Clinical study on labor pain relief using the combined spinal-epidural analgesia and inhaling nitrous oxide. [Application of nitrous oxide in labor analgesia]. Nitrous oxide in early labor. Safety and analgesic efficacy assessed by a double-blind, placebo-controlled study. Patient-administered nitrous oxide/oxygen inhalation provides effective sedation and analgesia for colonoscopy. Methoxyflurane and nitrous oxide as obstetric analgesics. I. A comparison by continuous administration. Dose-response characteristics during long-term inhalation of nitric oxide in patients with severe acute respiratory distress syndrome: a prospective, randomized, controlled study. Entonox for labor pain: a randomized placebo controlled trial. Effect of ciclesonide and fluticasone on exhaled nitric oxide in patients with mild allergic asthma. The effect of low-dose inhaled fluticasone propionate on exhaled nitric oxide in asthmatic patients and comparison with oral zafirlukast. Inhaled nitric oxide in acute respiratory distress syndrome: a pilot randomized controlled study. Effects of inhaled nitric oxide in patients with acute respiratory distress syndrome: results of a randomized phase II trial. Inhaled Nitric Oxide in ARDS Study Group. Nitrous oxide (Entonox) inhalation and tolerance of transrectal ultrasound guided prostate biopsy: a double-blind randomized controlled study. Neonatal neurobehavioral effects of inhalation analgesia for vaginal delivery. Exhaled nitric oxide in bronchiectasis: the effects of inhaled corticosteroid therapy. A double-blind, randomized controlled trial on the use of a 50:50 mixture of nitrous oxide/oxygen in pain relief during suction evacuation for the first trimester pregnancy termination. Effect of inhaled nitric oxide on key mediators of the inflammatory response in patients with acute lung injury.
To study the pain relief effectiveness of the combined spinal-epidural analgesia (CSEA) and the inhalation of nitrous oxide, and the influences on the mothers and infants.
                The 300 cases of pregnant women were randomly divided into 3 groups: CSEA group, nitrous oxide group and control group. The nitrous oxide group was that pregnant women inhaled nitrous oxide premixed with oxygen (50%:50%), the pregnant women of the CSEA group were injected fentanyl and bupivacaine in the subarachnoid and epidural space, analgesic was not used in the control group. The degree of labor pain, duration of the labor, way of delivery, bleeding volume, rate of anoxia of newborn, blood gas analysis to maternal radius artery and fetal umbilical blood among 3 groups were observed.
                The effect for analgesia labor of the CSEA group was much better than that of the nitrous oxide group (P < 0.01). In the first stage of labor and total stage of labor, the CSEA group was shorter than the others (P < 0.05), but there was no difference between the nitrous oxide group and the control group (P > 0.05). In the second stage of labor, the 3 groups were alike to each other. The bleeding volume of caesarean section (373 +/- 77) ml in the nitrous oxide group was much more than the other 2 groups, there was no difference between the CSEA group (259 +/- 78) ml and the control group (239 +/- 89) ml. The rate of obstetric forceps of CSEA group was higher than the control group (P < 0.01), and the rate of caesarean section of the nitrous oxide group was much higher than the CSEA group. The blood gas analysis to maternal radius artery and fetal umbilical blood and the rate of anoxia of newborn of 3 groups revealed no significant difference.
                The effectiveness of the combined spinal-epidural analgesia CSEA for analgesia labor is confirmed and has rarely side-effect, and it can be the first choice, and the inhalation of nitrous oxide can safely provide effective labor analgesia, too. Labor analgesia with nitrous oxide was studied in 34 parturients, and another 50 women taking no drug as the control group. The analgesic effect was satisfactory. By Mulleetr's pain in labor score, 91.18% women had score of 0-1, and their respiratory and circulatory functions were not affected. During inhalational analgesia the parturients remained conscious. Uterine contraction, progress of labor and neonatal Apgar score were not interferred, and postpartum bleeding was not increased. There was no complications in the treatment group. This study suggests that nitrous oxide with enough oxygen inhalation is one of the good drug for obstetric analgesia, but its concentration must be strictly controlled. Intermittent self-administered nitrous oxide has long had widespread use as an analgesic in labor, but its efficacy has not been adequately established. Questions about its effect on maternal oxygenation between labor contractions also have been raised.
