An analysis of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid of pregnant women: the effect on labor pain.

It is still unclear which neurotransmitters are involved in labor pain. We measured the concentrations of excitatory amino acids, nitric oxide, and prostaglandin E2 in the cerebrospinal fluid (CSF) of pregnant women, particularly in those with labor pain. The patients included in the study consisted of women who underwent cesarean delivery either with labor pain (Labor Pain group, n = 40) or without labor pain (Nonlabor Pain group, n = 58). All patients received spinal anesthesia (intrathecal injection of 10-12 mg of bupivacaine) for the operation, and 2 mL of CSF was collected before bupivacaine injection. Concentrations of aspartate and glutamate (0.50 +/- 0.06 microM and 0.79 +/- 0.10 microM, respectively) were significantly larger in the Labor Pain group than in the Nonlabor Pain group (0.35 +/- 0.03 microM and 0.54 +/- 0.04 microM, P < 0.05). There were no significant differences in the concentrations of nitric oxide and prostaglandin E2 between the groups. A positive correlation was found between CSF concentrations of excitatory amino acids and labor pain. IMPLICATIONS: The excitatory amino acids, aspartate and glutamate, play a role in labor pain. N-methyl-D-aspartate receptor antagonists may be useful for labor pain and postlabor uterine contraction pain relief.     

Comparative therapeutic evaluation of intrathecal versus epidural methylprednisolone for long-term analgesia in patients with intractable postherpetic neuralgia.

BACKGROUND AND OBJECTIVES The goal of this study was to evaluate the analgesic effects of intrathecal versus epidural methylprednisolone acetate (MPA) in patients with intractable postherpetic neuralgia (PHN). METHODS: We studied 25 patients with a duration of PHN of more than 1 year. The patients were randomly allocated to one of two groups: an intrathecal group (n = 13) and an epidural group (n = 12). Sixty milligrams of MPA was administered either into the intrathecal or the epidural space four times at 1-week intervals depending on the treatment group. Continuous and lancinating pain and allodynia were evaluated by a physician unaware of group assignment with a 10-cm visual analogue scale before treatment, at the end of treatment, and 1 and 24 weeks after treatment. In addition, cerebrospinal fluid (CSF) was obtained for measurement of interleukin (IL)-1beta, -6, and -8 and tumor necrosis factor-alpha before and 1 week after treatment. RESULTS: We found marked alleviation of continuous and lancinating pain and allodynia in the intrathecal group (P < .001). The improvements were much greater in the intrathecal group than in the epidural group at all time points after the end of treatment (P < .005). IL-8 in the CSF decreased significantly in the intrathecal group as compared to the epidural group at the l-week time point (P < .01), whereas the other cytokines were undetectable. CONCLUSIONS: Our results suggest the effectiveness of intrathecal as compared to epidural MPA for relieving the pain and allodynia associated with PHN. Also, our findings, together with the decrease in IL-8, may indicate that intrathecal MPA improves analgesia by decreasing an ongoing inflammatory reaction in the CSF.     

Onset and offset of intrathecal morphine versus nalbuphine for postoperative pain relief after total hip replacement

BACKGROUND: We designed this study to compare the postoperative analgesic effects of intrathecal morphine and nalbuphine, the endpoints being onset and offset of action. METHODS: Geriatric patients scheduled for elective total hip replacement under continuous spinal anaesthesia were randomized to two double-blinded groups in the recovery room as soon as they experienced a pain score higher than 3 cm on the visual analogue scale (VAS, 0-10 cm). Either 160 microg morphine or 400 microg nalbuphine in 4 ml normal saline were administered intrathecally. Pain scores on VAS, rescue analgesia (diclofenac and morphine, not allowed during the first 60 min), and the adverse effects (respiratory depression, postoperative nausea and vomiting, itching) were recorded for 24 h after surgery. RESULTS: The study was stopped after inclusion of 2 x 12 patients due to slow onset of analgesia in the morphine patients. In the nalbuphine group, when compared to the morphine group, the time to a pain score <3 cm (8+/-6 vs. 31+/-32 min, P<0.001), the time to the lowest pain score (18+/-11 vs. 66+/-75 min, P<0.001) and the time to the first systemic analgesic intervention for a pain score >3 cm (218+/-256 vs. 1076+/-440 min, P<0.05) were significantly shorter. The analgesic requirements during the first 24 h were significantly lower in the morphine group (P<0.001). CONCLUSION: We conclude that after total hip replacement, administration of intrathecal nalbuphine resulted in a significantly faster onset of pain relief and shorter duration of analgesia than intrathecal morphine.     

