Emergency interventions for hyperkalaemia.

BACKGROUND: Hyperkalaemia occurs in outpatients and in between 1% and 10% of hospitalised patients. When severe, consequences include arrhythmia and death. OBJECTIVES: To review randomised evidence informing the emergency (i.e. acute, rather than chronic) management of hyperkalaemia SEARCH STRATEGY: We searched MEDLINE (1966-2003), EMBASE (1980-2003), The Cochrane Library (issue 4, 2003), and SciSearch using the text words hyperkal* or hyperpotass* (* indicates truncation). We also searched selected journals and abstracts of meetings. The reference lists of recent review articles, textbooks, and relevant papers were reviewed for additional potentially relevant titles. SELECTION CRITERIA: All selection was performed in duplicate. Articles were considered relevant if they were randomised, quasi-randomised or cross-over randomised studies of pharmacological or other interventions to treat non-neonatal humans with hyperkalaemia, reporting on clinically-important outcomes, or serum potassium levels within the first six hours of administration. DATA COLLECTION AND ANALYSIS: All data extraction was performed in duplicate. We extracted quality information, and details of the patient population, intervention, baseline and follow-up potassium values. We extracted information about arrhythmias, mortality and adverse effects. Where possible, meta-analysis was performed using random effects models. MAIN RESULTS: None of the studies of clinically-relevant hyperkalaemia reported mortality or cardiac arrhythmias. Reports focussed on serum potassium levels. Many studies were small, and not all intervention groups had sufficient data for meta-analysis to be performed. On the basis of small studies, inhaled beta-agonists, nebulised beta-agonists, and intravenous (IV) insulin-and-glucose were all effective, and the combination of nebulised beta agonists with IV insulin-and-glucose was more effective than either alone. Dialysis is effective. Results were equivocal for IV bicarbonate. K-absorbing resin was not effective by four hours, and longer follow up data on this intervention were not available from RCTs. AUTHORS' CONCLUSIONS: Nebulised or inhaled salbutamol, or IV insulin-and-glucose are the first-line therapies for the management of emergency hyperkalaemia that are best supported by the evidence. Their combination may be more effective than either alone, and should be considered when hyperkalaemia is severe. When arrhythmias are present, a wealth of anecdotal and animal data suggests that IV calcium is effective in treating arrhythmia. Further studies of the optimal use of combination treatments and of the adverse effects of treatments are needed.

The first fatal 2,6-di-isopropylphenol (propofol) poisoning in Singapore: a case report.

The propofol levels in the blood and tissues of a 37-year-old Chinese male suspected of having fatally self-administered an intravenous dose of 1600 mg of propofol (12.3-15.4 times the dose required for the induction of anaesthesia) were determined by headspace gas chromatography. The blood (femoral), liver, kidney and brain propofol levels were 2.5 micrograms/ml, 22 micrograms/g, 3.6 micrograms/g and 11.3 micrograms/g, respectively. The blood propofol level in the present case is 11.4 times and the liver propofol level is 15.7 times that of the first propofol overdose reported in the literature.

Toxicological screen on gastric aspirates: the Singapore experience.

In the early eighties, in response to increasing self-poisoning incidents by pharmaceuticals in Singapore, a comprehensive wide-sweep screen for these drugs in clinical gastric aspirates was devised and implemented by us. The toxicological screen which involved quadruplicate extractions, two in acidic conditions and the other two in alkaline conditions, required the following analyses to be carried out: UV on the acidic fraction, TLC on the basic fraction and mega-bore capillary GC/NPD (nitrogen phosphorus detector) on the combined fraction. The combined fraction if necessary was subjected to GC/MS analysis. Our screen satisfied the need to confirm the analytical outcome of one method by another. Combining the acidic and basic fractions for a single GC analysis saves on instrument time and manpower. All coma and emergency cases were required to undergo GC/MS analysis to prove the identity of toxic agents beyond reasonable doubt. Quality control procedures were instituted at key steps to ensure quality of analytical outcome.

Acidic and neutral drugs screen in blood with quantitation using microbore high-performance liquid chromatography-diode array detection and capillary gas chromatography-flame ionization detection.