                Twenty-six women were recruited to participate in a randomized, double-blind, cross-over, placebo-controlled study to assess the effect of intermittent nitrous oxide inhalation on labor pain and maternal hemoglobin oxygen saturation (SPO2) during the first stage of labor. Visual analog scale pain scores for each of five consecutive labor contractions were measured after administration of either nitrous oxide or compressed air.
                Mean visual analog scale pain scores for five contractions were 5.1, 5.2, 5.7, 5.2, and 5.6 (nitrous oxide) and 4.9, 5.2, 6.1, 5.6, and 5.7 (compressed air). There were no statistically significant differences in pain when nitrous oxide as compared with compressed air was administered. Pain scores did not differ significantly over time as a function of inhaled substance (F = 0.41, P = 0.53). The mean lowest SPO2 observed between these contractions after self-administration of nitrous oxide and air were 97, 97, 97, 97, and 97% (nitrous oxide) and 97, 96, 96, 96, and 96% (compressed air). SPO2 was significantly higher after nitrous oxide administration (F = 8.8, P = 0.007).
                While intermittent self-administered 50% nitrous oxide in oxygen does not appear to predispose parturient women to hemoglobin oxygen desaturation, its analgesic effect has yet to be clearly demonstrated. In a double-blind, randomized, placebo-controlled study of patients undergoing colonoscopy, sedation with an inhaled mixture of nitrous oxide/oxygen was compared with conventional intravenous sedation (pethidine 50 mg, midazolam 2.5 mg). In the patients studied, no significant differences were noted in number of pain episodes, need for additional intravenous sedation, or patient pain scores between the group receiving the nitrous oxide/oxygen mixture (n = 30) and those managed with conventional benzodiazepine/opiate injection (n = 29). Both methods were significantly more effective than placebo (n = 30). Six patients in the benzodiazepine/opiate group had oxygen desaturation, whereas none did in the nitrous oxide/oxygen group. Duration of stay after the procedure was significantly shorter in the gas inhalation group than in those receiving conventional intravenous sedation. Except for patients with severe chronic obstructive pulmonary disease, nitrous oxide/oxygen inhalation is a safe and acceptable alternative method of sedation and analgesia during colonoscopy. Methoxyflurane and nitrous oxide have been compared as obstetric analgesics. The inhaled concentrations of these agents, given continuously, were adjusted by an anaesthetist to maintain each patient at the optimum state between reaction to pain and consciousness. Assessments were made continuously.Though the anaesthetist's assessment showed no difference between the mean results, a greater proportion of the methoxyflurane patients were "satisfactory" for 90-100% of the time than of the nitrous oxide patients, particularly in regard to objective pain relief. The midwives' opinion of those who had "complete" pain relief supported this. Nausea was significantly less among methoxyflurane patients, and vomiting during labour occurred only in patients who had nitrous oxide. It is concluded that nitrous oxide and methoxyflurane given in a continuously adjusted concentration are almost equally effective as obstetric analgesics, though there are certain features which favour methoxyflurane. Inhaled nitric oxide (NO) improves systemic oxygenation (PaO2/FIO2) in adult patients with acute respiratory distress syndrome (ARDS). However, individual response varies, and previous trials demonstrated no outcome benefit. This prospective, randomized study in 40 ARDS patients analyzed dose-response (DR) characteristics during long-term inhaled NO. Patients were randomized for conventional therapy (control) or continuous treatment with 10 parts per million (ppm) inhaled NO until weaning was initiated. We measured DR curves of PaO2/FIO2 versus the inhaled NO dose at regular intervals. Before treatment (Day 0), peak improvement in PaO2/FIO2 was achieved at 10 ppm for both control and NO-treated patients. After 