Nitric oxide (NO) metabolism in the cerebrospinal fluid of patients with severe head injury. Inflammation as a possible cause of elevated no metabolites.

BACKGROUND: This article investigates nitric oxide (NO) metabolism following severe head injury (SHI). We wished to clarify the alterations of NO metabolism end products that is associated with SHI, and to delineate the role of inflammation in this process. METHODS: In a prospective study, we simultaneously measured the concentrations of NO metabolites and interleukin-8 (IL-8) in the ventricular cerebrospinal fluid (CSF) of 11 patients who had suffered SHI. The CSF concentrations of nitrite (NO(-)(2)) and nitrate (NO(-)(3)) combined, and of IL-8 were measured during the following four time periods post-trauma: 6 to 10, 20 to 28, 40 to 56, and 64 to 74 hours. Levels were measured using the corresponding kits. RESULTS: Compared to the ventricular CSF control values, all of our SHI patients had significantly elevated CSF levels of NO(-)(2) plus NO(-)(3) (NO(-)(2) + NO(-)(3)) and IL-8 during all periods tested. CSF NO(-)(2) + NO(-)(3) and IL-8 concentrations reached their maximums simultaneously at 20 to 28 hours following trauma (Spearman's rank correlation = 0.609, p < 0.05), and NO(-)(2) + NO(-)(3) levels were significantly higher than those measured at 6 to 10, 40 to 56, and 64 to 74 hours. [Nitrite-nitrate concentrations: 6-10 hours: 19.22 +/- 6.75, 20-28 hours: 25 +/- 6.2 micromol/l, 40-56 hours: 19.82 +/- 4.47, and 64-74 hours: 19.72 +/- 4.61 micromol/l, (p < 0.05). IL-8 concentrations: 6-10 hours: 3,232 +/- 2,976.2, 20-28 hours: 3,458.45 +/- 3,048 pg/mL, 40-56 hours: 2,616.41 +/- 2,539.21, 64-74 hours: 1,388.88 +/- 1,216.7 pg/mL, (p < 0.001).]. This simultaneous surge in NO(-)(2) + NO(-)(3) and IL-8 in the initial 24 hours post-traumatic indicated that inflammation secondary to SHI increased the rate of NO metabolism, resulting in higher levels of metabolites in the CSF. CONCLUSION: In patients with SHI, CSF concentrations of the dominant metabolites of NO are elevated in the first 3 days after trauma. A similar concurrent spike in the CSF level of IL-8, a marker of acute inflammatory response, can also be demonstrated. These data indicate that the predominant cause of the higher CSF NO(-)(2) + NO(-)(3) concentrations observed in SHI is most likely inflammation.     

