The effect of chlorzoxazone on acute pain after spine surgery. A randomized, blinded trial.

BACKGROUND: Chlorzoxazone is a muscle relaxant administered for musculoskeletal pain, and as an analgesic adjunct for post-operative pain. Chlorzoxazone for low back pain is currently not advised due to the lack of placebo-controlled trials. We explored the effect of chlorzoxazone on acute pain after spine surgery. METHODS: One hundred and ten patients were randomly assigned to 500 mg oral chlorzoxazone or placebo in this blinded study of patients having spine surgery under general anaesthesia. In the 4 h trial period analgesia consisted of IV patient-controlled analgesia (morphine bolus 2.5 mg). Primary outcome was pain during mobilization (visual analogue scale) 2 h after the intervention. Secondary outcomes were pain at rest, opioid consumption, nausea, vomiting, sedation and dizziness. RESULTS: For pain during mobilization 2 h after intervention, there was no significant difference between groups: 51 (21) vs. 54 (25) mm in the chlorzoxazone and placebo groups, respectively, mean difference 3 mm (95% CI -8 to 10), P = 0.59. For pain during mobilization and at rest (wAUC 1-4 h), there were no significant differences between groups. There was no significant difference in total IV morphine use 0-4 h: median 10 (7-21) vs. 13 (5-19) mg in the chlorzoxazone and placebo groups, respectively, P = 0.82. We found no significant difference in adverse effects. CONCLUSION: No analgesic effect of single-dose chlorzoxazone was demonstrated in patients with acute pain after spine surgery. Based on these findings, chlorzoxazone cannot be recommended for immediate treatment of acute pain after such procedures.

The efficacy of adductor canal blockade after minor arthroscopic knee surgery--a randomised controlled trial.

BACKGROUND: Adductor canal blockade (ACB) has been demonstrated to be effective in the treatment of post-operative pain after major knee surgery. We hypothesised that the ACB would reduce pain and analgesic requirements after minor arthroscopic knee surgery. METHODS: Seventy-two patients scheduled for minor knee surgery were enrolled in this placebo-controlled, blinded trial. The patients were randomised to receive an ACB with either 30 ml ropivacaine 7.5 mg/ml (n = 36) or saline (n = 35) in addition to a basic analgesic regimen with paracetamol and ibuprofen. Primary outcome measure was pain during standing at 2 h after surgery. Secondary outcomes were pain at rest, while standing and after a 5-m walk; opioid consumption and opioid-related side effects 0-24 h after surgery. RESULTS: Pain scores {median [interquartile range (IQR)]}, regarding primary outcome were 15 (0-26) mm in the ropivacaine vs. 17 (5-28) mm in the control group, 95% confidence interval (CI) (-10 to 4) mm, P = 0.41. Ketobemidone consumption 0-2 h post-operatively [median (IQR)] was lower in the ropivacaine vs. the control group: 0.0 (0.0-2.5) mg vs. 2.5 (0.0-5.0) mg, 95% CI: -2.5 to 0 mg, P = 0.01. No differences were observed for any other outcome. CONCLUSION: No significant analgesic effect of the ACB could be detected after minor arthroscopic knee surgery with a basic analgesic regimen with acetaminophen and ibuprofen, except from a minor reduction in immediate requirements for supplemental opioids. Clinicaltrials.gov Identifier: NCT01254825.

Effects of adductor-canal-blockade on pain and ambulation after total knee arthroplasty: a randomized study.

BACKGROUND: Total knee arthroplasty (TKA) is associated with intense post-operative pain. Besides providing optimal analgesia, reduction in side effects and enhanced mobilization are important in this elderly population. The adductor-canal-blockade is theoretically an almost pure sensory blockade. We hypothesized that the adductor-canal-blockade may reduce morphine consumption (primary endpoint), improve pain relief, enhance early ambulation ability, and reduce side effects (secondary endpoints) after TKA compared with placebo. METHODS: Patients aged 50-85 years scheduled for TKA were included in this parallel double-blind, placebo-controlled randomized trial. The patients were allocated to receive a continuous adductor-canal-blockade with intermittent boluses via a catheter with either ropivacaine 0.75% (n = 34) or placebo (n = 37) (http://www.clinicaltrials.gov Identifier: NCT01104883). RESULTS: Seventy-five patients were randomized in a 1 : 1 ratio and 71 patients were analyzed. Morphine consumption from 0 to 24 h was significantly reduced in the ropivacaine group compared with the placebo group (40 ± 21 vs. 56 ± 26 mg, P = 0.006). Pain was significantly reduced in the ropivacaine group during 45 degrees flexion of the knee (P = 0.01), but not at rest (P = 0.06). Patients in the ropivacaine group performed the ambulation test, the Timed-Up-and-Go (TUG) test, at 24 h significantly faster than patients in the placebo group (36 ± 17 vs. 50 ± 29 s, P = 0.03). CONCLUSION: The adductor-canal-blockade significantly reduced morphine consumption and pain during 45 degrees flexion of the knee compared with placebo. In addition, the adductor-canal-blockade significantly enhanced ambulation ability assessed by the TUG test.

