Toxicology

Editorial Hyperbaric oxygen for carbon monoxide poisoning Are currently recommended regimens ineffective? MJA 1999; 170: 197-199 In 1950 Pace and colleagues published a report establishing that hyperbaric oxygen (HBO) significantly accelerates the rate of carbon monoxide (CO) elimination from haemoglobin.1 Further studies have shown that, after CO exposure, HBO accelerates the dissociation of CO from cytochrome a,a3 and induces a more rapid return to normal of cytochrome redox state,2,3 reduces brain lipid peroxidation,4 inhibits pathological endothelial leukocyte adhesion5 and prevents intracranial hypertension.6It has therefore been no surprise that clinical observation and published evidence, including that of randomised trials, have supported the clinical efficacy of HBO for CO poisoning.7-12 When HBO is given to individuals with moderate or severe poisoning within approximately six hours of exposure, most published data strongly suggest that it not only induces a more rapid recovery, but also reduces the most-feared complication -- persistent or delayed neurological sequelae. Nevertheless, questions remain. As HBO therapy is not immediately available to all poisoned patients, who should be treated or transported to a hyperbaric facility? How many treatments should be given? There have been few randomised trials of HBO therapy, and no published randomised trial has addressed the question of whether it is effective in the treatment of severely poisoned patients. Therefore, a large trial from a reputable institution is welcome. In this issue of the Journal, Scheinkestel and colleagues13 have addressed the question of whether HBO should be used for CO poisoning. Their study design is among the most rigorous yet published in this area. Nonetheless, methodological questions remain, and some caution is required in accepting the authors' conclusions. In the study, all 191 patients were treated for 100 minutes in a hyperbaric chamber, but were randomised to receive either normobaric oxygen (NBO) or HBO at 2.8 atmospheres absolute (ATA) for 60 of the 100 minutes. All patients received continuous high flow oxygen between treatments, or 100% oxygen if they were intubated. They received one treatment per day for three days, after which they underwent neuropsychological assessment. If, after this, they had clinical or neuropsychological abnormalities, they received an additional three treatments. Most patients in this study were poisoned during an attempted suicide, and 73% were categorised as severe (defined by a carboxyhaemoglobin level >30%, Mini-mental score ≤24, confusion, loss of consciousness, focal neurological deficits, convulsions, pulmonary oedema, electrocardiogram abnormalities or dysrhythmias, hypotension, cardiac arrest or acidosis). Nevertheless, inclusion of mildly poisoned patients and the high average Mini-mental scores suggest that a significant number of patients had only mild central nervous system impairment at the time of presentation. The use of cluster randomisation for patients presenting simultaneously (to minimise the effect of the study on daily practice) engenders the risk of bias, as clusters of patients with similar baseline characteristics are simultaneously assigned to one or other of the groups. Generalised linear models were used to adjust for within-cluster correlation, but the authors have not provided enough information to allow an assessment as to whether the statistical analysis accounted for all of the resulting bias. A confirmatory analysis that would not have incurred this potential bias would have been a reanalysis of the results using only one patient from each cluster. This might have strengthened the report, as would a display of the numbers and sizes of clusters and a listing of the magnitude and consistency of the parameter estimates for the various models. The primary results of the study depend heavily on seven neuropsychological assessments that were performed after treatment and before discharge. Two or more "abnormal" test results represented a poor outcome, which then defined persistent neurological sequelae (PNS). Conclusions based on these tests must be tempered by the fact that, although baseline Mini-mental state tests were done, the study did not make baseline neuropsychological assessments, and hence could not quantify change for these patients. The only statistically significant difference between NBO and HBO patients at the end of treatment was in one of seven neuropsychological scales (Rey auditory verbal learning test), which favoured patients treated with NBO. Considering the multitude of statistical tests performed and the lack of a comprehensive baseline assessment, a single significant test may not be meaningful. In view of the weight