Blood previously acidified with aqueous saturated ammonium chloride solution was extracted with ethyl acetate. The dried extract was subjected to acetonitrile-hexane partition. The acetonitrile portion was analysed for the presence of acidic and neutral drugs by HPLC-DAD (200 mm x 2.1 mm I.D. microbore ODS-Hypersil column) and GC-FID (25 m narrow-bore x 0.25 mm I.D. HP-5 column with 0.33 micron film thickness). The protocol was found to be suitable for both clinical toxicology (including emergency toxicology) and postmortem toxicology. At least 66 drugs of interest were unequivocally identified by RRTs (HPLC) and UV spectra (DAD) match while another 12 were unequivocally identified by double RRTs match (HPLC and GC). Quantitation was facilitated by incorporating calibration blood standards in each assay batch. The five drugs most commonly encountered in clinical blood specimens (1150 cases) were: paracetamol (47.4% of the cases); chlormezanone (6.6%), theophylline (1.74%), naproxen (1.65%) and mefenamic acid (1.56%). The following drugs were detected in toxicologically significant quantities in postmortem blood specimens (245 cases): phenobarbitone (1.22% of the cases), naproxen (0.82%), chlormezanone (0.82%), theophylline (0.82%), carbamazepine (0.41%) and paracetamol (0.41%).

Ammonia gassing deaths--a report on two cases.

The gross postmortem features of two victims (a 17-year-old and a 33-year-old male, both of Chinese descent) who died shortly after an ammonia-gassing exposure, are presented. The findings of extensive thermal burns on the body surfaces and on the lips, conjunctivitis and opaque cornea on both eyes, oedematous and congested lungs with large areas of haemorrhages, etc, were consistent with injuries inflicted by a corrosive gas such as ammonia. The postmortem toxicological findings of elevated blood ammonia levels supported the postmortem findings. The pulmonary and femoral blood ammonia levels (0.26 mg/mL and 0.65 mg/mL) of decedent one were at least 371 times and 928 times respectively higher than normal. Similarly, the pulmonary and femoral blood ammonia levels (0.51 mg/mL and 0.43 mg/mL) of decedent two were at least 728 times and 614 times respectively higher than normal.

Normal boron excretion levels and borates related gastroenteritis cases in Singapore.

Urinary borates calculated as boric acid were found to span 0 to 54 microgramme per ml urine for both Singaporean adults (population size: 507) and children (population size: 162). The normal dietary boron intake could account for the urinary boric acid levels observed. Of the hundred and fifty-three children who suffered from gastroenteritis in Singapore over the period from Jan to May 1989, two were found to have urinary boric acid exceeding 54 micrograms per ml urine. One of them was said to have consumed fish balls, bean curds and noodles prior to the onset of illness. These food items were among those likely to have added borates. Unfortunately, the dietary intake prior to the onset of illness of the other child was not recorded. Of the hundred and twelve adults affected by gastroenteritis in Dec 1988 in the Tiong Bahru area, one was found to have boric acid level of 117 micrograms per ml urine, indicative of added borates in the diet. The present study showed that borates related gastroenteritis incidents in Singapore over the time-period of our study at least, were few and far in between. With the on-going surveillance for the presence of added borates in both locally manufactured and imported food and the continued tight control over the importation and sale of borates, future incidents are likely to be minimal.

Blood aflatoxin levels in patients with hepatocellular carcinoma in Singapore.

Aflatoxin (AF), a highly potent hepatocarcinogen, is strongly implicated in the pathogenesis of human hepatocellular carcinoma (HCC). In this study, our aim was to determine if this carcinogen is associated with cases of HCC in Singapore. Blood levels of the naturally-occurring AFs--B1, B2, G1 and G2--were assayed in 56 cases of HCC. AF was detected in only 2/56 (3.6%) cases of HCC, one each of AF-B1 and AF-G1. In contrast, in a similar survey done in Singapore on normal subjects, AF was positive in 64/423 (15.1%) cases. The low frequency of AF detection in our patients suggests that HCC in Singapore is not associated with significant chronic exposure to AF.

