Isoflurane plus nitrous oxide versus propofol for recording of motor evoked potentials after high frequency repetitive electrical stimulation

The goal of this study was to test the influence of two widespread techniques of general anesthesia on motor evoked potentials (MEP) in response to transcranial and direct cortical high frequency repetitive electrical stimulation. Total intravenous anesthesia (TIVA) based on propofol and alfentanil was examined in 17 patients (group A), and balanced anesthesia (BA), based on nitrous oxide, isoflurane and fentanyl, was studied in 13 patients (group B). Distinct motor responses were available in 15 of 17 patients (88%) of group A, and in one of 13 patients (8%) of group B. Amplitudes increased significantly with increasing stimulus intensity and number of pulses under conditions of TIVA. At the same time, latencies decreased significantly with increasing stimulus intensity and decreasing interstimulus interval, but not with increasing number of pulses. It is hypothesized that propofol suppresses corticospinal I-waves at the cortical level, resulting in a conduction block at the level of the α-motoneuron, and that this effect may be overcome by high frequency repetitive stimulation. In contrast, nitrous oxide and isoflurane seem to have an additional suppressive effect on corticospinal D-waves, which may be overcome by higher stimulation intensity. In conclusion, transcranial high frequency repetitive stimulation and TIVA provide a feasible setting for intraoperative MEP monitoring, while higher doses of nitrous oxide and isoflurane are not compatible with recording of muscular activity elicited by the stimulation technique as described.     

Reproduction and fetal development in rats exposed to nitrous oxide

The effects of 24 hours of nitrous oxide exposure on reproductive indices and fetal development were examined in Sprague-Dawley rats. Four different experiments employing four concentrations of nitrous oxide--0.75%, 7.5%, 25% and 75%--established that the threshold of toxicity was greater than 25%. At 75% nitrous oxide there was a significant increase in early and late resorptions, and a consistent teratogenic effect (e.g., runts, ocular malformations, limb deformities). Neither the stress of shipping dams while pregnant nor the withholding of food during nitrous oxide exposure resulted in additional adverse effects. Exposure to 25% nitrous oxide was associated with increased deoxyuridine suppression values; however, adverse reproductive effects were not seen at this nitrous oxide concentration. The results of this and other studies which have examined the reproductive and teratogenic effects of nitrous oxide do not contraindicate its use in operating rooms nor, when necessary, as an anesthetic for pregnant surgical patients.     

Does halothane anaesthesia decrease the metabolic and endocrine stress responses of newborn infants undergoing operation?

Concern about the side effects of various anaesthetic agents in newborn infants has led to the widespread use of anaesthesia with unsupplemented nitrous oxide and oxygen with muscle relaxants in such patients. To investigate the efficacy of such a regimen 36 neonates undergoing operations were randomised to two groups: one group received anaesthesia with nitrous oxide and curare alone and the other was additionally given halothane. Concentrations of metabolites and hormones were measured before and at the end of operation and at six, 12, and 24 hours after operation and the values compared between the two groups. Neonates given halothane anaesthesia showed decreased hormonal responses to operation, with significant differences between the two groups in the changes in adrenaline, noradrenaline, and cortisol concentrations and the ratio of insulin to glucagon concentration. Changes in blood concentrations of glucose and total ketone bodies and plasma concentrations of non-esterified fatty acids were also decreased in neonates receiving halothane anaesthesia. Neonates given anaesthesia with unsupplemented nitrous oxide showed significantly greater increases in the urinary ratio of 3-methylhistidine to creatinine concentration and their clinical condition was also more unstable during and after operation.Unless specifically contraindicated potent anaesthesia with halothane or other anaesthetic agents should be given to all neonates undergoing surgical operations as it decreases their stress responses and improves their clinical stability during and after operation.     

