 48 h: 83 vs. 67%, P < 0.05). No supplemental analgesia was needed in 25% of EREM-treated patients and 2% of placebo-treated patients at 48 h (P < 0.05). The safety profile of EREM was consistent with that of other epidurally administered opioid analgesics. Conclusions: EREM provided significant postoperative pain relief over a 48-h period after hip surgery, without the need for indwelling epidural catheters.

A Comparison of Depodur™, a Novel, Single-Dose Extended-Release Epidural Morphine, with Standard Epidural Morphine for Pain Relief After Lower Abdominal Surgery

In this randomized, controlled, dose-ranging study, we evaluated the analgesic efficacy of a novel single-dose extended-release epidural morphine (Depodur™) in patients undergoing lower abdominal surgery. Five-hundred-forty-one patients were randomly assigned to one of six epidural treatments administered approximately 30 min before surgery. The 6 treatments were 5 mg of standard epidural morphine sulfate (MS) (active comparator); 5 mg of single-dose extended-release epidural morphine (EREM) (dose control); and 10, 15, 20, and 25 mg of single-dose EREM. The main study objective was to assess the efficacy of single-dose EREM 10, 15, 20, or 25 mg versus single-dose EREM 5 mg for the management of postoperative pain. This was done by plotting a linear dose-response relationship to assess postoperative IV patient-controlled analgesia (PCA) fentanyl consumption for breakthrough pain for 48 h after surgery. Secondary safety and efficacy analyses compared the 10-, 15-, 20-, and 25-mg single-dose EREM groups with the 5-mg single-dose EREM group and compared each single-dose EREM group with 5 mg of MS. As shown by the dose-response relationship, there was a dose-related reduction in the use of postoperative IV fentanyl through 48 h (estimated slope, −22.2; P = 0.0002). Patients treated with 10, 20, and 25 mg of single-dose EREM used significantly less IV fentanyl (mean ± sd: 995 ± 987 &mgr;g, P = 0.0446; 972 ± 982 &mgr;g, P = 0.0221; and 683 ± 620 &mgr;g, P < 0.0001, respectively) through 48 h after surgery compared with the 5-mg single-dose EREM group (1218 ± 894 &mgr;g). At 48 h postdose, significantly more single-dose EREM patients (13%) than MS patients (2%) had required no IV fentanyl (P < 0.01). Although all treatment groups had access to PCA fentanyl and there was more frequent PCA fentanyl use in the MS group, patients in the single-dose EREM 15, 20, and 25 mg groups reported significantly lower pain-intensity scores and greater satisfaction with their pain relief. Overall, single-dose EREM was well tolerated, with 97% of adverse events rated as mild to moderate. As expected, the adverse events reported were consistent with those of other epidural opioids (i.e., nausea, vomiting, pruritus, and hypotension). In conclusion, this controlled study demonstrated that single-dose EREM can provide up to 48 h of postoperative analgesia, but supplementation for breakthrough pain is still required in most patients. Within the context of this study, the side effect profile of single-dose EREM was acceptable and predictable.

Evaluation of a Single-Dose, Extended-Release Epidural Morphine Formulation for Pain After Knee Arthroplasty

BACKGROUND DepoDur is a single-dose, extended-release epidural morphine formulation designed to provide forty-eight hours of pain relief. The drug offers potential advantages over continuous epidural infusions, particularly in patients being treated with anticoagulation therapy. The purpose of this study was to evaluate the efficacy and safety of single-dose epidural DepoDur for pain control following knee arthroplasty. METHODS In this multicenter, randomized, double-blind, parallel-group study, patients were randomized to receive a single-dose of DepoDur (20 or 30 mg) or a sham epidural injection thirty minutes before administration of general or regional anesthesia for knee arthroplasty. At their first request for postoperative analgesia, patients who had received DepoDur were given an intravenous bolus of hydromorphone followed by placebo patient-controlled analgesia. Patients who had received the sham epidural were given an intravenous bolus of morphine followed by patient-controlled analgesia with morphine. Patient ratings of pain intensity at rest and with activity, their rating of overall pain control, and postoperative opioid use were recorded. The ability to tolerate physical therapy, the range of motion of the knee, and the need for physical support were assessed as well. Adverse events and vital signs were recorded. RESULTS Of 168 patients randomized to receive the 20-mg injection of DepoDur, the 30-mg injection of DepoDur, or the sham epidural injection, fifty-one, fifty-eight, and fifty-five patients, respectively, were included in the efficacy analysis. Compared with the patients treated with intravenous patient-controlled analgesia with morphine, the patients treated with DepoDur had significantly reduced mean pain-intensity-recall scores during the four to eight, four to twelve, four to twenty-four, and four to thirty-hour postdose intervals (p < 0.05 for all comparisons). The patients treated with DepoDur used approximately a threefold lower amount of postoperative opioids in total, with a significant percentage requiring no supplemental opioids. Adverse events common to all groups were nausea (78%), pyrexia (46%), vomiting (43%), pruritus (43%), and hypotension (36%). Respiratory depression was the most common serious adverse event, with serious respiratory depression observed in four DepoDur-treated patients, who were more than sixty-five years of age. CONCLUSIONS With appropriate patient selection and monitoring, perioperative single-dose epidural DepoDur was a safe and effective analgesic alternative to postoperative intravenous patient-controlled analgesia following knee arthroplasty, with younger patients benefiting from the 20-mg dose. Additional studies of 10 to 15-mg doses for older patients are warranted.