Cytokines accumulated in acquired renal cysts in long-term hemodialysis patients

BACKGROUND: Cytokines play a pivotal role in growth, differentiation, and apoptosis. In this study, we measured cytokine content in the renal cyst fluid of patients with acquired cystic disease of the kidney (ACDK) in order to elucidate the possibility that cytokines are related to the development of ACDK. PATIENTS AND METHODS: All or some of 15 cytokines, IL-1a, -1b, -2, -4, -5, -6, -8, -10, IFN-alpha, -gamma, G-, M-, GM-CSF, TNF-alpha, and vascular endothelial growth factor (VEGF) were analyzed in cyst fluid and serum of 12 patients on hemodialysis (HD) including 8 with ACDK and 8 with normally functioning kidneys by sandwich enzyme-linked immunosorbent assay. RESULTS: Out of these cytokines, only IL-6, -8, M-CSF, and VEGF were detected in the cyst fluid of patients with ACDK. Moreover, IL-6, -8, and VEGF showed significantly higher concentrations in the cyst fluid than in the blood (194.9 +/- 90.9 vs. 0.0 +/- 0.0 pg/ml, 2,377. 5 +/- 602.9 vs. 0.0 +/- 0.0 pg/ml, 5,167.8 +/- 1,316.9 vs. 41.1 +/- 14.7 pg/ml, respectively), while M-CSF showed comparable concentrations in the cyst fluid with those in the blood (3,519.4 +/- 730.0 vs. 3,250.3 +/- 319.1 pg/ml, p = 0.69). Additionally, IL-6, -8, and VEGF accumulated more abundantly in the cyst fluid of patients with ACDK than in that of patients with other cystic nephropathies including ADPKD patients on HD (194.9 +/- 90.0 vs. 4.6 +/- 3.2 pg/ml, 2,377.5 +/- 602.9 vs. 76.8 +/- 46.5 pg/ml, 5,167.8 +/- 1,316.9 vs. 131.1 +/- 63.1 pg/ml, respectively). However, there was no significant correlation between the intracystic concentrations of these cytokines and the corresponding cyst diameters. CONCLUSION: These results showed that in ACDK patients a local environment exists in which production or accumulation of certain cytokines is selectively enhanced compared with patients with other cystic nephropathies. They imply that these cytokines are closely related to pathogenesis particular to ACDK.     

The antiinflammatory and analgesic effects of baicalin in carrageenan-evoked thermal hyperalgesia

We tested baicalin for its antiinflammatory and analgesic effects (and the mechanisms) in a rat model of carrageenan-evoked thermal hyperalgesia. Pre- or posttreatment with baicalin (10, 30, or 100 mg/kg intraperitoneally) caused a significant analgesic effect with a similar effect of dose-matched ibuprofen. Furthermore, baicalin dose-dependently attenuated tumor necrosis factor-alpha (from 3510 +/- 150 pg/mL to 2860 +/- 148 pg/mL to 1480 +/- 210 pg/mL), interleukin (IL)-1beta (from 3210 +/- 210 pg/mL to 2200 +/- 140 pg/mL to 750 +/- 95 pg/mL), and IL-6 (from 58.5 +/- 9.8 pg/mL to 38.5 +/- 9.0 to 21.0 +/- 8.1 ng/mL) formation but enhanced IL-10 (from 18.1 +/- 2.5 pg/mL to 36.1 +/- 5.5 pg/mL to 71.2 +/- 9.5 pg/mL) production in paw exudates at 4 h after carrageenan injection. Prostaglandin E(2) (PGE(2)) and nitrate formation in the carrageenan-injected paws were dose-dependently inhibited by baicalin (10-100 mg/kg intraperitoneally) (PGE(2): from 15.9 +/- 2.1 ng/mL to 12.1 +/- 1.6 ng/mL to 6.2 +/- 1.8 ng/mL; nitrate: from 39.8 +/- 4.8 microM to 27.5 +/- 3.0 microM to 17.2 +/- 1.6 microM) at 4 h but not at 1.5 h after carrageenan injection. Increased myeloperoxidase activity in carrageenan-injected paws was also dose-dependently reduced by baicalin. These findings suggest that the antiinflammatory and analgesic mechanisms of baicalin may be associated with the inhibition of critical inflammatory mediators, including nitric oxide, PGE(2), and proinflammatory cytokines, accompanied by an increase in IL-10 production, as well as neutrophil infiltration at sites of inflammation. IMPLICATIONS: Our results showed that baicalin possesses an analgesic effect in carrageenan-evoked thermal hyperalgesia. The possible mechanisms of action of baicalin may be associated with the inhibition of proinflammatory mediator overproduction, including cytokines, nitric oxide, and prostaglandin E(2), as well as neutrophil infiltration. This implies that baicalin may be a potential therapeutic analgesic for inflammatory pain.     

