Comparison of non-invasive peripheral venous saturations with venous blood co-oximetry.

The estimation of venous oxygen saturations using photoplethysmography (PPG) may be useful as a noninvasive continuous method of detecting changes in regional oxygen supply and demand (e.g. in the splanchnic circulation). The aim of this research was to compare PPG-derived peripheral venous oxygen saturations directly with venous saturation measured from co-oximetry blood samples, to assess the feasibility of non-invasive local venous oxygen saturation. This paper comprises two similar studies: one in healthy spontaneously-breathing volunteers and one in mechanically ventilated anaesthetised patients. In both studies, PPG-derived estimates of peripheral venous oxygen saturations (SxvO2) were compared with co-oximetry samples (ScovO2) of venous blood from the dorsum of the hand. The results were analysed and correlation between the PPG-derived results and co-oximetry was tested for. In the volunteer subjects,moderate correlation (r = 0.81) was seen between SxvO2 values and co-oximetry derived venous saturations (ScovO2), with a mean (±SD) difference of +5.65 ± 14.3% observed between the two methods. In the anaesthetised patients SxvO2 values were only 3.81% lower than SpO2 and tended to underestimate venous saturation (mean difference = -2.67 ± 5.89%) while correlating weakly with ScovO2 (r = 0.10). The results suggest that significant refinement of the technique is needed to sufficiently improve accuracy to produce clinically meaningful measurement of peripheral venous oxygen saturation. In anaesthetised patients the use of the technique may be severely limited by cutaneous arteriovenous shunting.

Normalization of widespread hyperesthesia and facilitated spatial summation of deep-tissue pain in knee osteoarthritis patients after knee replacement.

OBJECTIVE: The modest association between radiographic joint damage and pain in osteoarthritis (OA) has led to the suggestion of facilitated central pain processing. This study evaluated the importance of ongoing tissue pathology in the maintenance of enhanced central pain processing. METHODS: Pain assessment was performed on 48 patients with symptomatic knee OA and 21 sex- and age-matched pain-free healthy control subjects. Twenty of the OA patients subsequently underwent total knee replacement surgery and were reassessed. Pressure-pain thresholds (PPTs) were recorded using a pressure algometer (both over and distant from the knee) and a double-chamber inflatable cuff mounted around the calf. Spatial summation was assessed by relating PPTs using the dual- and single-chamber cuff. Conditioned pain modulation (CPM) was assessed by recording the increase in PPT in response to experimental arm pain. RESULTS: PPTs at the knee and at sites away from the knee were reduced in OA patients as compared with healthy pain-free control subjects (P < 0.0001). Cuff PPTs were decreased in OA patients as compared with the healthy controls (P < 0.05), who also exhibited a greater degree of spatial summation (P < 0.05). Whereas an elevation of PPTs was noted in the healthy controls in response to experimental arm pain (P < 0.0001), no such CPM was observed in the OA patients. Following joint replacement in the OA patients, there was a reduction in the widespread mechanical hyperesthesia, along with normalization of spatial summation ratios and restoration of CPM. CONCLUSION: The widespread hyperesthesia and enhanced spatial summation observed in OA patients imply sensitized central pain mechanisms together with the loss of CPM. Normalization of the results following joint replacement implies that these central pain processes are maintained by peripheral input.

Investigation of photoplethysmographic signals and blood oxygen saturation values obtained from human splanchnic organs using a fiber optic sensor.

OBJECTIVE: A reliable, continuous method of monitoring splanchnic organ oxygen saturation could allow for the early detection of malperfusion, and may prevent the onset of multiple organ failure. Current monitoring techniques have not been widely accepted in critical care monitoring. As a preliminary to developing a continuous indwelling device, this study evaluates a new handheld fiber optic photoplethysmographic (PPG) sensor for estimating the blood oxygen saturation (SpO(2)) of splanchnic organs during surgery. METHODS: A fiber optic splanchnic PPG sensor, instrumentation system and virtual instrument were developed to facilitate PPG and SpO(2) measurement from splanchnic organs. Following Local Research Ethics Committee approval, the sensor was evaluated on seventeen ASA 1 and 2 patients undergoing open laparotomy. PPG signals were obtained from the large bowel, small bowel, liver and stomach. Simultaneous PPG signals from the finger were also obtained using an identical fiber optic sensor. RESULTS: Good quality PPG signals with high signal-to-noise (SNR) ratios were obtained from all splanchnic sites under investigation. Analysis of the ac and dc amplitudes of the red and infrared PPG signals showed there to be a statistically significant difference between PPG signals obtained from splanchnic organs with those obtained from the finger (using fiber optic sensors). Estimated SpO(2) values from the splanchnic organs show good agreement with those obtained from the finger using both a fiber optic sensor and a commercial device. Furthermore, the results of a Bland and Altman analysis indicate that fiber optic splanchnic pulse oximetry, particularly of the bowel, may provide a suitable method for monitoring splanchnic organ perfusion. CONCLUSION: The evaluation of a new fiber optic sensor on anaesthetized patients undergoing laparotomy demonstrated that good quality PPG signals and SpO(2) estimates can be obtained from splanchnic organs. Such a sensor may provide a useful tool for the intraoperative assessment of splanchnic perfusion.