Nitrous oxide may not increase the risk of cancer recurrence after colorectal surgery: a follow-up of a randomized controlled trial

Background

Even the best cancer surgery is usually associated with minimal residual disease. Whether these remaining malignant cells develop into clinical recurrence is at least partially determined by adequacy of host defense, especially natural killer cell function. Anesthetics impair immune defenses to varying degrees, but nitrous oxide appears to be especially problematic. We therefore tested the hypothesis that colorectal-cancer recurrence risk is augmented by nitrous oxide administration during colorectal surgery.

Methods

We conducted a 4- to 8-year follow-up of 204 patients with colorectal cancer who were randomly assigned to 65% nitrous oxide (n = 97) or nitrogen (n = 107), balanced with isoflurane and remifentanil. The primary outcome was the time to cancer recurrence. Our primary analysis was a multivariable Cox-proportional-hazards regression model that included relevant baseline variables. In addition to treatment group, the model considered patient age, tumor grade, dissemination, adjacent organ invasion, vessel invasion, and the number of nodes involved. The study had 80% power to detect a 56% or greater reduction in recurrence rates (i.e., hazard ratio of 0.44 or less) at the 0.05 significance level.

Results

After adjusting for significant baseline covariables, risk of recurrence did not differ significantly for nitrous oxide and nitrogen, with a hazard ratio estimate (95% CI) of 1.10 (0.66, 1.83), P = 0.72. No two-way interactions with the treatment were statistically significant.

Conclusion

Colorectal-cancer recurrence risks were not greatly different in patients who were randomly assigned to 65% nitrous oxide or nitrogen during surgery. Our results may not support avoiding nitrous oxide use to prevent recurrence of colorectal cancer.

Implications Statement

The risk of colorectal cancer recurrence was similar in patients who were randomly assigned to 65% nitrous oxide or nitrogen during colorectal surgery.

Trial Registration

Current Controlled Clinical Trials NCT00781352 http://www.clinicaltrials.gov     

Bilateral Thoracic Outlet Syndrome from Anomalous 8th Cervical Vertebrae Ribs

Thoracic outlet syndrome (TOS) is a group of diverse disorders resulting from compression of neurovascular structures as they pass from the lower neck to upper limb. Neurological symptoms, such as pain, weakness, or paraesthesia, are much more common than vascular symptoms such as pallor or venous congestion. Anatomical abnormalities can contribute to this condition. Thirty percent of patients with TOS can have a cervical rib, arising from the transverse process of the 7th cervical vertebra, compared with 1% of the general population. We report the first case in the literature of neurogenic TOS from a cervical rib arising from a supernumerary 8th cervical vertebra. This patient had immediate improvement in TOS symptoms following scalene muscle surgery and resection of cervical and first thoracic ribs.     

Nitrous oxide emissions from a gully mire in mid-Wales, UK, under simulated summer drought

Certain general circulation models predict that a doubling of atmospheric carbon dioxide concentrations will increase the frequency of summer drought in northern wetlands due to hotter, drier summers. There is currently much uncertainty as to how drought will affect emissions of the greenhouse gas, nitrous oxide, from wetlands. We have demonstrated that an eight centimetre drawdown of the water table in a gully mire does not significantly affect nitrous oxide emissions from this site. However, under a more extreme drought scenario carried out on peat monoliths, nitrous oxide emissions increased exponentially with a linear decrease in water table height. Drought caused a significant increase in nitrous oxide productionbelow the water table but most of the total increase could be attributed to increased emissionsabove the water table. Results from an acetylene block experiment suggested that increased emissions were caused by increased nitrous oxide production from denitrification, rather than by increased production from nitrification. In the laboratory study, drought severity had no effect on peatwater nitrate concentrations below the water table, however, increasing drought severity decreased ammonium concentrations.     

The effects of nitrous oxide on the developing hamster embryos

Pregnant hamsters were exposed to different concentrations of nitrous oxide during the period of organogenesis. Teratogenic effects were observed in a small but significant number of fetuses. Types of malformations included cleft palate, limb defects, gut herniation, and fetal edema. A dose-effect relationship was not observed. It is not clear from our observations whether the observed effect on the fetuses was due to the excess of nitrous oxide, hypoxia, or a combination of both. Comparison with published literature indicates that further studies on the effects of nitrous oxide in placental animals are needed.     

