Naoki Kotani

Intrathecal Methylprednisolone for Intractable Postherpetic Neuralgia

BACKGROUNDnThere is no effective treatment for intractable postherpetic neuralgia. Because there is evidence that postherpetic neuralgia has an inflammatory component, we assessed treatment with intrathecally administered methylprednisolone to reduce pain in patients with this disorder.nnnMETHODSnWe enrolled 277 patients who had had intractable postherpetic neuralgia for at least one year, 270 of whom were followed for two years. The patients were randomly assigned to receive intrathecal methylprednisolone and lidocaine (3 ml of 3 percent lidocaine with 60 mg of methylprednisolone acetate, 89 patients), lidocaine alone (3 ml of 3 percent lidocaine, 91 patients), or no treatment (90 patients) once per week for up to four weeks. Each weekly dose was injected into the lumbar intrathecal space. Pain was evaluated before randomization, at the end of the treatment period, and then four weeks, one year, and two years later. Samples of cerebrospinal fluid were obtained for measurement of interleukin-8 before and at the end of the treatment period.nnnRESULTSnThere was minimal change in the degree of pain in the lidocaine-only and control groups during and after the treatment period. In the methylprednisolone-lidocaine group, the intensity and area of pain decreased, and the use of the nonsteroidal antiinflammatory drug diclofenac declined by more than 70 percent four weeks after the end of treatment. No complications related to intrathecal methylprednisolone were observed. Before treatment, the concentrations of interleukin-8 in the cerebrospinal fluid were inversely related to the duration of neuralgia in all the patients (r=-0.49, P<0.001). In the patients who received methylprednisolone, interleukin-8 concentrations decreased by 50 percent, and this decrease correlated with the duration of neuralgia and with the extent of global pain relief (P<0.001 for both comparisons).nnnCONCLUSIONSnThe results of this trial indicate that the intrathecal administration of methylprednisolone is an effective treatment for postherpetic neuralgia.

Preoperative Intradermal Acupuncture Reduces Postoperative Pain, Nausea and Vomiting, Analgesic Requirement, and Sympathoadrenal Responses

Background In a controlled and double-blind study, the authors tested the hypothesis that preoperative insertion of intradermal needles at acupoints 2.5 cm from the spinal vertebrae (bladder meridian) provide satisfactory postoperative analgesia. Methods The authors enrolled patients scheduled for elective upper and lower abdominal surgery. Before anesthesia, patients undergoing each type of surgery were randomly assigned to one of two groups: acupuncture (n = 50 and n = 39 for upper and lower abdominal surgery, respectively) or control (n = 48 and n = 38 for upper and lower abdominal surgery, respectively). In the acupuncture group, intradermal needles were inserted to the left and right of bladder meridian 18–24 and 20–26 in upper and lower abdominal surgery before induction of anesthesia, respectively. Postoperative analgesia was maintained with epidural morphine and bolus doses of intravenous morphine. Consumption of intravenous morphine was recorded. Incisional pain at rest and during coughing and deep visceral pain were recorded during recovery and for 4 days thereafter on a four-point verbal rating scale. We also evaluated time-dependent changes in plasma concentrations of cortisol and catecholamines. Results Starting from the recovery room, intradermal acupuncture increased the fraction of patients with good pain relief as compared with the control (P < 0.05). Consumption of supplemental intravenous morphine was reduced 50%, and the incidence of postoperative nausea was reduced 20–30% in the acupuncture patients who had undergone either upper or lower abdominal surgery (P < 0.01). Plasma cortisol and epinephrine concentrations were reduced 30–50% in the acupuncture group during recovery and on the first postoperative day (P < 0.01). Conclusion Preoperative insertion of intradermal needles reduces postoperative pain, the analgesic requirement, and opioid-related side effects after both upper and lower abdominal surgery. Acupuncture analgesia also reduces the activation of the sympathoadrenal system that normally accompanies surgery.

Intraoperative modulation of alveolar macrophage function during isoflurane and propofol anesthesia.