Physical and chemical characterization of dentin surface following treatment with NovaMin technology.

OBJECTIVE: The aim of this study was to characterize, in vitro, the mode of action of calcium sodium phosphosilicate (NovaMin) in occluding dentin tubules for the purpose of treating dentin hypersensitivity. METHODS: Calcium sodium phosphosilicate (CSPS) was combined with artificial saliva on surfaces of prepared dentin discs. The layer formed was initially examined by a scanning electron microscope (SEM). Focused ion beam (FIB) milling was used to make bulk cross-sections and thin film lamellae. Low kV scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDS), and selected area electron diffraction were then used to characterize, chemically and structurally, the layer formed and the material occluding the tubules. Experiments were also performed to assess the suitability of using an environmental scanning electron microscope (ESEM) in wet mode to follow the transition from CSPS to hydroxyapatite. RESULTS: SEM imaging showed that a layer was formed on the treated dentin samples, and that this layer occluded tubules. Chemical and structural analysis of this material showed that it was hydroxyapatite-like. The wet mode ESEM experiments demonstrated that this technique has the potential to follow the transition from CSPS to the crystalline hydroxyapatite material. CONCLUSION: The use of modern imaging and analysis techniques has demonstrated, in vitro, the reaction of CSPS from an amorphous material to a crystalline hydroxyapatite-like material. These experiments confirmed an occlusion mode of action for CSPS for the treatment of dentin hypersensitivity.

Physical and chemical characterization of the surface layers formed on dentin following treatment with a fluoridated toothpaste containing NovaMin.

OBJECTIVE: To characterize in vitro the formation and robustness of a layer formed on dentin following treatment with a fluoridated toothpaste containing calcium sodium phosphosilicate (NovaMin) using modem imaging and analysis techniques. METHODS: Calcium sodium phosphosilicate (CSPS)-containing toothpaste was brushed on to etched dentin specimens twice daily for up to five days. In between applications the samples were stored in artificial saliva. Additionally, certain samples underwent a chemical challenge in the form of a dietary acid, whereby samples were exposed to a cola or grapefruit juice beverage for five minutes on day 4 of the five-day study. The ability of the CSPS-containing formulation to occlude tubules was assessed visually by scanning electron microscope (SEM) imaging and compared to a water control. In a second experiment, the mechanical resistance of the layer was assessed using profilometry after controlled brushing for 200 brush strokes with a wet medium-bristled toothbrush. To visualize the layer and characterize the tubule occlusion, longitudinal cross-sections were prepared using a focused ion beam scanning electron microscope (FIB SEM), and analysis performed by energy dispersive x-ray spectroscopy (EDS) and electron diffraction. Owing to the complexity of the mixed material deposited after application of the toothpaste, material from inside a dentin tubule was selectively removed after five days of treatment, and the morphologically different materials imaged and analyzed by electron diffraction in the transmission electron microscope (TEM). RESULTS: SEM inspection showed significant coverage of the dentin samples after application of CSPS toothpaste for all five days, in contrast to the water control where the majority of tubules remained open after all five days. Exposure of the NovaMin-treated samples to common dietary acids did not lead to re-exposure of the tubules. Profilometry measurements demonstrated an intact layer covering the dentin surface after one and five days. EDS analysis and electron diffraction indicated the layer and the material plugging the tubule to be a calcium phosphate material with a crystallographic structure similar to hydroxyapatite. CONCLUSION: CSPS contained in toothpaste formulations adhered to exposed dentin surfaces. The layer formed was resistant to acid and mechanical challenges. Characterization of this layer indicated it was hydroxyapatite-like in nature.

A comparison of the respiratory effects of oxycodone versus morphine: a randomised, double-blind, placebo-controlled investigation.