Central nervous system toxicity following the administration of levobupivacaine for lumbar plexus block: A report of two cases.

Background and Objectives Central nervous system and cardiac toxicity following the administration of local anesthetics is a recognized complication of regional anesthesia. Levobupivacaine, the pure S(-) enantiomer of bupivacaine, was developed to improve the cardiac safety profile of bupivacaine. We describe 2 cases of grand mal seizures following accidental intravascular injection of levobupivacaine. Case Report Two patients presenting for elective orthopedic surgery of the lower limb underwent blockade of the lumbar plexus via the posterior approach. Immediately after the administration of levobupivacaine 0.5% with epinephrine 2.5 μg/mL, the patients developed grand mal seizures, despite negative aspiration for blood and no clinical signs of intravenous epinephrine administration. The seizures were successfully treated with sodium thiopental in addition to succinylcholine in 1 patient. Neither patient developed signs of cardiovascular toxicity. Both patients were treated preoperatively with β-adrenergic antagonist medications, which may have masked the cardiovascular signs of the unintentional intravascular administration of levobupivacaine with epinephrine. Conclusions Although levobupivacaine may have a safer cardiac toxicity profile than racemic bupivacaine, if adequate amounts of levobupivacaine reach the circulation, it will result in convulsions. Plasma concentrations sufficient to result in central nervous system toxicity did not produce manifestations of cardiac toxicity in these 2 patients.

Reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia: sugammadex versus neostigmine.

BackgroundAcetylcholinesterase inhibitors cannot rapidly reverse profound neuromuscular block. Sugammadex, a selective relaxant binding agent, reverses the effects of rocuronium and vecuronium by encapsulation. This study assessed the efficacy of sugammadex compared with neostigmine in reversal of profound vecuronium-induced neuromuscular block under sevoflurane anesthesia.MethodsPatients aged ≥18 years, American Society of Anesthesiologists class 1-4, scheduled to undergo surgery under general anesthesia were enrolled in this phase III, multicenter, randomized, safety-assessor blinded study. Sevoflurane anesthetized patients received vecuronium 0.1 mg/kg for intubation, with maintenance doses of 0.015 mg/kg as required. Patients were randomized to receive sugammadex 4 mg/kg or neostigmine 70 μg/kg with glycopyrrolate 14 μg/kg at 1-2 post-tetanic counts. The primary efficacy variable was time from start of study drug administration to recovery of the train-of-four ratio to 0.9. Safety assessments included physical examination, laboratory data, vital signs, and adverse events.ResultsEighty three patients were included in the intent-to-treat population (sugammadex, n = 47; neostigmine, n = 36). Geometric mean time to recovery of the train-of-four ratio to 0.9 was 15-fold faster with sugammadex (4.5 minutes) compared with neostigmine (66.2 minutes; p < 0.0001) (median, 3.3 minutes with sugammadex versus 49.9 minutes with neostigmine). No serious drug-related adverse events occurred in either group.ConclusionsRecovery from profound vecuronium-induced block is significantly faster with sugammadex, compared with neostigmine. Neostigmine did not rapidly reverse profound neuromuscular block (Trial registration number: NCT00473694).

A New Teaching Model for Resident Training in Regional Anesthesia

The adequacy of resident education in regional anesthesia is of national concern. A teaching model to improve resident training in regional anesthesia was instituted in the Anesthesiology Residency in 1996 at Duke University Health System. The key feature of the model was the use of a CA-3 resident in the preoperative area to perform regional anesthesia techniques. We assessed the success of the new model by comparing the data supplied by the Anesthesiology Residency to the Residency Review Committee for Anesthesiology for the training period July 1992–June 1995 (pre-model) and the training period July 1998–June 2001 (post-model). During the 3-yr training period, the pre-model CA-3 residents (n = 12) performed a cumulative total of 80 (58–105) peripheral nerve blocks (PNBs), 66 (59–74) spinal anesthetics, and 133 (127–142) epidural anesthetics. The CA-3 post-model residents (n = 10) performed 350 (237–408) PNBs, 107 (92–123) spinal anesthetics, and 233 (221–241) epidural anesthetics (P < 0.0001). All results are reported as median (interquartile range). We conclude that our new teaching model using our CA-3 residents as block residents in the preoperative area has increased their clinical exposure to PNBs.