Toxicology Services in Singapore.

The toxicology laboratory provides a whole range of forensic toxicology services to the doctors, pathologists, law enforcement agencies and the public. This paper, anchored in one hundred and ten years of history, traces the practice and development of this laboratory to the present day of offering services in blood for alcohol determinations, antemortem biological fluids (gastric aspirate, blood, etc.) and postmortem biological fluids and tissues (liver, kidney, etc.) for drugs and poisons screen. This paper spells out in detail the nature of specimens required, the analytical techniques used, the toxins looked for and the medico-legal implications of our analytical findings. A number of recent cases of interest are presented.

Poppy seeds: implications of consumption.

Three white poppy seed samples of Papaver somniferum L were found to contain total morphine (free and bound) in the range 58.4 to 62.2 micrograms/g seeds and total codeine (free and bound) in the range 28.4 to 54.1 micrograms/g seeds. Soaking seeds in water was found to remove 45.6 per cent of the free morphine and 48.4 per cent of the free codeine. In ingesting a curry meal or two containing various amounts of washed seeds (morphine intake: 200.4 to 1002 micrograms; codeine intake: 95.9 to 479.5 micrograms), the urinary morphine levels were found to be in the range 0.12 to 1.27 micrograms/ml urine and urinary codeine levels in the range 0.04 to 0.73 micrograms/ml urine. In any large scale screening for abuse of opiate drugs, the possibility of urinary alkaloids arising from consuming food containing poppy seeds must be considered and, if possible, eliminated.

Common poisons in Singapore--past and present.

A study on past toxicological activities in Singapore enabled us to capture the trends of poisons abused in this country over the last 108 years. Until the early sixties, corrosive alkali and acids, alcohol (poisoning cases), inorganic chemicals, heavy metals and plant alkaloids were the mainstay of poisons principally used. The seventies and eighties saw a swing towards pharmaceuticals. The 1988-89 data gave alcohol (poisoning cases), pharmaceuticals, household items such as detergents, hypochlorite and antiseptic, carbon monoxide, paraquat, malathion, organic solvents (toluene and xylenes) and narcotics as the mainstay of poisons encountered. The last two classes of poisons reflect the continuing problems of glue sniffing and narcotics abuse facing Singapore.

Glue sniffing deaths in Singapore--volatile aromatic hydrocarbons in post-mortem blood by headspace gas chromatography.

Over a period from 1983 to 1991, of a total of 19,000 post-mortems, 33 were found to have at least one aromatic hydrocarbon (benzene, toluene or xylenes) in the blood. Of the 33 deceased, 22 had a history of toluene or petrol abuse while most of the remaining 11 were suspected to be glue sniffers through evidence found at the scene. This number, which represented 0.17 per cent of all the unnatural deaths, is considered small for a nation having a glue sniffing epidemic. The low death rate, as compared to 2.1 per cent through drug and chemical poisoning during the same period, is attributed to the timely intervention by the Government who outlawed glue sniffing and the effectiveness of compulsory rehabilitation. The male gender predominates (81.8 per cent) among the 33 deceased with a mean age of 20.1 years (range 15 to 33). The mean age for the female gender is 17.7 years (range 16 to 20). The blood toluene levels were found to be in the range 0.2 to 92 micrograms per ml blood. The causes of death are: 63.6 per cent due to falling or suicide by jumping; 18.2 per cent drowning; 6.1 per cent hanging; 6.1 per cent homicide; and 6.1 per cent acute toluene poisoning. The high proportion of traumatic deaths are discussed. Headspace gas chromatography with a suitable GC column was used for the analysis. Calibration blood standards were prepared in situ or in bulk stabilized by 10 per cent (v/v) methanol to overcome the hydrophobic and volatile nature of the aromatic hydrocarbons.(ABSTRACT TRUNCATED AT 250 WORDS)

Aflatoxin exposure in Singapore: blood aflatoxin levels in normal subjects, hepatitis B virus carriers and primary hepatocellular carcinoma patients.

