That IL-6 is an interesting target in the study of pain is underscored by its biomolecular properties, its localization after experimental pain, and its modulating effect on pain after administration.
MP4OX (oxygenated polyethylene glycol-modified hemoglobin) is a novel oxygen therapeutic agent specifically developed to perfuse and oxygenate tissue at risk for ischemia and hypoxia. In this study, ...we investigated the ability of MP4OX to treat hypotensive episodes. In addition, the tolerability profile of MP4OX in a large surgical population was established.
Patients from 21 study sites in 5 countries, scheduled to undergo primary hip arthroplasty under spinal anesthesia, were randomized in a double-blind manner to receive MP4OX or hydroxyethyl starch (HES) solution (Voluven®; HES 130/0.4). Patients received the first 250-mL dose of investigational product when systolic blood pressure decreased to the predefined dosing trigger. A second 250-mL dose was given only if the systolic blood pressure decreased to the same trigger level after administration of the first dose. The primary efficacy outcome was total duration of all hypotensive episodes during surgery and the first 6 hours after skin closure.
Of the 474 patients randomized, 405 reached the dosing trigger and received at least 1 dose. The mean total duration of all hypotensive episodes was significantly shorter (P < 0.0001) in the MP4OX group (52.4 ± 71.50 minutes; range, 3-442 minutes) compared with the HES group (137.6 ± 120.21 minutes; range, 5-435 minutes). The overall incidence of adverse events (AEs) in the intent-to-treat population was similar between the MP4OX and HES groups (75.2% vs 73.4%; P = 0.733). Transient increases in laboratory values were reported in more patients in the MP4OX group versus HES controls for aspartate aminotransferase (13.4% vs 7.4%; P = 0.052), alanine aminotransferase (6.9% vs 4.9%; P = 0.409), lipase (9.7% vs 3.6%; P = 0.015), and troponin (8.1% vs 2.0%; P = 0.006). There was no significant difference in the incidence of serious AEs reported (6.4% in MP4OX group vs 3.0% in HES controls; P = 0.106). Certain AEs did occur more frequently in the MP4OX group, including nausea (23.8% vs 14.3%; P = 0.016), bradycardia (14.9% vs 5.9%; P = 0.003), hypertension (8.4% vs 2.5%; P = 0.009), and oliguria (5.9% vs 1.5%; P = 0.019). The composite morbidity and ischemia end points did not reveal any differences between the 2 treatment groups.
Administration of MP4OX achieved the end point of treating perioperative hypotension in patients undergoing primary hip arthroplasty under spinal anesthesia. The study was not powered to demonstrate clinical benefit based on the composite morbidity or ischemia outcomes. Although efficacy end points with sufficient power were met, MP4OX is not being proposed for use in routine surgery where the risk-benefit profile would not be favorable based on the safety profile demonstrated in this study.
NMDA receptors are involved in the modulation of neuropathic pain behavior and central sensitization. In vivo, this is mostly demonstrated by the use of specific antagonists such as MK801. Because ...studies evaluating the direct impact of spinal NMDA in neuropathic pain models are lacking, we performed a series of experiments to study the role of spinal NMDA injection on existing cold allodynia, as a measurement of neuropathic pain behavior in rodents. Intrathecal injection of NMDA resulted in an enhanced neuropathic pain behavior in CCI rats on a cold plate. The activity was present from a dose of 5 ng/rat onward and could selectively be reversed by intraperitoneal injections of doses of ≥ 0.01 mg/kg MK801. These results support the regulatory role of NMDA receptors in the hypersensitivity to cold observed in neuropathic pain behavior in rodents.
BACKGROUND:Less than 50% of patients experience sufficient pain relief with current drug therapy for neuropathic pain. Minocycline shows promising results in rodent models of neuropathic pain but was ...not studied in humans with regard to the treatment of neuropathic pain.
METHODS:In this randomized, double-blind, placebo-controlled clinical trial, patients with subacute lumbar radicular pain received placebo, amitriptyline 25 mg, or minocycline 100 mg once a day (n = 20 per group) for 14 days. Primary outcome measure was the pain intensity in the leg as measured by a numeric rating scale ranging from 0 to 10 on days 7 and 14. Secondary outcome measures were the reduction of neuropathic pain symptoms in the leg as determined with a neuropathic pain questionnaire, consumption of rescue medication, and adverse events on days 7 and 14.
RESULTS:Sixty patients were randomized and included in an intention-to-treat analysis. After 14 days, patients in the minocycline and amitriptyline groups reported a reduction of 1.47 (95% confidence interval, 0.16–2.83; P = 0.035) and 1.41 (95% confidence interval, 0.05–2.78; P = 0.043), respectively, in the numeric rating scale compared to the placebo group. No differences were seen in the neuropathic pain questionnaire values at any time point during treatment between the three groups. The rate of adverse events in the amitriptyline group was 10% versus none in the minocycline and placebo groups. No differences were noted in the consumption of rescue medication.
CONCLUSIONS:Although both groups differed from placebo, their effect size was small and therefore not likely to be clinically meaningful.