Denitrification by Azospirillum brasilense Sp 7

Nitrous oxide reduction can consistently be demonstrated with high activities in cells of Azospirillum brasilense Sp 7 which are grown anaerobically in the presence of low amounts of nitrite. Azospirillum can even grow anaerobically with nitrous oxide in the absence of any other respiratory electron acceptor. Nitrous oxide reduction by Azospirillum is inhibited by acetylene, amytal and weakly by carbon monoxide. Azospirillum converts nitrous oxide to molecular nitrogen without the formation of ammonia. The cells must, therefore, be supplied with ammonia from nitrogen fixation during anaerobic growth with nitrous oxide. When no other nitrogen compound besides nitrous oxide is available in the medium, the bacteria synthesize nitrogenase from protein reserves in about 2 h. Nitrogenase synthesis is blocked by chloramphenicol under these conditions. In contrast, the addition of nitrate or nitrite to the medium represses the synthesis of nitrogenase. Nitrous oxide reduction by Azospirillum and other microorganisms is possibly of ecological significance, because the reaction performed by the bacteria may remove nitrous oxide from soils.     

Comparison of denitrification by Pseudomonas stutzeri, Pseudomonas aeruginosa, and Paracoccus denitrificans.

A comparison was made of denitrification by Pseudomonas stutzeri, Pseudomonas aeruginosa, and Paracoccus denitrificans. Although all three organisms reduced nitrate to dinitrogen gas, they did so at different rates and accumulated different kinds and amounts of intermediates. Their rates of anaerobic growth on nitrate varied about 1.5-fold; concomitant gas production varied more than 8-fold. Cell yields from nitrate varied threefold. Rates of gas production by resting cells incubated with nitrate, nitrite, or nitrous oxide varied 2-, 6-, and 15-fold, respectively, among the three species. The composition of the gas produced also varied markedly: Pseudomonas stutzeri produced only dinitrogen; Pseudomonas aeruginosa and Paracoccus denitrificans produced nitrous oxide as well; and under certain conditions Pseudomonas aeruginosa produced even more nitrous oxide than dinitrogen. Pseudomonas stutzeri and Paracoccus denitrificans rapidly reduced nitrate, nitrite, and nitrous oxide and were able to grow anaerobically when any of these nitrogen oxides were present in the medium. Pseudomonas aeruginosa reduced these oxides slowly and was unable to grow anaerobically at the expense of nitrous oxide. Furthermore, nitric and nitrous oxide reduction by Pseudomonas aeruginosa were exceptionally sensitive to inhibition by nitrite. Thus, although it has been well studied physiologically and genetically, Pseudomonas aeruginosa may not be the best species for studying the later steps of the denitrification pathway.     

Limb-sparing surgery with reinnervated free-muscle transfer following radical excision of soft-tissue sarcoma in the extremity.

Limb-sparing surgery is the preferred approach in the management of patients with high-grade soft-tissue sarcomas when local disease can be completely resected. However, conventional treatment focuses only on restoration of basic functions to the remnant limb. Lost functions are not restored to normal, leaving the patient with variable degrees of functional disabilities. This in turn may necessitate further massive reconstructive procedures. Transferred reinnervated free muscles were used to reconstruct functions lost after radical resection of malignant soft-tissue sarcoma of the extremities in 17 patients. The long-term functional outcome included survival of transplanted muscle, speed of neural recovery, and muscle strength and disabilities. All muscles survived. Postoperative follow-up ranged from 27 to 106 months. All muscles except those in a 75-year-old patient were successfully reinnervated. Powerful strength and almost normal limb functions were obtained. Functional scoring of the patients according to the rating system of the Musculoskeletal Tumor Society was 87 percent for the lower extremity and 93 percent for the upper extremity. All patients are presently disease-free. Use of the reinnervated free-muscle transfer in limb-sparing surgery after resection of soft-tissue sarcoma in the extremity may be indicated in the young adult when radical excision of the tumor will result in severe motor functional loss, provided adequate clearance can be obtained and that there is no presence of distant metastasis.     