Blood screening conducted on Singaporeans over 1991-1992 showed exposure to predominantly aflatoxin B1 and to a lesser extent G1. The extent of exposure to B1 among three groups of residents in Singapore, namely normal subjects (n = 423), hepatitis B virus carriers (n = 302) and primary hepatocellular carcinoma (PHC) patients (n = 58) were extensive as reflected by the positive rates of 15.1, 0.7 and 1.7 per cent respectively. However, the degree of individual exposure to this toxin among the three groups was considered low as shown by the low respective mean blood levels of 5.4 +/- 3.2 (range 3.0-17), 7.7 (range 7.5-7.9) and 7.5 picogrammes per ml of blood. It is not immediately clear whether or not such low levels would precipitate an undesirable health effect. The higher positive rate seen in normal subjects as compared with the other groups could be due to differences in dietary intake of aflatoxin B1, differences in metabolic patterns or both. About 70 per cent of PHC patients studied were carriers. The degree of aflatoxin B1 exposure among normal subjects in Singapore was a factor of 22.1 times less than that in Japan, 40.9 times less than that in Indonesia and 51.3 times less than that in the Philippines. Similarly, the extent of exposure among hepatitis B carriers in Singapore was a factor of 8.2 times, 39.6 times and 24.2 times less than those in the other three Asiatic countries respectively. The results reflected stringent Government control over the quality of food stuff imported into this country. As Singapore imports almost all of its dietary needs from elsewhere, it can afford to be selective at a cost. Aflatoxin M1, a metabolite of B1, was most commonly encountered in the liver tissues of deceased (n = 154) who died of causes other than sickness or disease in 1992-93, consistent with our blood findings of prevalence of aflatoxin B1. High performance liquid chromatography (HPLC) with fluorescence detection using one of the aflatoxins G2 or B2 as an internal standard was used for the detection and quantification of aflatoxins. The use of an internal standard structurally and chemically similar to those required to be quantified minimizes errors in quantifications. This is because differences in the quenching of fluorescence between specimen extracts and spiked-standard extracts were internally standardized and compensated for. The presence of an internal standard also helped to locate aflatoxins of interest more accurately.(ABSTRACT TRUNCATED AT 400 WORDS)

Photochromic salicylideneaniline as storage medium for interferometry and high speed recording.

Sample fabrication technique and characteristics of salicylideneaniline photochromic material and its applications as a temporary data storage medium in real-time holographic interferometry and high speed data recording are presented.

Relationship between postmortem blood and vitreous humor ethanol levels.

The relationship between the blood to vitreous humor ethanol ratios (B/V) and the corresponding urine to blood ethanol ratios (U/B) of 200 postmortem cases were found to be bimodal in nature. Using the U/B ratio of 1.20 as a demarcation below which early absorption prevails, the results in the early absorption phase gave an average B/V ratio of 1.29, a range from 0.71 to 3.71, and a relatively large standard deviation of 0.57, whereas the results in the other phases (late absorption and elimination) gave an average B/V ratio of 0.89, a spread from 0.32 to 1.28, and a standard deviation of 0.19. It would appear that the blood ethanol levels can be estimated using B = 1.29 V for early absorption phase cases and B = 0.89 V for cases in subsequent phases. The former relationship would underestimate the blood ethanol levels in cases of very early absorption phase and the later overestimate the levels of late elimination cases. The ethanol distribution results in cases of fatal road traffic accidents and suicides by falling, in which 69% of the deceased sustained some form of head injury, were found to be similar to those of other postmortem cases. The observations reflect that vitreous humor, being reasonably protected, is likely to survive certain traumatic deaths and be available for postmortem ethanol investigation. The U/B ethanol ratios recorded in this work had an average of 1.29, a range from 0.19 to 5.19, and a standard deviation of 0.48.

Critical assessment of four monoclonal antibodies reactive with B-cells in formalin-fixed paraffin-embedded tissues.