4 days, the DR curve of the NO-treated patients was left shifted with a peak response at 1 ppm. At higher doses (10 and 100 ppm), oxygenation deteriorated, and the response to inhaled NO disappeared in several patients. This effect was not observed in the control group. There was no effect of inhaled NO on duration of mechanical ventilation or stay at the intensive care unit. In conclusion, long-term inhaled NO with constant doses of 10 ppm leads to enhanced sensitivity after several days and does do not allow reduction of ventilation parameters. Hence, previous trials on therapy with inhaled NO in ARDS should be carefully interpreted, as they used constant NO concentrations, which may have become overdoses leading to deterioration of oxygenation after several days. This study aims to investigate the effectiveness of nitrous oxide on pain of labor contractions and on maternal SaO2. The patients were randomized to receive either a pre-prepared mixture of 50% nitrous oxide and oxygen or 50% oxygen by a coin. Study drugs started as early as the onset of pain with each contraction. The patient herself administered gases via a facemask connected to the uni-directional valve which enables the patients to breathe fresh gas in each inspiration. The gas administration was continued to the end of contraction pain at which the patient breathed the room air. Variables such as SaO2, blood pressure, pain and side effects were recorded. 534 ASA I and II parturients, aged from 16 to 35 years, scheduled for elective labor from September 2004 to 2006 were evaluated. Four patients were lost from the study. The mean age of patients was 25.5+/-4.3 years. During the first three measurements, the SaO2 was significantly higher in control group. In addition, the mean arterial pressure was comparable between groups except two first measurements in which the control group was higher. All the Visual Analogue Scale (VAS) values were significantly lower in nitrous oxide group. There were no significant differences in 1st and 5th min apgar scores between groups. All of the side effects were significantly higher among patients in nitrous oxide. In conclusion, our data indicate that using nitrous oxide 50% provides significant pain relief. Nonetheless, it is associated with few side effects, nitrous oxide can be quickly implemented during advanced painful labor. Ciclesonide is a novel, lung-activated, inhaled corticosteroid with once-daily efficacy and potent anti-inflammatory activity. The aim of the study was to compare the effect of ciclesonide and fluticasone propionate on exhaled nitric oxide (FENO), pulmonary function, and other parameters used in clinical evaluation of patients with mild allergic asthma. The study indicates that ciclesonide (in a daily dose of either 80 or 160 microg) induces both a faster and stronger decrease of FENO in comparison with fluticasone (100 microg twice daily). In both groups of patients treated with ciclesonide, the highest decrease in FENO levels was observed after 2 weeks of treatment. In the group of patients treated with fluticasone, this maximum effect was not observed till 8 weeks. An improvement in spirometric indices was observed in all groups studied. Statistical differences between the groups were not found; however, there was a trend toward higher increase in the group receiving 160 microg of ciclesonide. In all groups studied we observed clinical improvement (asthmatic symptoms and consumption of rescue medication were reduced), but there were no significant differences between these groups. Our results indicate that ciclesonide, compared with fluticasone, has stronger anti-inflammatory activity in patients with mild allergic asthma. Exhaled nitric oxide (ENO) is a noninvasive marker of ongoing inflammation in asthmatic patients. Comparison between inhaled and oral anti-inflammatory medications in reduction of ENO in asthmatic patients has not been performed.
                We measured changes in ENO, spirometry, need for rescue medication, quality of life (QOL), and diary scores (DS) after inhaled and oral anti-inflammatory therapy in adults with moderate asthma.