Comparison of denitrification by Pseudomonas stutzeri, Pseudomonas aeruginosa, and Paracoccus denitrificans

A comparison was made of denitrification by Pseudomonas stutzeri, Pseudomonas aeruginosa, and Paracoccus denitrificans. Although all three organisms reduced nitrate to dinitrogen gas, they did so at different rates and accumulated different kinds and amounts of intermediates. Their rates of anaerobic growth on nitrate varied about 1.5-fold; concomitant gas production varied more than 8-fold. Cell yields from nitrate varied threefold. Rates of gas production by resting cells incubated with nitrate, nitrite, or nitrous oxide varied 2-, 6-, and 15-fold, respectively, among the three species. The composition of the gas produced also varied markedly: Pseudomonas stutzeri produced only dinitrogen; Pseudomonas aeruginosa and Paracoccus denitrificans produced nitrous oxide as well; and under certain conditions Pseudomonas aeruginosa produced even more nitrous oxide than dinitrogen. Pseudomonas stutzeri and Paracoccus denitrificans rapidly reduced nitrate, nitrite, and nitrous oxide and were able to grow anaerobically when any of these nitrogen oxides were present in the medium. Pseudomonas aeruginosa reduced these oxides slowly and was unable to grow anaerobically at the expense of nitrous oxide. Furthermore, nitric and nitrous oxide reduction by Pseudomonas aeruginosa were exceptionally sensitive to inhibition by nitrite. Thus, although it has been well studied physiologically and genetically, Pseudomonas aeruginosa may not be the best species for studying the later steps of the denitrification pathway.     

Postoperative changes in serum cytokines profile and nitric oxide levels in patients with cystic echinococcosis

The aim of the present study was to examine serum cytokines and nitric oxide (NO) levels in patients with cystic echinococcosis (CE). 28 patients with CE were studied and all underwent surgery. Serum levels of tumour necrosis factor-alpha (TNF-alpha), interleukin IL-1beta, receptor of soluble IL-2R (sIL-2R), IL-6, IL-8, nitrate/nitrite, and C-reactive protein (CRP) were determined before and after induction of treatment. Data were compared with those obtained from 28 healthy volunteers. IL-6 was elevated in all CE patients (100%). IL-8 was increased in 11/28 (39.3%). Increased levels of IL-2R and TNF-alpha were found in a limited number of them particularly those showing cysts in the central area of the liver (5/28, 6/28). IL-1beta level was not elevated in any patient except in secondary severe CE. CRP and nitrate/nitrite levels were also increased. A positive correlation between CRP and IL-6 (r = 0.74; p < 0.001) was found confirming the link between inflammation due to CE and activation of monocytes. All patients completely recovered and the levels of the studied parameters reverted to normal levels except one patient in whom severe recurrent disease occurred two years after the first operation. These results suggest that there are different immunoregulatory events and cytokines response during CE and may be in part related to slight monocytosis and in part to Th2 activation. IL-6, NO and CRP were unambiguously involved in the host parasite interaction and therefore may be useful markers in monitoring CE management and evaluating surgical stress.     

Prevention of Early Postoperative Deep Vein Thrombosis by Passive Exercise of Leg during Surgery

A clinical trial assessed the effect of passive exercise of the lower limb during surgery on the incidence of early postoperative deep vein thrombosis. Thrombosis was diagnosed by means of the ¹²⁵I-fibrinogen uptake test. Passive exercise of the lower limb during the operation was achieved by using a motorized foot mover designed for use on supine subjects, and by pedalling only one leg each patient acted as his own control.In a sequential statistical analysis, 47 patients were required to reach the 5% level of significance. Thrombosis was detected in 11 control (unpedalled) legs alone, and in only one pedalled leg alone. Two patients developed thrombosis bilaterally. The investigation shows that the incidence of early thrombosis in legs which were exercised during surgery was reduced by 77%.     