Pregabalin and dexamethasone in combination with paracetamol for postoperative pain control after abdominal hysterectomy. A randomized clinical trial.

BACKGROUND: Multimodal analgesia may be important for optimal postoperative pain treatment and facilitation of early mobilization and recovery. We investigated the analgesic effect of pregabalin and dexamethasone in combination with paracetamol after abdominal hysterectomy. METHODS: One hundred and sixteen patients were randomly assigned to either group A (paracetamol+placebo x 2), group B (paracetamol+pregabalin+placebo) or group C (paracetamol+pregabalin+dexamethasone). According to randomization and preoperatively, patients received paracetamol 1000 mg, pregabalin 300 mg, dexamethasone 8 mg or placebo. General anaesthesia was performed. Postoperative pain treatment was paracetamol 1000 mg x 4 and patient-controlled intravenous morphine, 2.5 mg bolus. Nausea was treated with ondansetron. Morphine consumption, pain score (visual analogue scale) at rest and during mobilization, nausea, sedation, dizziness, number of vomits and consumption of ondansetron were recorded 2, 4 and 24 h after the operation. P<0.05 was considered statistically significant. RESULTS: The 24-h morphine consumption and pain score, both at rest and during mobilization, were not significantly different between treatment groups. The mean nausea score (P=0.002) was reduced in group C vs. A. The number of vomits was significantly reduced in both group B (P=0.041) and C (P=0.001) vs. A. Consumption of ondansetron was reduced in group C vs. A and B (P<0.001). Other side effects were not different between groups. CONCLUSION: Combinations of paracetamol and pregabalin, or paracetamol, pregabalin and dexamethasone did not reduce morphine consumption and pain score compared with paracetamol alone for patients undergoing abdominal hysterectomy. Dexamethasone reduced nausea, vomiting and use of ondansetron.

Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial.

BACKGROUND: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. METHODS: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. RESULTS: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53-88) mg to 43 (28-60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. CONCLUSION: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups.

Effect of epidural bupivacaine vs combined epidural bupivacaine and morphine on gastrointestinal function and pain after major gynaecological surgery.

In a double-blind study, we investigated the effects of postoperative epidural local anaesthetic, with or without addition of epidural morphine, on postoperative pain and gastrointestinal function in patients scheduled for radical hysterectomy and pelvic lymphadenectomy. Forty patients were randomized into two study groups: 48-h postoperative epidural 0.2% bupivacaine 8 ml h(-1) (bupi group) or 48-h postoperative epidural 0.2% bupivacaine/morphine 50 microg at 4 ml h(-1) (bupi/morph group). Patients were observed for at least 96 h after surgery. No differences in pain at rest, during cough or mobilization were observed. Patients in the bupi group requested a significant greater amount of supplementary analgesics, but times to first flatus and defaecation were reduced compared with patients in the bupi/morph group. Itching was a significant problem in patients in the bupi/morph group. No differences in postoperative nausea and vomiting, mobilization or time to discharge from hospital were observed between groups. The addition of morphine to postoperative epidural bupivacaine has only limited effect on pain relief and increases time to normalization of gastrointestinal function.

Effect of peri- and postoperative epidural anaesthesia on pain and gastrointestinal function after abdominal hysterectomy.

In a double blind study we have investigated the effects of epidural local anaesthesia (LA), when added to general anaesthesia (GA) and postoperative paracetamol and NSAID, on postoperative pain and gastrointestinal function in patients undergoing open hysterectomy. Sixty patients were randomized into three study groups: GA, and postoperative paracetamol and NSAID (GA, n=20); GA, paracetamol, NSAID, intraoperative epidural lidocaine and 24-h postoperative epidural saline (Saline, n=20); or GA, paracetamol, NSAID, intraoperative epidural lidocaine and 24-h postoperative epidural bupivacaine (Bupi, n=20). Patients were observed for 72 h postoperatively. Pain at rest, during cough, and mobilization, request for supplementary morphine, and time to first postoperative flatus, was reduced in patients receiving 24-h postoperative epidural anaesthesia, compared with the two other groups. However, these effects of epidural LA, were not sustained beyond the period of infusion, and no differences in PONV, time to first postoperative defecation, mobilization or time to discharge from hospital were observed between groups. A 24 h postoperative epidural infusion with bupivacaine, when added to postoperative paracetamol and NSAID, reduces pain and opioid requirements, but has only limited effects on gastrointestinal function and patient recovery.