Background Alveolar macrophages are a critical part of the defense against pulmonary infection. Thus the authors determined time‐dependent changes in alveolar macrophage functions in patients having surgery who were anesthetized with isoflurane or propofol. Methods Patients anesthetized with propofol (n = 30) or isoflurane (n = 30) during orthopedic surgery were studied. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, and 2, 4, and 6 h after induction anesthesia and at the end of surgery. The fraction of aggregated and nonviable macrophages was determined. Then phagocytosis was measured by ingestion of opsonized and unopsonized particles. Finally, microbicidal activity was determined as the ability of the macrophages to kill Listeria monocytogenes directly. Results Demographic and morphometric characteristics of the patients given propofol and isoflurane were similar, as were their levels of pulmonary function and hemodynamic responses. The fraction of alveolar macrophages ingesting opsonized and unopsonized particles, and the number of particles ingested, decreased significantly over time, with the decrease slightly but significantly greater during isoflurane anesthesia. Microbicidal function decreased progressively during anesthesia and surgery, with the decrease almost twice as great during isoflurane compared with propofol anesthesia. The fraction of aggregated macrophages and recovered neutrophils increased over time in the patients given each anesthetic. Conclusions Pulmonary immunologic function changed progressively during anesthesia and surgery. The data from this study suggest that pulmonary defenses are modulated by the type of anesthesia and by the duration of anesthesia and surgery.

Volatile anesthetics augment expression of proinflammatory cytokines in rat alveolar macrophages during mechanical ventilation

BACKGROUNDnPrevious studies indicate that anesthesia and surgery induce an inflammatory reaction in alveolar macro phages. However,they filed to independently evaluate the relative contributions of factors including mechanical ventilation, general anesthesia, and surgical stress. Therefore, the authors tested the hypothesis that inflammatory reactions at the cellular level in alveolar macrophages are induced within 2 h of inhalation of volatile anesthetics under mechanical ventilation.nnnMETHODSnAfter administration of pentobarbital, rats were allocated to the nonventilated control or spontaneous or mechanical ventilation (n = 15/group) for 2 h at a fraction of inspired oxygen (FI(O2)) of 0.21. In a separate series of experiments, rats were mechanically ventilated without volatile anesthesia, or during exposure to halothane, enflurane, isoflurane, or sevoflurane (n = 15/group). Pulmonary lavage was performed, and RNA was extracted from harvested cells. The mRNA for the proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, macrophage inflammatory protein-2 (MIP-2), interferon gamma (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha) were measured by semiquantitative reverse transcription-polymerase chain reaction using beta-actin as an internal standard. Pulmonary lavage concentrations of these cytokines were measured by enzyme-linked immunoassay.nnnRESULTSnThe lavage cell count and cytology were similar in each series of the experiment. Gene expression of MIP-2 and TNF-alpha was greater during mechanical than spontaneous ventilation and nonventilation control However, the concentrations of cytokines except MIP-2 and TNF-alpha were less than detection levels. During exposure to volatile anesthetics, gene expression for IL-1beta, MIP-2, IFN-gamma, and TNF-alpha all increased significantly compared with mechanical ventilation alone. Significant increases in lavage concentrations of MIP-2 and TNF-alpha were also observed.nnnCONCLUSIONSnGene expression of proinflammatory cytokines increase after inhalation of volatile anesthetics under mechanical ventilation. These data indicate that inhalation of volatile anesthetics under mechanical ventilation induces an inflammatory response at the transcriptional level within 2 h.

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

UNLABELLEDnBACKGROUND 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).nnnMETHODSnWe 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.nnnRESULTSnWe 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.nnnCONCLUSIONSnOur 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.

Expression of genes for proinflammatory cytokines in alveolar macrophages during propofol and isoflurane anesthesia.