Oxycodone's respiratory profile (particularly the extent of respiratory depression in comparison to morphine) remains to be fully characterised in the peri-operative period. We randomly assigned ASA 1-2 adults for elective surgery under general anaesthesia to receive saline, morphine 0.1 mg.kg⁻¹, or oxycodone 0.05 mg.kg⁻¹, 0.1 mg.kg⁻¹, or 0.2 mg.kg(-1) . Results were obtained from six patients in the saline group, 12 patients in the groups receiving morphine 0.1 mg.kg⁻¹, oxycodone 0.05 mg.kg⁻¹ and 0.1 mg.kg⁻¹, and from 10 patients who received oxycodone 0.2 mg.kg⁻¹. Patients were breathing spontaneously and minute ventilation monitored with a wet wedge spirometer for 30 min. All active groups demonstrated significant respiratory depression compared to saline (p < 0.0001 for all groups). The mean (SD) reduction in minute volume from baseline was 22.6% (10.4%) for the morphine 0.1 group and 53.3% (27.2%), 74.4% (12.9%) and 88.6% (13.5%) for the oxycodone 0.05, 0.1 and 0.2 groups, respectively, with significant dose dependent differences between oxycodone groups (p = 0.0007). The extent and speed of onset of oxycodone induced respiratory depression was dose dependent and greater than an equivalent dose of morphine.

Pain assessment and management in medical wards: an area of unmet need.

BACKGROUND: Acute Pain Services (APS) were introduced primarily to improve postoperative pain management. Although pain is similar in prevalence and severity in medical and surgical wards, its assessment and management in non-surgical patients often receives less attention and resources. OBJECTIVE: To investigate the extent of APS involvement on medical wards and obtain perceptions of deficiencies. METHOD: A questionnaire was mailed to APS leads in 287 UK NHS hospitals; 229 questionnaires were returned (79.8% response). RESULTS: Only 36 (16%) of the 225 hospitals with medical wards reported routine APS involvement. Pain scores were not recorded in 75 (33%) hospitals, 11 (5%) denied knowledge about assessments being conducted, and 185 (82.2%) respondents felt that pain management on medical wards was inadequate. CONCLUSIONS: Perceived lack of training and awareness of healthcare staff were highly ranked contributing factors, and this was attributed to inadequate funding. This study highlights the scope for improvement of pain control in medical patients, with benefits from reduced morbidity and faster recovery.

Cerebral arterial oxygen saturation measurements using a fiber-optic pulse oximeter.

BACKGROUND: A pilot investigation was undertaken to assess the performance of a novel fiber-optic cerebral pulse oximetry system. A fiber-optic probe designed to pass through the lumen of a cranial bolt of the type used to make intracranial pressure measurements was used to obtain optical reflectance signals directly from brain tissue. METHODS: Short-duration measurements were made in six patients undergoing neurosurgery. These were followed by a longer duration measurement in a patient recovering from an intracerebral hematoma. Estimations of cerebral arterial oxygen saturation derived from a frequency domain-based algorithm are compared with simultaneous pulse oximetry (SpO2) and hemoximeter (SaO2) blood samples. RESULTS: The short-duration measurements showed that reliable photoplethysmographic signals could be obtained from the brain tissue. In the long-duration study, the mean (±SD) difference between cerebral oxygen saturation (ScaO2) and finger SpO2 (in saturation units) was -7.47(±3.4)%. The mean (±SD) difference between ScaO2 and blood SaO2 was -7.37(±2.8)%. CONCLUSIONS: This pilot study demonstrated that arterial oxygen saturation may be estimated from brain tissue via a fiber-optic pulse oximeter used in conjunction with a cranial bolt. Further studies are needed to confirm the clinical utility of the technique.

Investigation of dentinal tubule occlusion using FIB-SEM milling and EDX.

OBJECTIVE: The aim of this study was to evaluate in vitro the dentin tubule occluding effect of an 8% strontium acetate dentifrice (Sensodyne Rapid Relief) compared to patent dentin tubules using modern sample preparation, imaging, and analysis techniques. METHODS: Etched dentin discs, either untreated or treated with the dentifrice, were analyzed by preparing cross-sections using focused ion beam scanning electron microscopy (FIB-SEM) milling, and the strontium presence mapped using energy dispersive X-ray spectroscopy (EDX). RESULTS: Surface imaging showed the dentifrice had coated the treated sample. Sub-surface information gained by preparing longitudinal cross-sections of the treated samples showed the tubule openings to be plugged, and EDX mapping of the cross-section confirmed enhanced strontium levels within the tubules several microns below the treatment surface. CONCLUSION: The combination of modern sample preparation, imaging, and analysis techniques employed in this study has shown that the 8% strontium acetate dentifrice occludes dentin tubules. EDX analysis has shown the presence of strontium within the dentin tubules, with elemental maps illustrating how the strontium has been incorporated into the dentin.