Effect of continuous epidural 0.2% ropivacaine vs 0.2% bupivacaine on postoperative pain, motor block and gastrointestinal function after abdominal hysterectomy.

We have investigated the effect of 24-h postoperative continuous epidural infusion of 0.2% ropivacaine or 0.2% bupivacaine 8 ml h-1 on pain, request for supplementary analgesics, motor block and gastrointestinal function, in a double-blind, randomized study in 60 patients undergoing open hysterectomy. There were no significant differences between groups in pain, number of patients requesting supplementary analgesics, motor block, ability to walk or time to first flatus or stool. In the subgroup of patients who received supplementary analgesics, patients in the ropivacaine group received significantly more ketorolac than patients in the bupivacaine group. Time to discharge from hospital was similar with ropivacaine and bupivacaine.

Immunosuppressive effects induced by the polysaccharide moiety of some bacterial lipopolysaccharides.

The immunomodulatory properties of several lipopolysaccharides (LPS) derived from clinical isolates of Pseudomonas aeruginosa, Branhamella catarrhalis, and Bordetella pertussis were evaluated for their capacity to influence the magnitude of the antibody response to type III pneumococcal polysaccharide (SSS-III), which is known to be regulated by suppressor and amplifier T cells (Ts and Ta, respectively). The administration of LPS, two days after immunization resulted in a significant increase in the antibody response. Such enhancement may be due mainly to the ability of the lipid A moiety of LPS to abolish the negative effects of activated Ts, thereby enabling Ta function to be more fully expressed; however, B cell mitogenicity of the LPS molecule also may be involved. By contrast, treatment with LPS at the time of immunization with SSS-III induces significant suppression of the SSS-III-specific antibody response; such suppression is not induced by LPS or lipid A derived from Escherichia coli and Salmonella minnesota, and is independent of the capacity of LPS to activate B cells polyclonally, an activity generally attributed to the lipid A fraction of LPS. Studies conducted with the LPS of P. aeruginosa indicated that the suppression induced is T cell dependent and mediated by the polysaccharide (PS) fraction of LPS; it appears to be due-at least in part-to the capacity of PS to expand or increase the size of the precursor pool of Ts, activated in response to SSS-III. The significance of these findings to the pathogenesis of certain gram-negative infections is discussed.

Brief ischemia-reperfusion induces stunning of endothelium in canine coronary artery.

BACKGROUND: Brief ischemic episodes that induce stunning of the myocardium may also induce stunning of the coronary endothelium. To test this hypothesis, we examined both in vivo and in vitro responses of canine coronary arteries exposed to brief ischemia. METHODS AND RESULTS: Functional recovery of the endothelium was examined in vivo during reperfusion after 15 minutes of ischemia. Vasodilatory responses to acetylcholine were severely impaired during the first hour of reperfusion but gradually improved over a 90-minute period after ischemia. The vasoconstrictive response to U46619 was enhanced for the first 30 minutes of reperfusion and returned to normal within 60 minutes. In vitro vasomotor responses to potassium chloride, acetylcholine, bradykinin, and sodium nitroprusside were examined in isolated segments of canine coronary arteries preexposed in vivo to brief ischemia (10-30 minutes) and 20 minutes of reperfusion. The results showed enhanced contractile responses and blunted endothelium-dependent but not endothelium-independent vasodilatory responses of arterial rings subjected to 10 minutes of ischemia. Twenty and 30 minutes of ischemia completely impaired endothelium-dependent vasodilation. When reperfusion was extended to 120 minutes after 15 minutes of ischemia, vasodilatory responses to acetylcholine had recovered by almost 90%. Examination of endothelial integrity by transmission electron microscopy after 10-15 minutes of ischemia revealed no evidence of structural damage. Twenty and 30 minutes of ischemia induced cytoplasmic vacuolation, partial detachment of endothelium, and swelling of cytoplasmic organelles. CONCLUSIONS: These data support the hypothesis that brief ischemia-reperfusion induces stunning of endothelium in which endothelium-dependent vasodilatory function is impaired temporarily without morphological damage.

Comparison of thromboxane synthetase inhibitor and methylprednisolone effects on protamine responses in dogs.