UNLABELLEDnAnesthesia and surgery induce macrophage aggregation and neutrophil influx, responses that characterize an inflammatory reaction in the distal airway. We thus evaluated the time-dependent expression of genes for proinflammatory cytokines during propofol and isoflurane anesthesia. We studied patients anesthetized with propofol (n = 20) or isoflurane (n = 20). Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. Expression of interleukin-1beta (IL-1beta), IL-6, IL-8, interferon gamma, and tumor necrosis factor-alpha was measured by semiquantitative polymerase chain reaction using beta-actin as an internal standard. We observed two 10-fold increases in gene expression of all proinflammatory cytokines except IL-6. The increases in IL-8 and interferon gamma were 1.5-3 times greater during isoflurane than propofol anesthesia. Expression of the genes for IL-1beta and tumor necrosis factor-alpha was similar with each anesthetic. Our data thus indicate that the pulmonary inflammatory response accompanying anesthesia and surgery is accompanied by the expression of proinflammatory cytokines, and that this expression was in some cases greater during isoflurane than propofol anesthesia.nnnIMPLICATIONSnGene expression of proinflammatory cytokines in alveolar macrophages increased significantly over time. The increases were greater during isoflurane than propofol anesthesia, suggesting that inflammatory responses at transcriptional levels in alveolar macrophages are modulated by the type and duration of anesthesia.UNLABELLED: We randomized 76 parturients to a double-blinded trial to receive spinal anesthesia with either hyperbaric or plain bupivacaine 9 mg with fentanyl 20 microg for elective cesarean delivery. A combined spinal-epidural technique was used. The onset and duration of anesthesia (absence of pinprick sensation), analgesia (absence of sharp sensation to pinprick), and absence of cold sensation and motor block were measured until recovery from the motor block. No major differences were seen in onset or duration of anesthesia between the groups. Motor block, however, vanished faster when hyperbaric bupivacaine was used (P < 0.05). The level of anesthesia (no pinprick sensation) required for painless operation was at dermatome T5. At this time, the absence of cold sensation ranged from dermatome T1 to C3. The median time for the anesthesia to reach dermatome T5 was 10 min. Cervical spread of pinprick anesthesia was noted in six patients, and five needed supplementary analgesics during surgery (not significant between the groups). Maternal satisfaction was good. Nine milligrams of either plain or hyperbaric bupivacaine with fentanyl intrathecally provided similar onset, depth, and duration of sensory anesthesia for cesarean delivery with good maternal satisfaction. Motor block developed and diminished faster with the hyperbaric solution. IMPLICATIONS: Nine milligrams of either plain or hyperbaric bupivacaine with fentanyl intrathecally provided similar onset, depth, and duration of sensory anesthesia for cesarean delivery with good maternal satisfaction. Motor block developed and diminished faster with the hyperbaric solution.

Supplemental Intraoperative Oxygen Augments Antimicrobial and Proinflammatory Responses of Alveolar Macrophages

Background The first goal was to test the hypothesis that 100% inspired oxygen maintained for approximately 8 h intraoperatively is not associated with impaired pulmonary oxygenation. The authors also tested the hypothesis that intraoperative inhalation of 100% oxygen augments proinflammatory and antimicrobial responses of alveolar macrophages during anesthesia and surgery. Methods The authors studied patients administered 100% oxygen (n = 30) and 30% oxygen (n = 30) during propofol–fentanyl general anesthesia. Alveolar macrophages were harvested by bronchoalveolar lavage immediately, 2, 4, and 6 h after induction of anesthesia, and at the end of surgery.The authors measured “opsonized” and “unopsonized” phagocytosis and microbicidal activity. RNA was extracted from harvested cells and cDNA was synthesized. The expression of interleukin(IL)–1&bgr;, IL-6, IL-8, interferon-&ggr; (IFN-&ggr;) and tumor necrosis factor &agr; (TNF-&agr;) was measured by semiquantitative polymerase chain reaction. Results Gene expression of all proinflammatory cytokines except IL-6 increased fourfold to 20-fold over time in both groups. However, expression of TNF-&agr; and IL-8, IFN-&ggr;, and IL-6 and IL-1&bgr; was 2–20 times greater in patients administered 100% than in those administered 30% oxygen. Unopsonized and opsonized phagocytosis and microbicidal activity decreased progressively, with the decreases being nearly twice as great during inhalation of 30% oxygen versus 100% oxygen. Conclusion Inhalation of 100% oxygen improved intraoperative decreases in phagocytic and microbicidal activity possibly because expression of proinflammatory cytokines was augmented. These data therefore suggest that intraoperative inhalation of 100% oxygen augments antimicrobial and proinflammatory responses in alveolar macrophages during anesthesia and surgery.