In situ lift-out: steps to improve yield and a comparison with other FIB TEM sample preparation techniques.

Steps to improve the success yield of the in situ lift-out technique are presented. These include tapping the plinth of the system and monitoring the grounding current to check the lift-out needle is fixed to the material being removed. In addition, the relative success yields and the time to prepare a TEM lamella for the three main FIB methods are discussed and compared.

Preliminary evaluation of a new fibre-optic cerebral oximetry system.

A new system for measuring the oxygen saturation of blood within tissue has been developed, for a variety of patient monitoring applications. A particular unmet need is in the central nervous system, and this project aims to devise a means for measuring blood oxygen saturation in the brain tissue of patients recovering from neurosurgery or head injury. Coupling light sources and a photodetector to optical fibres results in a probe small enough to pass through a cranial bolt of the type already in use for intra-cranial pressure monitoring. The development and evaluation of a two-wavelength fibre-optic reflectance photoplethysmography (PPG) system are described. It was found that good quality red and near-infrared PPG signals could be obtained from the finger using a fibre-optic probe. Experiments were conducted to find the inter-fibre spacings that yield signals most suitable for calculating oxygen saturation. Reliable signals could be obtained for inter-fibre spacings between 2 mm and 5 mm, the latter being the size of the maximum aperture in the cranial bolt. A preliminary measurement from human brain tissue is also presented.

Selective cyclooxygenase inhibition: its role in pain and anaesthesia.

Cyclooxygenase inhibitors reduce inflammation and hyperalgesia by decreasing prostaglandin E2 production. Traditional NSAIDs (inhibiting both COX-1 and 2) though ubiquitous in peri-operative pain practice, have well-known gastrointestinal (GI), cardiovascular and other risks. This article systematically addresses the main efficacy and safety issues pertaining to NSAID and selective COX-2 inhibitors (coxibs) use, focusing on the acute pain context, particularly post-operative pain management. NSAIDs and coxibs are of proven analgesic efficacy in post-operative pain control, and their opioid-sparing role in multimodal analgesia, leads to significantly reduced opioid related side effects. Although GI risk is regarded as less of an issue in short-term therapy, in patients with a past history of peptic ulceration who are denied NSAIDs, coxibs may be considered a suitable alternative. In the peri-operative setting, coxibs confer an additional advantage over NSAIDs by preserving the platelet thromboxane production and clotting. Cardiovascular safety has been assessed for the parenteral parecoxib and its active moiety valdecoxib, and was found to be satisfactory in major non-cardiac surgery, but increased thromboembolic complications occurred in coronary artery bypass surgery leading to contra-indication for this type of surgery. Coxibs and NSAIDs have similar renal effects and caution or avoidance is required with renal disease or reduced peri-operative renal perfusion. Coxibs may be safer in aspirin-sensitive asthmatics. Bone healing effects remain controversial, but only a few days therapy appears to be safe.

Focused ion beam nanofabrication: a comparison with conventional processing techniques.

Focused ion beam and dual platform systems are versatile tools for nanoengineering and nanoscience applications. These systems complement conventional processing methods and can be used to prototype and modify a diverse range of nano-devices and sensors. This article discusses FIB nanofabrication and compares it with other fabrication techniques such as electron beam lithography and reactive ion etching. Aspects such as the minimum feature size and side wall profiles are discussed and compared. In addition, the limitations and detrimental effects of FIB processes are discussed.

Fabrication of nickel nanocontacts using nanostencils and electron beam assisted SiO2 deposition.

Nickel nanocontacts for studying ballistic magnetoresistance have been fabricated by sputtering through FIB prepared nanostencil masks and by using electron beam assisted deposition of SiO2 to reduce the size of FIB milled pores through silicon nitride membranes. These two methods are discussed in terms of the nanocontact sizes, fabrication, and yield. The smallest size of the nanocontacts prepared using the nanostencil method was 40 nm and by the filling method was 1-2 nm. The maximum magnetoresistance measured was 1% and no evidence of a large ballistic magnetoresistance was observed.

Filtering techniques for the removal of ventilator artefact in oesophageal pulse oximetry.