Analysis of interleukin-8, interleukin-10, and tumor necrosis factor-alpha in the cerebrospinal fluid of patients with cervical spondylotic myelopathy

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The expression of interleukin-8 (IL-8), IL-10, and tumor necrosis factor-alpha (TNF-alpha) were measured in the cerebrospinal fluid (CSF) of patients with cervical myelopathy. The purpose of this study was to examine whether the CSF levels of those 3 cytokines differ significantly among 3 groups of patients with different diseases. METHODS: IL-8, IL-10, and TNF-alpha levels were analyzed using enzyme-linked immune assay. CSF samples were collected from 3 groups of patients. The cervical spondylotic myelopathy (CSM) group consisted of 35 patients. The ossification of the posterior longitudinal ligament group [(OPLL) group] consisted of 7 patients, and the control group consisted of 12 patients. The concentration of IL-8 was 69.0+/-35.2 pg/mL in the CSM group, 82.1+/-46.7 pg/mL in the OPLL group, and 43.5+/-20.9 pg/mL in the control group. The concentration of IL-8 was significantly higher in the CSM and OPLL groups than in the control group (P<0.05). There was no significant difference between the CSM group and OPLL group. The concentration of IL-10 and TNF-alpha in all groups was below the sensitivity of the measurements. CONCLUSIONS: In this study, the concentration of IL-8 was high in CSM and OPLL patients. However, the concentration of IL-10 and TNF-alpha was below the sensitivity of the measurements.     

Intrathecal clonidine as a sole analgesic for pain relief after cesarean section.

In a small number of studies and isolated case reports, intrathecally administered clonidine has been reported to relieve intractable cancer pain and to prolong spinal anesthesia induced by various local anesthetics. A double-blind placebo-controlled clinical trial was carried out in order to evaluate the effect of intrathecal clonidine on pain following cesarean section. Twenty patients who underwent elective cesarean section received, 45 min after general anesthesia, either 150 micrograms (n = 10) clonidine or saline (control group, n = 10) intrathecally. Pain scores were lower in clonidine- than saline-treated patients from 20 to 120 min after intrathecal injection, as measured by a visual pain linear analog scale (P less than 0.05). Pain relief, in terms of the first supplemental analgesic request by patients, lasted 414 +/- 128 min after intrathecal clonidine and 181 +/- 169 min (mean +/- SD) (P less than 0.01) after saline. Clonidine decreased systolic, diastolic, and mean arterial pressures compared to baseline values (P less than 0.05), but heart rate and central venous pressure were unaffected (difference not significant). Maximal reduction of systolic arterial pressure was 15 +/- 9%, of diastolic arterial pressure 22 +/- 12%, and of mean arterial pressure 18 +/- 12%. Clonidine did not affect arterial hemoglobin oxygen saturation or PaCO2. Patients in the clonidine group were significantly more sedated (P less than 0.05) and more frequently reported a dry mouth (P less than 0.01) compared to the normal saline group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Expression of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in seminal plasma of fertile and infertile men

The involvement of cytokines and other immunoregulatory factors in male infertility is still unclear. In the present study we compared the levels of IL-12, IL-10, PGE2, sIL-2R and sIL-6R in the seminal plasma (SP) of fertile and infertile men. Four groups were included: fertile donors (FERT), infertile men with azoospermia (AZOO), and infertile men with either oligoterato-asthenoazoospermia (OTA), or OTA with genital infection (OTA-INF). Cytokines and cytokine-soluble receptors in semen were evaluated by specific ELISA commercial kits. The levels of IL-12, sIL-2R and sIL-6R were similar in SP of fertile and infertile men. The mean levels of IL-10 in the SP of FERT, OTA and AZOO were 5.6 +/- 0.9, 4 +/- 2.8 and 8 +/- 3.5 pg ml-1, respectively, and did not differ significantly. The mean level of IL-10 in SP from OTA-INF (0.9 +/- 0.5 pg ml-1) was significantly lower than that for FERT (5.6 +/- 1.9 pg ml-1; P = 0.02) and AZOO (8.2 +/- 3.4 pg ml-1; P = 0.05), but not significantly different from that for OTA (3.7 +/- 2.1 pg ml-1). The mean SP level of PGE2 was significantly lower in SP of OTA-INF than FERT (7.67 +/- 2.26 and 19.67 +/- 3.69 micrograms ml-1, respectively; P < 0.02). In conclusion, the seminal plasma from fertile and infertile men contained similar levels of IL-12, sIL-2R and sIL-6R. However, the levels of IL-10 were significantly lower in SP from OTA-INF compared to FERT and AZOO. Our results indicate that specific cytokines and their soluble receptors are involved in the male reproductive system.     