Four commercially available monoclonal antibodies, MB1, MB2, LN1 and LN2, were studied to determine their sensitivity and specificity for the diagnosis of B-cell lymphomas when used on formalin-fixed paraffin-embedded tissues. In addition to 125 cases of immunologically characterized non-Hodgkin's lymphoma, a range of normal tissues, reactive lymphoid proliferations, Hodgkin's disease and granulocytic sarcomas were also studied. MB1 was found to give positive results in 53.6% of B-cell lymphomas, but the staining was sometimes weak and patchy; there was also cross-reaction with 1.8% of T-cell lymphomas. MB2 reacted with 88.4% of B-cell lymphomas and the reaction was often strong and diffuse, but it showed cross-reaction with 18.2% of T-cell lymphomas. LN1 and LN2 gave positive staining of 44.9 and 46.4% of B-cell lymphomas respectively, and the results appeared to be inferior to that obtained in B5-fixed tissues; staining was sometimes weak and focal, and they also gave false-positive results in a few cases of T-cell lymphoma. This study shows that MB1, LN1 and LN2 are fairly but not entirely specific for B-cells in the non-Hodgkin's lymphomas, but are not very sensitive when applied to formalin-fixed tissues. MB2 shows a high sensitivity but only moderate specificity. Therefore, when these antibodies are used to determine the immunophenotype of malignant lymphomas, the B-cell nature can be predicted with great confidence only when two, preferably three or more, of the antibodies give positive results. The potential applications of these antibodies are discussed.

Drinking and driving in Singapore, 1987 to 1989.

Between 1987 and 1989 there were approximately 5,000 cases of fatal and injury-sustained road traffic accidents, of which 2.3-3.0% were alcohol related (blood alcohol levels greater than the legal limit of 80 mg% ethanol). The offenders of alcohol-related accidents are mostly Chinese (> 79%), male (> 98%), and more often 30-40 years old. The majority of the alcohol-related accidents (> 74%) took place between 8 P.M. and 4 A.M. in fine weather and light traffic. Rear-end, head-on, and side-on collisions comprised > 60% of all the alcohol-related accidents, and losing control of vehicles approximately 30%. Drunken driving cases for the same period that were not accidents showed a number of characteristics similar to those for accidents. In Singapore, motorcycle riders and pedestrians are more prone to road fatality than other road-user groups. International comparisons of road fatalities per 100,000 population gave Singapore one of the lowest accident rates (8.1-8.4) as compared with countries such as Australia, the United Kingdom, the United States, New Zealand, Canada, and Japan.

Drinking and driving in Singapore 1987 to 1989.

In the period 1987 to 1989 there were about 5,000 cases of fatal and injury-sustained road traffic accidents, of which 2.3 to 3.0% were alcohol-related (Blood alcohol levels greater than the legal limit of 80 mg % ethanol). The offenders of alcohol-related accidents are mostly Chinese (greater than 79%), predominantly of the male gender (greater than 98%), and more often than not in the 30 to 40 age-range. The majority of the alcohol-related accidents took place between 8 p.m. to 4 a.m. (greater than 74%) under fine weather and light traffic. Rear-end, head-on and side-on collisions comprised over 60% of all the alcohol-related accidents and losing control of vehicles about 30%. Drunken driving non-accident cases for the same period showed a number of characteristics similar to those for alcohol-related accident cases. In Singapore motorcycle riders and pedestrians are more prone to road fatality than other road-user groups. International comparisons of road fatalities per 100,000 population gave Singapore one of the lowest accident rates (8.1 to 8.4) as compared to countries such as Australia, the United Kingdom, the United States, New Zealand, Canada and Japan.

Gas chromatographic study of the urinary codeine-to-morphine ratios in controlled codeine consumption and in mass screening for opiate drugs.

The urinary codeine-to-morphine ratios in fifteen volunteers administered codeine tablets at intervals were studied by gas chromatography (GC) and compared with one month's GC results for enzyme multiplied immunoassay technique (EMIT)-screened urine specimens in a mass-screening programme for abuse of opiate drugs, particularly heroin. It appears that when M less than 2 and C/M greater than 0 or when M greater than 2 and C/M greater than 0.5, where C and M are codeine and morphine concentrations in micrograms per 10 ml of urine, codeine consumption has to be presumed.