BACKGROUND:In recent literature, it has been suggested that deep neuromuscular block (NMB) improves surgical conditions during laparoscopy; however, the evidence supporting this statement is limited, ...and this was not investigated in laparoscopic bariatric surgery. Moreover, residual NMB could impair postoperative respiratory function. We tested the hypotheses that deep NMB could improve the quality of surgical conditions for laparoscopic bariatric surgery compared with moderate NMB and investigated whether deep NMB puts patients at risk for postoperative respiratory impairment compared with moderate NMB.
METHODS:Sixty patients were evenly randomized over a deep NMB group (rocuronium bolus and infusion maintaining a posttetanic count of 1–2) and a moderate NMB group (rocuronium bolus and top-ups maintaining a train-of-four count of 1–2). Anesthesia was induced and maintained with propofol and remifentanil. The primary outcome measures were the quality of surgical conditions assessed by a single surgeon using a 5-point rating scale (1 = extremely poor, 5 = optimal), the number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery. Secondary outcome measure was the postoperative pulmonary function assessed by peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity, and by the need for postoperative respiratory support. Data are presented as mean ± standard deviation with estimated treatment effect (ETEmean difference 95% confidence interval) for group comparisons.
RESULTS:There was no statistically significant difference in the surgeon’s rating regarding the quality of the surgical field between the deep and moderate NMB group (4.2 ± 1.0 vs 3.9 ± 1.1; P = .16, respectively; ETE0.4 −0.1, 0.9). There was no difference in the proportional rating of surgical conditions over the 5-point rating scale between both groups (P = .91). The number of intra-abdominal pressure increases >18 cmH2O and the duration of surgery were not statistically different between the deep and moderate NMB group (0.2 ± 0.9 vs 0.3 ± 1.0; P = .69; ETE−0.1 −0.5, 0.4 and 61.3 ± 15.1 minutes vs 70.6 ± 20.8 minutes; P = .07, ETE−9.3 −18.8, 0.1, respectively). All the pulmonary function tests were considerably impaired in both groups when compared with baseline (P < .001). There was no statistically significant difference in the decrease in peak expiratory flow, forced expiratory volume in 1 second, and forced vital capacity (expressed as % change from baseline) between the deep and the moderate NMB group.
CONCLUSIONS:Compared with a moderate NMB, there was insufficient evidence to conclude that deep NMB improves surgical conditions during laparoscopic bariatric surgery. Postoperative pulmonary function was substantially decreased after laparoscopic bariatric surgery independently of the NMB regime that was used. The study is limited by a small sample size.
Background and Aims
Persistent low back pain after initially successful surgery that is not attributed to structural deficits is called failed back surgery syndrome (FBSS). When conservative and ...minimal invasive therapy fail, the recommended treatment is spinal cord stimulation (SCS). Because epidural fibrosis can be a contributing factor in the majority of FBSS patients, lumbosacral epiduroscopic lysis of adhesions may be considered as a less invasive alternative treatment option. We hypothesized that the use of epiduroscopic lysis of adhesions could reduce the need for SCS.
Methods
A pilot study was performed in 35 consecutive patients with FBSS who underwent epiduroscopic lysis of adhesions. SCS was considered if epiduroscopic lysis of adhesions gave less than 50% global perceived effect (GPE) improvement after 15 months of follow‐up. The GPE was measured 1 week and 6 months after the procedure.
Results
Over a period of 69 months, 35 patients were included. After 15 months of follow‐up, 43% of patients required SCS. Eight of the 15 patients who reported no short‐term improvement needed SCS; those patients had severe epidural fibrosis. One week after epiduroscopic lysis of adhesions, 34%, 23%, and 43% of patients reported GPE improvement of > 50%, 20% to 50%, and < 20%, respectively. After 6 months, 5 patients were lost to follow‐up, and 30%, 17%, and 16% of patients reported improvement of > 50%, 20% to 50%, and < 20%, respectively.
Conclusions
In this pilot study we observed a reduced need for SCS when lumbosacral epiduroscopic lysis of adhesions was used for patients with FBSS and magnetic resonance imaging–proven adhesions. These observations justify the evaluation of both treatment options in a prospective observational trial.
We evaluated the efficacy of intraarticular sufentanil in the prevention of postoperative pain after day-case arthroscopic procedures. Sixty patients were randomly assigned to receive either ...intraarticular sufentanil, 5 or 10 μg, and saline IV, or intraarticular saline and sufentanil 5 μg IV (control). All study medication was administered in a double-blinded fashion. Postoperatively and the day after surgery, pain levels at rest and during movement (i.e., active flexion of the knee), measured by a visual analog scale, were significantly lower in the Sufentanil groups compared with the Control group. Moreover, intraarticular sufentanil significantly reduced the postoperative consumption of analgesics. The time until discharge from the postanesthesia care unit (assessed by the Aldrete score) was significantly shorter in the patients receiving sufentanil intraarticularly. There were no significant differences between the two Sufentanil groups either in the intensity of postoperative pain or in discharge times from the postanesthesia care unit. We conclude that intraarticular sufentanil in arthroscopic knee procedures is a simple, effective, safe and well-tolerated analgesic technique for outpatients undergoing arthroscopic procedures. Increasing the dose sufentanil from 5 to 10 μg intraarticularly offered no additional advantage. Intraarticular sufentanil (5–10 μg) administration improves postoperative management after day-case diagnostic arthroscopic knee procedures.