Small-dose intrathecal clonidine and isobaric bupivacaine for orthopedic surgery: a dose-response study

We examined the dose-response relationship of intrathecal clonidine at small doses (相似文献   

Improvement in postoperative pain relief by the addition of midazolam to an intrathecal injection of buprenorphine and bupivacaine

BACKGROUND AND OBJECTIVE: Intrathecal injections of the benzodiazepine midazolam have been reported to cause antinociception in animals and pain relief in human beings, including the potentiation of opioid analgesia. This study compared the efficacy of the addition of midazolam to a mixture of buprenorphine and bupivacaine used for spinal anaesthesia. METHODS: The study was prospective, randomized, and observer blinded. It involved 60 patients (30 per group), ASA I and II, age 20-40 yr, undergoing minor and intermediate lower abdominal surgery under spinal anaesthesia. Patients were randomized into two groups: the control group received a spinal injection of hyperbaric bupivacaine (15 mg) plus buprenorphine (0.15 mg) and the experimental group received a spinal injection of the same two drugs and doses but supplemented with intrathecal midazolam (2 mg). RESULTS: The duration of postoperative analgesia in the control group was 9.24 +/- 2.57 h (mean +/- SEM), and 21.33 +/- 12.69 h in the midazolam treated group (P < 0.001). Patients treated with intrathecal midazolam had better pain relief judged by visual analogue score on coughing (P = 0.0013) and a nursing mobility score (P < 0.0001). Adverse effects were minor and their incidence was similar in both groups. CONCLUSIONS: We conclude that intrathecal midazolam 2 mg improves the quality and duration of postoperative pain relief afforded by intrathecal buprenorphine and bupivacaine.     

Plasma concentrations of meperidine and normeperidine following continuous intrathecal meperidine in patients with neuropathic cancer pain

BACKGROUND: Intrathecal administration of meperidine, an opioid with local anesthetic activity, can induce analgesia in patients with intractable cancer pain. However, continuous intrathecal administration may result in the accumulation of normeperidine, responsible for central nervous system toxicity. METHODS: Ten patients with neuropathic cancer pain, not responding to conventional opioid therapy, were treated with continuous intrathecal administration of meperidine. In all patients, plasma concentrations of meperidine and normeperidine were measured the first days after the start of treatment. Visual analog scale scores were recorded to evaluate pain relief. Quality of life was assessed before and 3 weeks following the start of intrathecal treatment. RESULTS: In three patients the plasma concentrations of meperidine and normeperidine increased rapidly. In one patient the plasma normeperidine concentration was higher than the meperidine concentration. One patient demonstrated transient symptoms suggestive for central nervous system excitation. Three weeks following the start of treatment, seven patients were available for evaluation of their quality of life. Pain relief and overall quality of life improved during the intrathecal treatment. CONCLUSION: We conclude that continuous intrathecal administration of meperidine alone, or in combination with clonidine, can provide significant pain relief in patients with poor pain control despite pharmacological treatment. However, accumulation of meperidine and normeperidine resulting in central nervous system toxicity may occur during this treatment.     