Analgesic Effect of a Herbal Medicine for Treatment of Primary Dysmenorrhea - A Double-blind Study

We evaluated the analgesic effect of Toki-shakuyaku-san (TSS) in women who had a combination of deficiency, of Yin, cold, and stagnated blood syndromes, and were suffering from dysmenorrhea. A diagnostic scoring system was used for determination of these conditions. We treated patients with either TSS or placebo during 2 menstrual cycles with a double-blind technique, and we followed them for 2 additional cycles. A significant alleviation of dysmenorrhea was observed in patients treated with TSS as compared to those treated with placebo. Our results suggest that TSS is effective for treatment of dysmenorrhea in patients with the above-mentioned conditions.

Cardiopulmonary bypass produces greater pulmonary than systemic proinflammatory cytokines.

Cardiopulmonary bypass (CPB) impairs pulmonary endothelial injury in part by increasing expression of adhesion molecules that results in neutrophil influx. Although numerous proinflammatory cytokines up-regulate these responses, the extent to which systemic and pulmonary proinflammatory cytokines increase remains unknown. We therefore examined systemic and pulmonary gene expression and production of proinflammatory cytokines during CPB. Bronchoalveolar lavage and peripheral blood sampling were performed just after the induction of anesthesia and at the end of surgery in 80 patients undergoing CPB. RNA was extracted from harvested cells and cDNA was synthesized by reverse transcription. The expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-&agr; (TNF-&agr;) was measured by semiquantitative polymerase chain reaction using &bgr;-actin as an internal standard. We also measured these cytokines in cultured alveolar macrophages and plasma monocytes in standard medium alone, or in the presence of lipopolysaccharide. We found 2- to 20-fold increases in gene expression for these cytokines in both plasma and alveolar leukocytes at the end of surgery. However, the increases were 4–8 times greater in alveolar than plasma leukocytes. Alveolar macrophages obtained at the end of surgery produced 1.5–3 times more IL-6, IL-8, and TNF-&agr; than those obtained at the beginning (P < 0.0001). Although plasma monocytes produced more IL-8 at the end of surgery (P < 0.001), TNF-&agr; and IL-6 did not increase. The production of all cytokines was 1.5–3 times greater in alveolar macrophages obtained at the end of surgery than in plasma monocytes obtained simultaneously (P < 0.005). Our data thus suggest that CPB provokes a greater pulmonary than systemic inflammatory response. Implications Both gene expression and production of proinflammatory cytokines were greater in alveolar than plasma leukocytes after cardiopulmonary bypass. These results suggest that cardiopulmonary bypass provokes more serious pulmonary than systemic inflammatory responses.

Loss of alveolar macrophages during anesthesia and operation in humans

Pulmonary macrophages play an important role in the host defense against infection, and the importance of this role is probably enhanced when the upper airway defenses are circumvented by endotracheal intubation.Studies in animals suggest that exposure to volatile anesthetics compromises the viability and function of alveolar macrophages. We studied the effect of surgery and anesthesia on the alveolar macrophages of 41 human subjects undergoing lower abdominal procedures of varying lengths during nitrous oxide-isoflurane anesthesia. Alveolar macrophages were harvested from bronchoalveolar lavage fluid obtained before incision and compared to those recovered just before emergence from anesthesia. Macrophages were analyzed for aggregation and viability, assessed by the ability of viable cells to exclude trypan blue dye. Operations lasting 2 h or less led to little aggregation and had little effect on viability. However, there was a strong correlation between loss of macrophages and the duration of surgery and anesthesia. Aggregation increased and viability decreased as a function of procedure length. Studies are needed to determine whether prolonged surgery contributes to the incidence of postoperative pulmonary complications by disturbing the function and survival of alveolar macrophages in humans. (Anesth Analg 1995;81:1255-62)