                A randomized, double-blind, placebo-controlled, crossover design with 4-week washout periods was used. A plateau level of ENO, measured in parts per billion (ppb), was obtained by chemiluminescence with a Sievers 280NOA as per American Thoracic Society recommendations. Eighteen asthmatic adults (15 Hispanic, with a percentage predicted forced expiratory volume in 1 second (FEV1%) of 50% to 85%) on bronchodilators (beta2) only were studied. Subjects used fluticasone propionate (FP) metered-does inhaler (44 microg), two puffs twice daily, and matching placebo (PB) for 4 weeks. Eight of the asthmatic patients (7 Hispanic, FEV1% 50% to 85%) on bronchodilators only then received blinded zafirlukast (ZK) 20 mg and matching PB twice daily for 4 weeks.
                Low-dose inhaled FP resulted in significant improvements in ENO, spirometry, QOL, DS, and beta2 use. A significant difference in mean ENO was found (P < 0.01) before and after FP from 34+/-7 ppb to 13+/-3 ppb. A significant improvement was found (P < 0.05) with FEV1% from 75+/-3 to 85+/-3 with FP treatment. The other measured parameters, percentage predicted of peak expiratory flow rate, beta2 need, DS, and QOL measurements, were improved with low-dose FP treatment. No significant reduction was found in ENO with oral ZK for 4 weeks. After oral ZK washout and the second extension arm of placebo, ENO significantly increased back to 47+/-14 ppb (P < 0.05), but spirometry measures did not worsen. Significant improvements were found with DS and beta2 use with oral ZK therapy.
                These results reveal ENO is reduced with only low-dose inhaled FP in asthmatic patients not on anti-inflammatory medication. In the smaller extension study, ENO was reduced with FP and not with oral ZK treatment, and ENO levels increased back to near prestudy levels after ZK washout and the second extension arm of placebo. As a marker of inflammation, ENO levels reveal an improvement with anti-inflammatory medication and worsening when it is discontinued. This pilot randomized controlled clinical trial of patients with ARDS was implemented to study the impact of inhaled nitric oxide (inhNO) on lung function, morbidity, and mortality. Thirty patients with ARDS were randomly allocated to usual care or usual care plus inhNO. The optimal dose of inhNO was determined to be between 0.5 and 40 parts-per-million daily. All therapeutic interventions were standardized. ARDS resulted mainly from sepsis (25 of the 30). During the first 24 h, the hypoxia score increased greatly in patients treated with inhNO +70.4 mm Hg (+59%) versus +14.2 mm Hg (+9.3%) for the control group (p = 0.02), venous admixture decreased from 25.7 to 15.2% in the inhNO group, and from only 19.4 to 14.9% in the control group (p = 0.05). After the first day of therapy no further beneficial effect of inhNO was detected. Forty percent of the patients treated with inhNO were alive and weaned from mechanical ventilation within 30 d after randomization compared with 33.3% in the control group (p = 0.83). The 30-d mortality rate was similar in the two groups; most deaths (11 of 17) were due to multiple organ dysfunction syndrome. This study shows that inhNO, in this population, may improve gas exchange but does not affect mortality. To evaluate the safety and physiologic response of inhaled nitric oxide (NO) in patients with acute respiratory distress syndrome (ARDS). In addition, the effect of various doses of inhaled NO on clinical outcome parameters was assessed.
                Prospective, multicenter, randomized, double-blind, placebo-controlled study.
                Intensive care units of 30 academic, teaching, and community hospitals in the United States.
                Patients with ARDS, as defined by the American-European Consensus Conference, were enrolled into the study if the onset of disease was within 72 hrs of randomization.
                Patients were randomized to receive placebo (nitrogen gas) or inhaled NO at concentrations of 1.25, 5, 20, 40, or 80 ppm.