Preadministration of flurbiprofen suppresses prostaglandin production and postoperative pain in orthopedic patients undergoing tourniquet inflation

STUDY OBJECTIVES: To evaluate the effect of preadministration of flurbiprofen on the plasma concentrations of prostaglandin E2 (PGE2) and postoperative pain. DESIGN: Prospective, randomized, controlled and double-blind study. SETTING: Inpatient surgery at Nagasaki Rosai Hospital. PATIENTS: 32 ASA physical status I to II patients scheduled for total knee arthroplasty or open anterior cruciate ligament reconstruction. INTERVENTIONS: Patients were randomly assigned to two groups. Five minutes before tourniquet inflation (350 mmHg), group A (n = 16) received placebo (intralipid, one mL . kg(-1)), and group B (n = 16) received flurbiprofen one mg . kg(-1) IV. Catheters were placed in the ipsilateral femoral vein for collection of local blood and in a cubital vein for sampling of systemic blood. MEASUREMENTS: Prostaglandin E2 (femoral vein and cubital vein) was measured before tourniquet inflation (T1), before tourniquet deflation (T2), and immediately after tourniquet deflation (T3). Postoperative analgesia was provided with intravenous buprenorphine, 0.1 mg, on patient demand. Pain (Visual Analog Scale) was assessed at 0.5, one, two, 4, 6, 12 and 24 hours after surgery. MAIN RESULTS: Visual Analog Scale and buprenorphine consumptions in group B were significantly lower than those in group A during the first 4 postoperative hours. In group A, PGE2 in femoral vein increased significantly at T2 (359 +/- 105 pg mL(-1), P < 0.0001), compared with T1 (211 +/- 61 pg mL(-1)) and returned to control values at T3 (252 +/- 77 pg mL(-1)), whereas PGE2 in the cubital vein showed no change. In group B, PGE2 in either the femoral vein or cubital vein showed no change throughout the time course. CONCLUSIONS: Preadministration of flurbiprofen suppresses the local production of PGE2 during tourniquet ischemia, resulting in reduced early postoperative pain in patients undergoing knee surgery.     

The efficacy of intrathecal morphine and clonidine in the treatment of pain after spinal cord injury

We performed a double-blinded, randomized, controlled trial in 15 patients to determine the efficacy of intrathecal morphine or clonidine, alone or combined, in the treatment of neuropathic pain after spinal cord injury. The combination of morphine and clonidine produced significantly more pain relief than placebo 4 h after administration; either morphine or clonidine alone did not produce as much pain relief. In addition, lumbar and cervical cerebrospinal fluid (CSF) concentrations, sampled at these levels at different times after administration were examined for a relationship between pain relief and CSF drug concentration. Lumbar CSF drug concentrations were initially several orders of magnitude larger than those in cervical CSF. After 1-2 h, the concentrations of morphine in cervical CSF markedly exceeded those of clonidine. The concentration of morphine in the cervical CSF and the degree of pain relief correlated significantly. We conclude that intrathecal administration of a mixture of clonidine and morphine is more effective than either drug administered alone and is related to the CSF-borne drug concentration above the level of spinal cord injury. If there is pathology that may restrict CSF flow, consideration should be given to intrathecal administration above the level of spinal cord damage to provide an adequate drug concentration in this region.     

Cerebrospinal norepinephrine concentrations and the duration of epidural analgesia

This study was performed to determine whether the addition of norepinephrine to local anaesthetics prolongs epidural analgesia in man. In addition, cerebrospinal fluid norepinephrine (NE) concentrations were measured. In the first part of the study, epidural catheters were inserted in 14 patients before herniotomy. Mepivacaine, 1.5 per cent (0.35 ml.kg-1), was administered and norepinephrine (5 micrograms.ml-1) was added in seven patients. The duration of anaesthesia was prolonged from 54 +/- 11 min to 83 +/- 12 min (P less than 0.05) and CSF NE concentrations increased from 68 +/- 12 pg.ml-1 to 336 +/- 85 pg.ml-1 in the NE group (P less than 0.01). In the second part, eight patients with herpetic neuralgia received epidural analgesia at the fourth to eighth thoracic interspace, using bupivacaine 0.25 per cent, with and without NE. The CSF NE concentrations in this group were greater than in the surgical patients before operation and increased from 254 +/- 58 to 406 +/- 58 pg.ml-1 30 min after administration of bupivacaine with NE. The duration of pain relief was prolonged with NE. These results suggest that adding NE to local anaesthetics prolongs epidural analgesia. Moreover, NE concentrations in surgical patients increased to levels similar to those found in patients suffering from herpetic analgesia. This suggests that the increase of CSF NE in chronic pain states has an antinociceptive effect.     