The oesophagus has been shown to be a reliable site for monitoring blood oxygen saturation (SpO(2)). However, the photoplethysmographic (PPG) signals from the lower oesophagus are frequently contaminated by a ventilator artefact making the estimation of SpO(2) impossible. A 776th order finite impulse response (FIR) filter and a 695th order interpolated finite impulse response (IFIR) filter were implemented to suppress the artefact. Both filters attenuated the ventilator artefact satisfactorily without distorting the morphology of the PPG when processing recorded data from ten cardiopulmonary bypass patients. The IFIR filter was the better since it conformed more closely to the desired filter specifications and allowed real-time processing. The average improvements in signal-to-noise ratio (SNR) achieved by the FIR and IFIR filters for the fundamental component of the red PPG signals with respect to the fundamental component of the artefact were 57.96 and 60.60 dB, respectively. The corresponding average improvements achieved by the FIR and IFIR filters for the infrared PPG signals were 54.83 and 60.96 dB, respectively. Both filters were also compared with their equivalent tenth order Butterworth filters. The average SNR improvements for the FIR and IFIR filters were significantly higher than those for the Butterworth filters.

Prevalence of chronic pain in the UK: a systematic review and meta-analysis of population studies.

OBJECTIVES: There is little consensus regarding the burden of pain in the UK. The purpose of this review was to synthesise existing data on the prevalence of various chronic pain phenotypes in order to produce accurate and contemporary national estimates. DESIGN: Major electronic databases were searched for articles published after 1990, reporting population-based prevalence estimates of chronic pain (pain lasting >3 months), chronic widespread pain, fibromyalgia and chronic neuropathic pain. Pooled prevalence estimates were calculated for chronic pain and chronic widespread pain. RESULTS: Of the 1737 articles generated through our searches, 19 studies matched our inclusion criteria, presenting data from 139 933 adult residents of the UK. The prevalence of chronic pain, derived from 7 studies, ranged from 35.0% to 51.3% (pooled estimate 43.5%, 95% CIs 38.4% to 48.6%). The prevalence of moderate-severely disabling chronic pain (Von Korff grades III/IV), based on 4 studies, ranged from 10.4% to 14.3%. 12 studies stratified chronic pain prevalence by age group, demonstrating a trend towards increasing prevalence with increasing age from 14.3% in 18-25 years old, to 62% in the over 75 age group, although the prevalence of chronic pain in young people (18-39 years old) may be as high as 30%. Reported prevalence estimates were summarised for chronic widespread pain (pooled estimate 14.2%, 95% CI 12.3% to 16.1%; 5 studies), chronic neuropathic pain (8.2% to 8.9%; 2 studies) and fibromyalgia (5.4%; 1 study). Chronic pain was more common in female than male participants, across all measured phenotypes. CONCLUSIONS: Chronic pain affects between one-third and one-half of the population of the UK, corresponding to just under 28 million adults, based on data from the best available published studies. This figure is likely to increase further in line with an ageing population.

Evaluation of oesophageal reflectance pulse oximetry in major burns patients.

Pulse oximetry is being used in everyday clinical practice in anaesthesia utilising a peripheral probe. However, it may be unreliable in certain clinical situations such as hypothermia, hypovolemia, vasoconstriction and decreased cardiac output. Similar situations occur in burns patients and, more importantly, burns to extremities which limit the sites available for measurement of peripheral oxygen saturation (SpO(2)). To overcome these limitations, the oesophagus has been investigated as an alternative measurement site, as perfusion may be preferentially preserved centrally. A miniaturised reflectance oesophageal saturation (SpO(2)) probe has been constructed utilising infrared and red photodiodes and a photodetector. Our study was aimed at evaluating the reliability of oesophageal pulse oximetry in major burns patients. Seven adult patients (five males, two females) were studied. They were sedated and ventilated as part of their routine care. Measurable photoplethysmographic (PPG) traces and SpO(2) values were obtained in the oesophagus of all patients at a mean depth of 15.6+/-1.8 cm (measured from the lips). It was found that the oesophageal pulse oximeter results were in good agreement with oxygen saturation measurements obtained by a CO-oximeter. The mean (+/-S.D.) of the differences between the oesophageal oxygen saturation results and those from CO-oximetry was 0.50+/-0.69%. A Bland and Altman analysis showed that the bias and the limits of agreement between the oesophageal and commercial toe pulse oximeters were 0.4% and -3.6% to 4.6%, respectively. This study suggests that the oesophagus can be used as an alternative site for monitoring arterial blood oxygen saturation by pulse oximetry in burned patients.