Nonspecific immunoglobulin synthesis and elevated IgG levels in rabbits immunized with mucoid exopolysaccharide from cystic fibrosis isolates of Pseudomonas aeruginosa

Correlations have been observed between the presence of elevated levels of serum IgG and poor clinical status in cystic fibrosis, and between colonization with mucoid exopolysaccharide (MEP)-producing strains of Pseudomonas aeruginosa and poor clinical status. To determine if P. aeruginosa products could affect the immune system in such a way as to cause nonspecific Ig synthesis and elevated IgG levels, we immunized rabbits with whole bacterial cells and purified MEP from three strains of mucoid P. aeruginosa and with cells of a mucoid strain of E. coli. Antisera raised to whole bacterial cells reacted slightly with a panel of 12 different polysaccharide antigens from various bacteria, whereas antisera raised to purified MEP reacted moderately to strongly with these antigens. The heterologous antibodies elicited by MEP generally showed high affinities and specificities for heterologous antigens, and were functional in opsonophagocytic assays. Analysis of the kinetics of rabbit responses to MEP against homologous and heterologous antigens suggested that nonspecific Ig synthesis could be documented shortly after homologous antibody to MEP was elicited. Rabbits hyperimmunized with MEP also had elevated levels of IgG, even after removal of MEP-specific antibody. These data suggest that the change in young cystic fibrosis patients from a relatively healthy, hypogammaglobulinemic state to more progressive lung disease, associated with elevated levels of IgG and colonization with mucoid P. aeruginosa, may be mediated, in part, by the effects of MEP on mammalian immune systems.     

Critical evaluation of endovascular surgery for limb salvage

Rest pain, tissue loss, and gangrene are manifestations of critical limb ischemia caused by peripheral arterial disease and define a patient subgroup at highest risk for major limb amputation. Patients with nonhealing lower extremity wounds should be screened for the risk factors for peripheral arterial disease and offered noninvasive vascular testing. The diagnosis of critical limb ischemia mandates prompt institution of medical and surgical management to achieve the best chance of limb salvage. Surgical intervention has evolved from primary amputation to open bypass to the present era of endovascular therapy. The goals of surgical bypass and endovascular therapy are to improve perfusion sufficiently to permit healing. Despite poorer patency rates and the more frequent need for reintervention, endovascular therapy has been shown in multiple retrospective studies to achieve limb salvage similar to open bypass. Only one large, prospective, randomized controlled trial exists comparing open bypass with endovascular therapy: The Bypass versus Angioplasty in Severe Limb Ischemia of the Leg (BASIL) trial. Close clinical surveillance and serial monitoring of limb perfusion by means of noninvasive arterial studies are needed to determine the need for further vascular intervention. Limb salvage patients suffer from multiple comorbidities and benefit from a multidisciplinary, team approach to care.     

Acetylene inhibition technique underestimates in situ denitrification rates in intact cores of freshwater sediment

Abstract Denitrification in intact sediment cores was measured by the acetylene inhibition technique and compared with the nitrate flux between water and sediment. Less than half of the nitrate-N consumed by the sediment could be recovered as nitrous oxide-N. The low recovery rate of nitrous oxide from intact sediment cores indicated losses of nitrous oxide by diffusion down to nitrate-free sediment layers, where reduction of nitrous oxide may take place. In sediment slurries 100% of nitrate-N could be recovered as nitrous oxide-N as long as the nitrate concentration in the liquid phase was above 10 μM. Nitrous oxide added to nitrate-free sediment slurries was reduced regardless of whether acetylene was present or not. Therefore denitrification may be significantly underestimated by this method.     

Methoxyflurane and Nitrous Oxide as Obstetric Analgesics. I.—A Comparison by Continuous Administration

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.     