Impact of intramedullary instrumentation versus damage control for femoral fractures on immunoinflammatory parameters: prospective randomized analysis by the EPOFF Study Group

BACKGROUND: Damage control orthopedic surgery has recently been advocated for the management of femoral shaft fractures in severely injured patients because surgical procedures were found to represent a second-hit phenomenon regarding the operative burden. It has been attempted to determine the operative burden by means of proinflammatory cytokines. In this study in clinically stable patients with multiple injuries, the effects induced by different types of primary fracture stabilization on the systemic release of proinflammatory cytokines were evaluated. METHODS: This was a prospective, randomized, multicenter intervention study. Inclusion criteria were long bone shaft fracture of the lower extremity; age 18 to 65 years; Injury Severity Score > 16 or more than three extremity injuries (Abbreviated Injury Scale [AIS] score of 2 or more) in association with another injury (AIS score of 2 or more); and thoracic AIS score < 4. After informed consent, randomization for the treatment of the femoral shaft fracture was performed at admission. Groups were as follows: group I degrees FN (primary, < 24 hours) intramedullary nailing, and group DCO (DCO, I degrees ex.fix.) damage control orthopedic surgery and external fixation. In DCO patients, measurements were also performed at the time of conversion to the intramedullary procedure (DCO II degrees FN). Parameters included clinical parameters and complications (acute respiratory distress syndrome, multiple organ failure, sepsis). From serially sampled central venous blood, the perioperative concentrations of interleukin IL-1, IL-6, and IL-8 were determined.RESULTS Thirty-five patients were included (I degrees FN, n = 17; DCO, n = 18). In I degrees FN-patients, a perioperative increase of IL-6 levels was measured (preoperatively, 55 +/- 33 pg/dL; 24 hours postoperatively, +254 +/- 55 pg/dL; p = 0.03), which was not found in subgroup DCO I degrees Ex.fix.: preoperatively, 71 +/- 42 pg/dL; 24 hours postoperatively, 68 +/- 34 pg/dL; not significant [NS] or in group DCO II degrees FN: preoperatively, 36 +/- 21 pg/dL; 24 hours postoperatively, +39 +/- 25 pg/dL; NS. Likewise, in I degrees FN patients, a perioperative increase of IL-8 levels was measured only at the 7-hour time point (preoperatively, 35 +/- 29 pg/dL; 7 hours postoperatively, 95 +/- 23 pg/dL; p < 0.05), which was not found in group DCO I degrees Ex.fix.: preoperatively, 43 +/- 38 pg/dL; 24 hours postoperatively, 69 +/- 39 pg/dL; NS or in group DCO II degrees FN: preoperatively, 25 +/- 20 pg/dL; 24 hours postoperatively, 36 +/- 29 pg/dL; NS. There were no differences in the complication rate in terms of acute respiratory distress syndrome, sepsis, or multiple organ failure. CONCLUSION: In this prospective, randomized, multicenter study, a sustained inflammatory response was measured after primary (<24 hours) intramedullary femoral instrumentation, but not after initial external fixation or after secondary conversion to an intramedullary implant. These findings may become clinically relevant in patients at high risk of developing complications. It confirms previous studies in that damage control orthopedic surgery appears to minimize the additional surgical impact induced by acute stabilization of the femur.     

Analgesia for pelvic and perineal cancer pain by intrathecal steroid injection

BACKGROUND: Corticosteroids are used systemically in patients with advanced cancer to alleviate pain. Intrathecal administration of steroids is rarely performed but analgesic effects of intrathecal steroids have been reported in animal studies. We administered betamethasone intrathecally in three cancer patients with uncontrollable pain. CASE REPORT: Intrathecal injection of betamethasone (1-4 mg) with saline (total volume = 2 mL) was performed in three patients with advanced pelvic or perineal cancer, in whom pain could not be controlled in spite of various analgesic therapies. After obtaining the patient's informed consent for the procedure, betamethasone was administered intrathecally through the L4/5 intervertebral space. Intrathecal betamethasone produced rapid analgesia within 10 min and subsequent long-lasting analgesia for 5 days or more. Sleep, appetite and activity improved. No adverse effects were observed in any of the patients. CONCLUSIONS: Intrathecal injection of betamethasone may be a useful approach in some patients with intractable cancer pain.     