of evidence in favour of the use of HBO for acute CO poisoning, how can the conclusions of Scheinkestel and colleagues that there is no difference in efficacy between HBO and NBO be explained? Firstly, it is possible that their method of NBO administration was more effective than in other studies. All their patients received three or six days of high-flow oxygen, and intubated patients might have been given 100% oxygen for six continuous days, a regimen that is considerably more intensive than common clinical practice. Secondly, their HBO regimen may have appeared less effective than in other studies, for several reasons. Depression can confound neuropsychological assessment, and the high proportion of depressed patients in the study may have minimised the apparent effect of HBO treatment and contributed to the high number of patients with a poor outcome. Unfortunately, neither the inspired oxygen concentration in either group nor the exact pressure-time profile of the hyperbaric treatments is provided. However, adding up to six HBO sessions to 100% oxygen for three or six days would be expected to produce a significant degree of pulmonary oxygen toxicity. Also, as Scheinkestel and colleagues point out, repetitive treatments at 2.8 ATA (a pressure higher than many clinicians use for CO poisoning) might have induced a neurotoxic effect14 that offset any potential benefit. Further, there are significant omissions from the article that preclude unfettered acceptance of the authors' conclusions. The surprising observation that there was no significant improvement in Mini-mental score in either group is weakened by the lack of information regarding administration of sedative drugs, especially to intubated patients, which might have confounded the testing. Importantly, other than mortality, no clinical outcomes or self-reported assessments of functional ability are reported. The overall relapse rate at follow-up, defined as new morbidity or deterioration in any neuropsychological test score, was higher in the group treated with HBO, but the relapse rate in the various subgroups of greatest interest (particularly those with short treatment delays) is not detailed. Moreover, the low follow-up rate (46%) makes it difficult to draw valid conclusions. The data regarding comparability of the two groups have two significant omissions -- the numbers of severely affected patients with long delays to treatment, and the number of mildly affected patients. Neither of these subgroups is likely to show a measurable response to treatment using the chosen endpoints. The possibility that both types were significantly represented is suggested by Mini-mental scores that appear disproportionately high for the degree of severity that is implied, as well as the high geometric mean of the delays to treatment (>6 hours). It therefore appears possible that a significant proportion of the patients in this study were treated at a time after CO exposure that HBO is likely to be ineffective.15-17 Including a large number of patients who are unlikely to respond (too mildly affected or treated too late) in a study will reduce the apparent effectiveness of the intervention, and might partly explain the surprisingly high proportion of patients with PNS (74% and 68% of patients, respectively, in the HBO and NBO groups). What might otherwise have been the most important conclusion of this investigation -- that even in the subgroup of severe poisonings treated within four hours, there was no difference between NBO and HBO -- would have been more convincing had the authors provided the observational and statistical details. What new information can be learned from the work of Scheinkestel and colleagues? Their results hint that, in the type of patients studied, prolonged administration of NBO may be more effective than the shorter regimens that are in general use. With respect to the primary question addressed by the investigators,13 we feel that there are still too many unresolved issues in their analysis to discard HBO as a treatment for acute CO poisoning. Richard E Moon Professor of Anesthesiology, and Associate Professor of Pulmonary and Critical Care Medicine Elizabeth DeLong Associate Professor, Division of Biometry Duke University Medical Center, Durham, NC, USA Pace N, Strajman E, Walker E. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652-654. Brown SD, Piantadosi CA. Reversal of carbon monoxide-cytochrome c oxidase binding by hyperbaric oxygen in vivo. Adv Exp Med Biol 1989; 248: 747-754. Brown SD, Piantadosi CA. Recovery of energy metabolism in rat brain after carbon monoxide hypoxia. J Clin Invest 1992; 89: 666-672. Thom S. Antagonism of carbon monoxide-mediated brain lipid peroxidation by hyperbaric oxygen. Toxicol Appl Pharmacol 1990; 105: 340-344. Thom SR. Functional inhibition of leukocyte 2 integrins by hyperbaric oxygen in carbon monoxide-mediated brain injury in rats. Toxicol Appl Pharmacol 1993; 123: 248-256. Jiang J, Tysseborn I. Cerebrospinal fluid pressure changes after acute carbon monoxide poisoning and therapeutic effects of normobaric and hyperbaric oxygen in conscious rats. Undersea Hyperb Med 1997; 24: 245-254. Myers RAM, Snyder SK, Emhoff TA. Subacute sequelae of carbon monoxide poisoning. Ann Emerg Med 1985; 14: 1163-1167. Norkool DM, Kirkpatrick JN. Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: a review of 115 cases. Ann Emerg Med 1985; 14: 1168-1171. Gorman DF, Clayton D, Gilligan JE, Webb RK. A longitudinal study of 100 consecutive admissions for carbon monoxide poisoning to the Royal Adelaide Hospital. Anaesth Intensive Care 1992; 20: 311-316. Ducasse JL, Celsis P, Marc-Vergnes JP. Non-comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation? Undersea Hyperbar Med 1995; 22: 9-15. Thom S, Taber R, Mendiguren I, et al. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25: 474-480. Hampson NB. Carbon monoxide poisoning in the United States. In: Oriani G, Marroni A, Wattel F, editors. Handbook on hyperbaric medicine. New York: Springer, 1996: 297-304. Scheinkestel CD, Bailey M, Myles PS, et al. Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial. Med J Aust 1999; 170: 203-210. Holbach KH, Caroli A, Wassmann H. Cerebral energy metabolism in patients with brain lesions at normo- and hyperbaric oxygen pressures. J Neurol 1977; 217: 17-30. Zanetti CL. A review of carbon monoxide poisoning treated at Edgewater Hospital. In: Kindwall EP, editor. Proceedings of the Eighth International Congress on Hyperbaric Medicine. 1984; Aug 20-22; Long Beach, CA. San Pedro, CA: Best Publishing, 1987: 258-262. Goulon M, Barois A, Rapin M, et al. Carbon monoxide poisoning and acute anoxia due to breathing coal gas and hydrocarbons. J Hyperbaric Med 1986; 1: 23-41. Raphael JC, Elkharrat D, Jars-Guincestre MC, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet 1989; 2: 414-419. 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Research Hyperbaric or normobaric oxygen for acute carbon monoxide poisoning: a randomised controlled clinical trial Carlos D Scheinkestel, Michael Bailey, Paul S Myles, Kerry Jones, D James Cooper, Ian L Millar and David V Tuxen MJA 1999; 170: 203-210 For editorial comment, see Moon & DeLong Abstract - Introduction - Methods - Results - Discussion - Conclusion - References - Authors' details - - More articles on Anaesthesia and intensive care Abstract Objective: To assess neurological sequelae in patients with all grades of carbon monoxide (CO) poisoning after treatment with hyperbaric oxygen (HBO) and normobaric oxygen (NBO). Design: Randomised controlled double-blind trial, including an extended series of neuropsychological tests and sham treatments in a multiplace hyperbaric chamber for patients treated with NBO. Setting: The multiplace hyperbaric chamber at the Alfred Hospital, a university-attached quarternary referral centre in Melbourne providing the only hyperbaric service in the State of Victoria. Patients: All patients referred with CO poisoning between 1 September 1993 and 30 December 1995, irrespective of severity of poisoning. Pregnant women, children, burns victims and those refusing consent were excluded. Intervention: Daily 100-minute treatments with 100% oxygen in a hyperbaric chamber -- 60 minutes at 2.8 atmospheres absolute for the HBO group and at 1.0 atmosphere absolute for the NBO group -- for three days (or for six days for patients who were clinically abnormal or had poor neuropsychological outcome after three treatments). Both groups received continuous high flow oxygen between treatments. Main outcome measures: Neuropsychological performance at completion of treatment, and at one month where possible. Results: More patients in the HBO group required additional treatments (28% v. 15%, P = 0.01 for all patients; 35% v. 13%, P = 0.001 for severely poisoned patients). HBO patients had a worse outcome in the learning test at completion of treatment (P = 0.01 for all patients; P = 0.005 for severely poisoned patients) and a greater number of abnormal test results at completion of treatment (P = 0.02 for all patients; P = 0.008 for severely poisoned patients). A greater percentage of severely poisoned patients in the HBO group had a poor outcome at completion of treatment (P = 0.03). Delayed neurological sequelae were restricted to HBO patients (P = 0.03). No outcome measure was worse in the NBO group. Conclusion: In this trial, in which both groups received high doses of oxygen, HBO therapy did not benefit, and may have worsened, the outcome. We cannot recommend its use