                Acute increases in PaO2, decreases in mean pulmonary arterial pressure, intensity of mechanical ventilation, and oxygenation index were examined. Clinical outcomes examined were the dose effects of inhaled NO on mortality, the number of days alive and off mechanical ventilation, and the number of days alive after meeting oxygenation criteria for extubation. A total of 177 patients were enrolled over a 14-month period. An acute response to treatment gas, defined as a PaO2 increase > or =20%, was seen in 60% of the patients receiving inhaled NO with no significant differences between dose groups. Twenty-four percent of placebo patients also had an acute response to treatment gas during the first 4 hrs. The initial increase in oxygenation translated into a reduction in the FIO2 over the first day and in the intensity of mechanical ventilation over the first 4 days of treatment, as measured by the oxygenation index. There were no differences among the pooled inhaled NO groups and placebo with respect to mortality rate, the number of days alive and off mechanical ventilation, or the number of days alive after meeting oxygenation criteria for extubation. However, patients receiving 5 ppm inhaled NO showed an improvement in these parameters. In this dose group, the percentage of patients alive and off mechanical ventilation at day 28 (a post hoc analysis) was higher (62% vs. 44%) than the placebo group. There was no apparent difference in the number or type of adverse events reported among those patients receiving inhaled NO compared with placebo. Four patients had methemoglobin concentrations >5%. The mean inspired nitrogen dioxide concentration in inhaled NO patients was 1.5 ppm.
                From this placebo-controlled study, inhaled NO appears to be well tolerated in the population of ARDS patients studied. With mechanical ventilation held constant, inhaled NO is associated with a significant improvement in oxygenation compared with placebo over the first 4 hrs of treatment. An improvement in oxygenation index was observed over the first 4 days. Larger phase III studies are needed to ascertain if these acute physiologic improvements can lead to altered clinical outcome. We performed a randomized, placebo controlled double-blind trial to evaluate the effectiveness of Entonox (BOC Gases, Manchester, United Kingdom), that is 50% nitrous oxide and oxygen, as analgesia during transrectal ultrasound guided prostate biopsy.
                Patients referred for transrectal ultrasound guided prostate biopsy for the first time as an outpatient procedure were recruited subject to exclusion criteria and randomized to breathe Entonox or air via similar breath activated devices. At the end of the procedure patients completed a visual pain analog scale. Patients who refused study participation also completed the visual analog pain scale to assess the placebo effect of receiving gas through a mask.
                A total of 110 patients were studied. Statistical analysis using 1-way analysis of variance showed a highly significant difference in pain perception among the 3 groups (F [2,107] = 73.348, p <0.001). This significant decrease in pain was noted in the Entonox versus air and Entonox versus placebo groups. There was no significant difference in the air and placebo groups. Seven of the 51 patients receiving Entonox complained of feeling drowsy during the procedure, which resolved at completion of the procedure. In this group 49 patients would undergo this procedure again if needed. In 2 of the 45 patients in the group receiving air the procedure was abandoned due to pain, while another 19 would prefer more analgesia and 2 would prefer general anesthesia if the procedure was to be repeated.
                Our study shows that Entonox is a safe, rapidly acting and effective form of analgesia for the pain of prostate biopsy. We believe that it should be the analgesia of choice for this procedure. The authors studied the neonatal neurobehavioral effects of nitrous oxide:oxygen and enflurane:oxygen inhalation analgesia for vaginal delivery. Parturients were assigned randomly to receive no inhalation agent (Group 1, n = 21); enflurane, 0.3 to 0.8 per cent, and oxygen (Group 2, n = 22); or nitrous oxide, 30 to 50 per cent, and oxygen (Group 3, n = 18). Infants were tested at 15 min, 2 h, and 24 h of age using the Neurologic and Adaptive Capacity Score (NACS); and at 2 and 24 h using the Early Neonatal Neurobehavioral Scale (ENNS). No significant differences in neurobehavioral status occurred. For all groups, scores tended to be lowest at two hours of age. We conclude that neither enflurane nor nitrous oxide analgesia adversely affects neonatal neurobehavioral status at 15 min, 2 h, or 24 h of age. While exhaled nitric oxide (eNO) levels are reduced by inhaled corticosteroid therapy in asthma, such treatment effect is unclear in bronchiectasis.