Estimation of instantaneous venous blood saturation using the photoplethysmograph waveform.

Non-invasive estimation of regional venous saturation (SxvO2) using a conventional pulse oximeter could provide a means of obtaining clinically relevant information. This study was carried out in order to investigate the hypothesis that SxvO2 could be estimated by utilising the modulations created by positive pressure ventilation in the photoplethysmograph (PPG) signals. The modulations caused by the mechanical ventilator were extracted from oesophageal PPG signals obtained from 12 patients undergoing cardiothoracic surgery. The signals analysed in this work were acquired in a previous study. For the purpose of this analysis the raw PPG signal was considered to have three major components, ac PPG signal (cardiac related component), a static component or dc PPG signal (created mostly by the absorption of light by surrounding tissue) and the ventilator modulation component. These components were then used to estimate instantaneous arterial blood oxygen saturation (SpO2) and SxvO2 by utilising time-frequency analysis technique of smoothed-pseudo Wigner-Ville distribution (SPWVD). The results showed that there was no significant difference in the traditionally-derived (time-domain) arterial saturation and the instantaneous arterial saturation. However, the instantaneous venous saturation was found to be significantly lower than the estimated time-domain and instantaneous arterial saturation (P = < 0.001, n = 12).

Randomized placebo-controlled trial of the activity of the morphine glucuronides.

BACKGROUND: Morphine-6-glucuronide (M6G) is an active metabolite of morphine with potent analgesic activity. Morphine-3-glucuronide (M3G), the most prevalent metabolite, has minimal affinity for opioid receptors. It has been suggested from animal model data and by examination of metabolite ratios in humans that M3G may functionally antagonize the respiratory depressant and analgesic actions of morphine and M6G. METHODS: We performed a double-blind placebo-controlled trial with 10 healthy volunteers. The trial had 6 arms: (1) placebo, (2) 10 mg/70 kg of morphine, (3) 3.3 mg/70 kg of M6G, (4) 30.6 mg/70 kg of M3G, (5) 30.6 mg/70 kg of M3G with 10 mg/70 kg of morphine, and (6) 30.6 mg/70 kg of M3G with 3.3 mg/70 kg of M6G; all were give by slow intravenous bolus. Analgesia was assessed with the use of the submaximal ischemic pain model. The effects were quantified on numerical and visual analogue scales. Respiratory parameters and response to steady state 5% carbon dioxide challenge were assessed with spirometry, mass spectroscopy, and earlobe blood gas analysis. RESULTS: Morphine and M6G produced significant pain relief compared with placebo (morphine, P < .0001; M6G, P = .033). Pain relief after M6G was less than after morphine (P = .009) and M3G was no better than placebo (P = .26). Pain relief with morphine and M6G were not significantly altered by M3G (P = .59 and P = .28, respectively). Significant and similar dysphoria and sedation occurred with both morphine (P < .002) and M6G (P < .016) but were absent with both M3G and placebo. Respiratory parameters suggested that M6G produced less respiratory depression than morphine. Both morphine and M6G caused a significant reduction in respiratory drive compared with placebo (morphine, P = .002; M6G, P = .013); this effect was not reversed by M3G (P = .35 and P = .83, respectively). CONCLUSIONS: M3G appears to be devoid of significant activity; in these circumstances and at these doses, it does not antagonize either the analgesic or respiratory depressant effects of M6G or morphine.

A simple, rapid and sensitive semimicro method for the measurement of cyanide in blood.

Conventional methods do not meet the clinical need for rapid cyanide measurements. We report a procedure which can provide a result in 10 min. It should be of particular interest to laboratories serving cardiac or renal units which use the hypotensive agent sodium nitroprusside, and burns units to which fire victims may be admitted suffering the effects of HCN from inhaled smoke. A sample of blood (100 microL) is mixed with H3PO4, containing a surfactant, and the HCN is trapped in an alkaline mixture of 1,2-dinitrobenzene and 4-nitrobenzaldehyde in 2-methoxyethanol. The catalytic action of cyanide, which produces purple 2-nitrophenylhydroxylamine, is stopped with acetone after 6 min. The absorbance measured at 560 nm shows a linear relationship with the cyanide concentration, but the slope varies with the ambient temperature. Since KCN added to both 50 mmol/L NaOH and blood gives similar assay results, any inaccuracy arising from changes in temperature can be avoided by running standards at the same time as the blood sample.