Observations on Cardiac Arrythmias during Laparoscopy

The incidence of cardiac arrhythmias occurring during laparoscopy was studied in 100 consecutive patients who received carbon dioxide to inflate the abdomen and compared with that in 45 patients in whom nitrous oxide was substituted for carbon dioxide. Seventeen patients receiving carbon dioxide and two receiving nitrous oxide developed multiple arrhythmias, the commonest variety being fusion beats due to ventricular ectopic beats. Blood gas determinations showed that carbon dioxide caused a significantly higher level of Paco₂ and a lower pH than did nitrous oxide.     

Soft-tissue flap coverage maximizes limb salvage after allograft bone extremity reconstruction

Limb salvage after extremity tumor ablation may include the use of allograft bone. The primary complication of this method is infection of the allograft, which can lead to limb loss in up to 50 percent of cases. The purpose of this study is to evaluate the efficacy of primary muscle flap coverage in the setting of allograft bone limb salvage surgery. This study is a prospective review of all patients with flap coverage of extremity allografts over the 10-year period 1991 to 2001. There were 20 patients (11 male and nine female patients) with an average age of 28 years (range, 6 to 72 years). Flap coverage was primary in 16 patients and delayed in four. Delayed coverage was performed for failed wounds that did not have a primary soft-tissue flap. Pathologic findings included osteosarcoma in nine patients, Ewing sarcoma in five patients, malignant fibrohistiocytoma in two patients, chondrosarcoma in two patients, synovial sarcoma in one patient, and leiomyosarcoma in one patient. Allograft reconstruction was performed for the upper extremity in 12 patients and for the lower extremity in eight patients. Flap reconstruction was accomplished with 20 pedicle flaps in 17 patients (latissimus dorsi, 12; gastrocnemius, four; soleus, three; and fasciocutaneous flap, one) and four free flaps (rectus abdominis, three; latissimus dorsi, one) in four patients. All pedicled flaps survived. There was one flap failure in the entire series, which was a free rectus abdominis flap. This case resulted in the only limb loss noted. The follow-up period ranged from 1 to 50 months (average, 12.35 months). At the time of final follow-up, three patients were dead of disease and 17 were alive with intact extremities. The overall limb salvage rate in the setting of bone allograft and soft-tissue flap coverage was 95 percent (19 of 20). Reoperation for bone-related complications was required in 50 percent (two of four) of cases receiving delayed flap coverage compared with 19 percent (three of 16) of patients with primary flap coverage (statistically not significant). The results of this study support the use of soft-tissue flap coverage for allograft limb reconstruction. In this series, no limb was lost in the setting of a viable flap. Reoperation was markedly reduced in the setting of primary flap coverage. Pedicled or microvascular transfer of well-vascularized muscle can be used to wrap the allograft and minimize devastating wound complications potentially leading to loss of allograft and limb.     

Ethanol and nitrous oxide produce withdrawal-induced convulsions by similar mechanisms in mice

Twenty generations of selective breeding were used to produce lines (strains) of mice which differ markedly from one another in ethanol physical dependence development as indexed by handling-induced convulsions (HIC) induced by withdrawal from ethanol. These withdrawal seizure prone (WSP) and withdrawal seizure resistant (WSR) selection lines now differ by over 10-fold in HIC scores after equivalent exposure to intoxicating levels of ethanol via inhalation. Since handling-induced convulsions can be readily elicited following withdrawal from nitrous oxide, we sought to determine if the very large differences in ethanol withdrawal-induced HIC bred into these selection lines would generalize to nitrous oxide. Following a 60 min exposure to 75% nitrous oxide (in O2), a greater than 10-fold difference in HIC scores, and a 2-fold difference in tremor incidence was seen upon withdrawal in WSP vs. WSR mice. These findings closely parallel those seen with ethanol, and demonstrate that a large degree of commonality exists in the genes and the mechanisms determining these withdrawal signs. HIC elicited by nitrous oxide withdrawal were readily suppressed by ethanol, and HIC elicited by ethanol withdrawal were promptly suppressed by 75% nitrous oxide in WSP mice. Nitrous oxide also suppressed HIC and tremor associated with nitrous oxide withdrawal.