                Stable non-smoking bronchiectasis patients were randomised to receive either fluticasone (1 mg/daily) or identical placebo via the Accuhaler device.
                Sixty non-smoking patients (38 women; mean age 56.4 +/- 12.7 years) were recruited. Of these, half received inhaled fluticasone and half placebo therapy. eNO was measured using a chemiluminescence analyser at 0, 4, 12, 24, 36 and 52 weeks. There was no significant difference in eNO levels between fluticasone and placebo patients over the study period. There was no correlation between baseline eNO with age, FEV1, FVC, 24 h sputum volume or number of bronchiectatic segments. Patients with Pseudomonas aeruginosa (PA) infection, but not their counterparts, displayed a correlation between 0- and 52-week eNO levels. PA infection was associated with significantly lower eNO levels among the patients.
                Inhaled fluticasone therapy, despite being an effective anti-inflammatory agent, has no significant effect on eNO production, either at individual time points or over the entire 52-week profile, in bronchiectasis. It appears that eNO might not reflect the extent of airway inflammation in bronchiectasis. This prospective study assessed the role of a 50:50 mixture of nitrous oxide (N2O) and oxygen for pain relief during the termination of first trimester pregnancies by suction evacuation under conscious sedation.
                Ninety women undergoing suction evacuation up to 12 weeks of gestation were randomized by a computer-generated randomization list and allocated using sealed envelopes to receive the N2O/O2 mixture or air during the operation. Pain scores during and after suction evacuation, post-operative side effects and satisfaction level were compared.
                No statistically significant differences in pain scores, post-operative side effects and satisfaction levels were found between the two groups.
                N2O/O2 did not reduce the pain level during suction evacuation for the first trimester pregnancy termination under conscious sedation. Inhaled nitric oxide is used to treat hypoxia associated with acute lung injury. Endogenous nitric oxide regulates inflammatory responses, but the effect of inhaled nitric oxide therapy is unknown. We hypothesized that inhaled nitric oxide may alter inflammatory responses and endogenous nitric oxide synthase activity.
                A randomized, prospective interventional study.
                A university hospital's general intensive care unit.
                Thirty-two patients with acute lung injury.
                Patients who responded to test doses of nitric oxide were randomized to ventilator therapy with and without inhaled nitric oxide. The inhaled concentration of nitric oxide was determined by dose titration at 0, 2, 10, and 40 ppm and the minimum concentration used, which resulted in an increase in the PaO2/FIO2 ratio of at least 25%.
                Patients were followed up for 30 days or until death, and bronchoalveolar lavage (BAL) was performed at 0, 24, and 72 hrs. Nitric oxide synthase activity was measured spectrophotometrically, and myeloperoxidase, elastase, interleukin-8, and leukotrienes were measured in BAL fluid by enzyme immunoassay. Total nitrite and lipid peroxides in serum were measured colorimetrically. Nitric oxide synthase activity decreased (p = .01) and total nitrite increased (p = .02) in patients receiving inhaled nitric oxide. Other markers of inflammation in BAL fluid did not change. Lipid peroxide concentrations also did not alter.
                The decrease in activity of nitric oxide synthase in patients receiving nitric oxide is likely to be the result of feedback inhibition of the enzyme. This study shows that inhaled nitric oxide has no effect on several markers of the inflammatory response system and does not lead to increased oxidant stress.
Inhaled analgesia appears to be effective in reducing pain intensity and in giving pain relief in labour. However, substantial heterogeneity was detected for pain intensity. Furthermore, nitrous oxide appears to result in more side effects compared with flurane derivatives. Flurane derivatives result in more drowsiness when compared with nitrous oxide. When inhaled analgesia is compared with no treatment or placebo, nitrous oxide appears to result in even more side effects such as nausea, vomiting, dizziness and drowsiness. There is no evidence for differences for any of the outcomes comparing one strength verus a different strength of inhaled analgesia, comparing different delivery systems or comparing inhaled analgesia with TENS.