in CO poisoning. Introduction Carbon monoxide (CO) poisoning is one of the most common lethal poisonings,1 with neurological or psychiatric sequelae occurring in up to 67% of survivors.2Treatment with hyperbaric oxygen (HBO) is recommended because it reduces carboxyhaemoglobin (COHb) dissociation half-life from more than four hours at room air or 45 minutes on 100% oxygen to 23 minutes at 2.5 atmospheres absolute (ATA).3 Carbon monoxide also inhibits cellular respiration by binding to cytochrome oxidase, a component of the mitochondrial electron transport chain.4 Hyperbaric oxygen enhances the dissociation of CO from this enzyme.5 Despite these physiological effects, it has not been established in humans that HBO either improves survival or decreases neuropsychological deficits. Much of the evidence that HBO is more efficacious than normobaric oxygen (NBO) therapy in humans arises from isolated case reports,6-8 uncontrolled clinical observations,9-11 small,12 non-randomised13 and unblinded series9,11,13-20 and incomplete assessment of outcome (no neuropsychological testing).9,11,15-18 All reported non-randomised studies have suggested benefit from HBO. Of the four published randomised studies, two report benefit from HBO12,14 and two report no benefit15,17 (Box 1). Three restricted entry to mildly poisoned patients, while the fourth15 included severely poisoned patients, but did not allocate any to NBO treatment. None of the randomised studies blinded patients by using sham treatments for NBO, only one blinded outcome assessment12 and only one used neuropsychological tests to assess outcome.14 Hence, the benefit of HBO in CO poisoning has been questioned1,2,21-27 and remains unproven. We therefore performed a randomised double-blind trial in patients with all grades of CO poisoning, comparing HBO and NBO (with sham treatments for the NBO group), and using an extended series of neuropsychological tests to assess both persistent and delayed neurological sequelae (PNS and DNS). Methods The multiplace chamber at the Alfred Hospital, a university-attached quarternary referral centre, provides the only hyperbaric service in the State of Victoria (population, 4.5 million; area, 228 000 km2). Between 1 September 1993 and 30 December 1995, most CO-poisoned and all severely poisoned patients were referred for treatment. We included all referred patients, irrespective of severity of poisoning. Patients were excluded if they were pregnant, children, burns victims or if they did not consent. Informed consent to enter the trial was requested from patients with a Mini-mental score >2428 and from the next of kin for those obtunded or with a score ≤24. The Alfred Hospital's Ethics Committee approved the trial, conditional on an independent blinded interim analysis after recruitment of 50 patients (using a stopping rule of P < 0.001); this allowed continuation of enrolment to completion. Randomisation and blinding Patients were randomly allocated to HBO or NBO treatment. To ensure a similar distribution of causes and severity of poisoning in both groups, patients were first stratified into four groups (suicide versus accidental, then mechanically ventilated versus non-ventilated). A hyperbaric technician then allocated patients to treatment groups by opening envelopes chosen from random blocks, each with equal numbers of HBO and NBO selections. To minimise the impact of the trial on daily practice, we used cluster randomisation for patients who presented simultaneously from the same CO exposure, allocating them all to the same treatment group. Cluster randomisation accounted for the difference in numbers between HBO and NBO groups. As patients presenting simultaneously could be uniquely identified by having identical measurements for three continuous baseline severity measurements (exposure time, time to COHb measurement and time to treatment), any effects due to cluster randomisation could be controlled and adjusted for by including these variables in the generalised linear model. The hyperbaric technicians and nursing staff had knowledge of the treatment group but patients and outcome assessor did not. Interventions Before arrival at Alfred Hospital, non-intubated patients received high flow oxygen by non-occlusive facemask and intubated patients received 100% oxygen. All patients were admitted to hospital, received three treatments on a once-daily basis and continuous oxygen by non-occlusive facemask at 14 L/min (100% oxygen for ventilated patients) between treatments. Patients randomised to NBO therapy were treated for 100 minutes in the multiplace chamber with 100% oxygen at 1.0 atmosphere absolute (ATA). Non-ventilated patients used an occlusive facemask attached via a non-rebreathing valve to a Laerdal adult ventilation