Seminal plasma cytokines and chemokines in prostate inflammation: interleukin 8 as a predictive biomarker in chronic prostatitis/chronic pelvic pain syndrome and benign prostatic hyperplasia

OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH.     

A comparison of intrathecal analgesia with fentanyl or sufentanil after total hip replacement

We designed this study to compare the postoperative analgesic effects of intrathecal fentanyl and sufentanil, the end points being onset, quality, and duration of action. A total of 42 geriatric patients, scheduled for elective total hip replacement under continuous spinal anesthesia, were randomized in two double-blinded groups as soon as they experienced a pain score higher than 3 of 10 on the visual analog scale in the recovery room. Either 7.5 microg sufentanil or 40 microg fentanyl in 2 mL normal saline were intrathecally administered. Pain scores, rescue analgesia (ketorolac and morphine), and adverse effects (respiratory depression, postoperative nausea and vomiting, and itching) were recorded for 24 h after surgery. In both groups, comparing sufentanil to fentanyl, the time to a pain score <3 (9 +/- 9 vs 11 +/- 8 min), the time to the lowest pain score (18 +/- 6 vs 20 +/- 15 min), and the time to the first systemic analgesic intervention for a pain score >3 (241 +/- 102 vs 214 +/- 120 min) were comparable as were the analgesic requirements during the first 24 h. We conclude that, after total hip replacement, both lipid soluble opioids produce excellent analgesia with comparable onset, duration of action, and low incidence of minor adverse effects. Implications: We compared the postoperative analgesic properties of 40 microg intrathecal fentanyl and 7.5 microg sufentanil after total hip replacement. Both opioids provided satisfactory analgesia, with comparable onset (11 +/- 8 vs 9 +/- 9 min) and duration of action (214 +/- 120 vs 241 +/- 102 min), as well as low incidence of minor side effects.     

Intrathecal sufentanil is more potent than intravenous for postoperative analgesia after total-hip replacement

BACKGROUND AND OBJECTIVES: In our clinical experience, sufentanil is more effective when administered intrathecally than intravenously. To test this hypothesis, we compared the analgesic characteristics of 7.5 microg of intrathecal or intravenous sufentanil for pain relief after total-hip replacement. METHODS: A randomized, double-blind study was conducted of 40 patients older than 75 years who experienced total-hip arthroplasty in which continuous spinal anesthesia was administered. In the recovery room, as soon as a pain score higher than 3 on a scale of 10 on a visual analog scale was reported, either 7.5 microg intrathecal or 7.5 microg intravenous sufentanil were given. If the pain score remained higher than 3 at 20 minutes after sufentanil administration,1.25 mg of "rescue" intrathecal bupivacaine were given. RESULTS: During the first 20 minutes after intrathecal or intravenous injection, a significantly faster relief of pain was observed for the intrathecal group from 2.5 until 20 minutes. Significantly, more patients needed rescue bupivacaine in the intravenous group (7 of 20 v 0 of 20, P < .008), whereas significantly more patients in the intrathecal group reached a pain score of 0 (20 of 20 v 9 of 20, P < .001). The time to the first analgesic intervention for a pain score greater than 3 was significantly longer in the intrathecal group (224 +/- 100 v 98 +/- 60 minutes, P < .001). Pruritus was observed only in 5 patients of the intrathecal group (P < .047), whereas peripheral oxygen saturation under 95% was observed only in 6 patients in the intravenous group (P < .045). CONCLUSIONS: After total-hip replacement, intrathecal route of sufentanil administration rapidly offers excellent analgesia of better quality and longer duration when compared with the intravenous route.