Neutralization of heparin anticoagulation by protamine produces catastrophic hemodynamic reactions in some patients. Using a canine model, we tested effects of thromboxane synthetase inhibition (CGS-13080) and glucocorticoid pretreatment on the cardiorespiratory effects of protamine. In control dogs, protamine decreased mean arterial pressure and cardiac output and increased mean pulmonary artery pressure, systemic and pulmonary vascular resistances (SVR, PVR), and airway pressure. Both CGS-13080 and methylprednisolone ameliorated some effects of protamine. CGS-13080 infusion decreased mean pulmonary artery pressure, SVR, and airway pressure after protamine injection relative to controls. Cardiac output and PVR were unaffected by the drug, whereas the decrease in mean arterial pressure was prolonged. Plasma thromboxane A2 metabolite (TXB2) concentrations were lower and prostacyclin metabolite (6-keto PGF1 alpha) concentrations were higher compared with that of controls. These experiments support a role for TXA2 in the response to protamine. Methylprednisolone pretreatment produced larger cardiac output and lower airway pressure after protamine injection compared with controls. Mean arterial pressure was improved, but not significantly. Mean pulmonary artery pressure, SVR, and PVR were not different from that of controls; TXB2 and 6-keto PGF1 alpha were unaffected. The effects of methylprednisolone appear unrelated to arachidonic acid metabolism, as TXB2 and 6-keto PGF1 alpha levels were unaffected.

Comparative immunochemistry of lipopolysaccharides from Branhamella catarrhalis strains.

Lipopolysaccharides (LPS) were extracted and purified from the type strain and from a clinical isolate of Branhamella catarrhalis. Chemical analysis revealed the presence of glucose, galactose, and glucosamine in different molar proportions in the LPS from these two isolates, whereas there was no difference between the two isolates in the ratios of ketodeoxyoctonate, phosphate, and the fatty acids C12, 3-OH-C12, and 3-OH-C11 present. Heptose or 3-OH-C14 was not detectable in either preparation. LPS from both strains appeared semirough according to sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, presenting a core polysaccharide plus one repeating unit. Immunoblotting, passive hemolysis, and hemolysis inhibition assays using anti-LPS antibodies from immunized rabbits demonstrated cross-reactivity between the LPS preparations; however, antigenic dissimilarities were also found, suggesting that more than one serotype may exist. The lipid A isolated from the two LPS was serologically identical and exhibited cross-reactivity with lipid A of members of the family Enterobacteriaceae. The B. catarrhalis LPS were biologically active, causing lethality in D-galactosamine-sensitized C57/BL6 mice and inducing Limulus amoebocyte lysate gelation.

Does N-acetylcysteine increase the excretion of trace metals (calcium, magnesium, iron, zinc and copper) when given orally?

N-Acetylcysteine (NAC) is known to decrease the exacerbation rate in patients with chronic bronchitis. It has also been shown that NAC has both an oxygen-radical scavenger and a heavy-metal chelating effect in high intravenous doses. In a study lasting 5 weeks, 10 healthy volunteers were treated with NAC 200 mg t.d.s. for two weeks. The concentrations of trace metals (Ca, Mg, Fe, Zn & Cu) in plasma were measured weekly and daily in a morning spot urine during the investigation. No significant change in plasma concentration or excretion was found during the two weeks of treatment, implying that additional administration of trace metals is unnecessary for patients treated perorally with a therapeutic dose of NAC.

Preliminary study on treatment of septic shock patients with antilipopolysaccharide IgG from blood donors.

A novel intravenous therapy consisting of polyvalent IgG antibodies to lipopolysaccharide (LPS, endotoxin) obtained from screening of blood donors was used for treatment of patients with profound septic endotoxin shock. Investigation of the anti-LPS IgG pharmacokinetics in the 10 patients revealed time related changes in the plasma concentrations of anti-LPS IgG, endotoxin, tumour necrosis factor (TNF) and the clinical parameters. A decrease in serum concentrations of IgG and IgM antibodies to LPS was observed prior to the immunotherapy as well as in a clinical example of lethal septicemia without anti-LPS immunotherapy. Increasing serum concentrations of anti-LPS IgG during antibody infusion was followed by a decrease in the concentration of endotoxin and TNF. In survivors an IgM and IgG anti-LPS antibody response developed. Using clinical parameters and APACHE II clinical severity scores to measure the clinical condition, a beneficial effect was observed within 24 h corresponding to a decrease in the calculated expected mortality rate from more than 80% to about 50%. Five patients (55%) expired during the study. One patient died in the early septic shock phase. One patient expired due to superimposed hemorrhagic shock. Three immunosuppressed patients died 1-2 weeks after initial recovery, 1 with fungal sepsis and 2 patients due to pseudomonas infection.