Posterior Capsular Injections of Ropivacaine During Total Knee Arthroplasty: A Randomized, Double-Blind, Placebo-Controlled Study

We investigated the hypothesis that a posterior capsular injection of ropivacaine would improve pain and accelerate functional recovery after total knee arthroplasty in a randomized, double-blind, placebo-controlled study design. Sixty-six patients received a standardized multimodal anesthesia protocol that included a femoral nerve block. Twenty milliliters of either saline (control) or ropivacaine (study group) was injected into the posterior capsule. Pain and function outcomes were recorded prospectively at 4, 8, 12, and 24 hours postinjection. Significantly more patients in the study group were able to perform a straight-leg raise at 8 and 12 hours. In addition, significantly more patients in the control group had a numeric pain score higher than 7/10 (severe pain) at the 12-hour evaluation. Other parameters of pain or functional recovery were not significantly different between the 2 groups. Posterior capsular injection did not improve the pain or accelerate the functional recovery after 12 hours in patients also receiving a femoral nerve block for pain control after total knee arthroplasty.

A practical guide to commonly performed ultrasound-guided peripheral-nerve blocks.

Purpose of review Regional anesthesia has experienced a tremendous renaissance of interest over the past several years. Much of this renewed enthusiasm among clinicians is due to the increased usage of ultrasound guidance for peripheral-nerve blocks. This review serves as a useful foundation for the most commonly employed ultrasound-guided blocks utilized by the clinician. Recent findings With recent advances in both sonographic capability and access for anesthesia providers, many peripheral-nerve blocks have become quite amenable to being placed with ultrasound guidance. In addition, the subspecialty of ultrasound-guided regional anesthesia is being further pioneered via both anatomical and pharmacological studies. Summary With ultrasound guidance, the regional anesthesiologist has yet another tool to enhance both the accuracy and success of peripheral-nerve blockade. This article serves to display the most clinically relevant nerve blocks utilized in the perioperative setting. It is meant to be used as a clinical starting point for the development of regional anesthesia skills.

Single-dose extended-release epidural morphine for pain following hip arthroplasty.

This open-label, serial-cohort pilot study evaluated DepoDur™, a new, single-dose, extended-release epidural morphine (EREM) for pain control after hip arthroplasty. Single-dose EREM (10-30 mg) or a single dose of standard morphine sulfate (MS) (5 mg) was administered before surgery and spinal anesthesia. Among the 39 patients enrolled, total 48-hour supplemental fentanyl use was lower (P = 0.011 overall treatment) and median time to first postoperative fentanyl use was three- to six-fold longer (P < 0.001 overall treatment), among 10-, 20-, and 30-mg single-dose EREM patients versus MS patients. EREM patients reported higher levels of satisfaction with pain intensity scores comparable to MS patients. Safety results were similar between groups. Single-dose EREM was generally safe and effective for treating postoperative pain and reduced the need for supplemental analgesia.

A study of anesthetic drug utilization in different age groups

STUDY OBJECTIVE To determine anesthetic drug utilization in different age groups. DESIGN Retrospective, automated, intraoperative database study. SETTING Tertiary care medical center. MEASUREMENTS 30,842 noncardiac general anesthesia case records between January 1991 and July 1997 were studied. We investigated the effect of age on anesthetic requirements for fentanyl (F), midazolam (M), thiopental sodium (T), propofol (P), isoflurane (I), and nitrous oxide (N). Because drugs are not given in isolation we looked at the most common drug combinations, IFNTM, IFNPM, INFT, and PFNM. Regression analyses on log-transformed drug dosages were used to test the significance of age on individual requirements. RESULTS In each of the above anesthetic drug combinations, reduced doses of fentanyl, propofol, midazolam, thiopental, and isoflurane were used with increasing age. Fentanyl, propofol, thiopental, and isoflurane showed a 10%, 8%, 6%, and 4% reduction in dose per decade of age, respectively, from age of maximum dose to age 80 years. CONCLUSIONS In clinical practice, increasing age results in decreased anesthetic drug administration. The mechanism of this observation needs to be determined.