bag (1.6 L) with an oxygen reservoir (2.6 L; Armund S Laerdal, Stavanger, Norway). The chamber door was closed and the chamber flushed with air regularly to simulate pressurisation, but the chamber was not pressurised (sham treatment). HBO patients received 100% oxygen by hood, occlusive facemask or mechanical ventilator in the hyperbaric chamber for 100 minutes (60 minutes at 2.8 ATA). After the third treatment, patients were reassessed medically and underwent full neuropsychological assessment. Patients who were clinically abnormal or had poor neuropsychological outcome received three further treatments and received high flow oxygen between treatments. Outcome measures Patient assessment at entry included length of CO exposure, COHb level, time from end of exposure to COHb measurement and to treatment, Mini-mental score and clinical effects of poisoning (Box 2). We then assessed patients at completion of treatment (three or six treatments), and, wherever possible, at one month. We attempted to quantify deficits known to occur in CO poisoning by assessing attention, information processing, memory and learning. A clinical psychologist trained in neuropsychological assessment of brain-injured patients performed all tests at completion of treatment and at follow-up. Computerised testing was used to standardise administration and data-recording procedures and increase objectivity. The tests used were the digit span subtest of the Wechsler Adult Intelligence Scale -- Revised,29 comprising (i) Digit span forward and (ii) Digit span backwards (in which patients are asked to repeat a series of numbers read to them), which measures immediate auditory-verbal memory span, working memory and attention; computerised reaction-time tests,30 consisting of (iii) Simple reaction time (in which subjects are requested to press the space bar on a computer keyboard as soon as they see anything appear on the screen) to give a basal measure of alertness or arousal, and (iv) Choice reaction time (which requires subjects to ignore stimuli in a centre box and to respond selectively to the word "SEVEN" as it appears around the periphery of the computer screen) to test selective attention (reaction time was tested because it can show diffuse cerebral dysfunction, and because processing speed is considered to underlie attention deficits31); (v) a score on the Rey auditory verbal learning test, in which a 15-word list (List A) is presented over five learning trials, followed by an interference trial (List B), after which (vi) Short term free recall is tested without any further presentation of the word list, and (vii) Long term free recall is tested 20 minutes later (this provides a measure of learning across trials, and retention of information following short and long delay periods32). Raw scores of these seven neuropsychological tests were converted to z scores ([score - mean in normal population] / standard deviation), and then t scores (McCall's T; an adjusted z score so that the mean is 50 and the standard deviation is 10).33 Age-based and education-based norms were used where available to calculate t scores. A t score more than one standard deviation below the mean was considered abnormal, and two or more abnormal scores constituted a poor outcome. Patients with poor outcome at hospital discharge were considered to have persistent neurological sequelae (PNS). Delayed neurological sequelae (DNS) were defined as morbidity found at follow-up that was not obvious at hospital discharge, or deterioration of neuropsychological subtest scores by more than one standard deviation. Statistical analyses Statistical analyses were made using mixed linear models to adjust for all baseline covariants (age, sex, suicide attempt, COHb level, time to COHb level, duration of exposure, time to treatment, and presence of other drugs). Data were presented as mean and SD, median and interquartile range (IQR) or number and per cent. Continuous data were first assessed for normality and then analysed by unpaired two-tailed Student's t-test, or Wilcoxon rank sum test. Proportions were compared with chi-squared tests (with Yates' correction), or Fisher's exact test, as appropriate, with multiple logistic regression being used to adjust for confounding factors. We calculated odds ratios and 95% confidence intervals (95% CI) for the difference between proportions. The 95% CI for the difference between means and P values were calculated after adjustment for baseline covariants. All statistical analyses were performed using SAS.34 Results Two hundred and thirty patients with CO poisoning were referred for treatment. Thirty-nine were excluded (one child, eight burns victims, and 30 who refused consent) and treated with HBO. Thus, 191 patients entered the trial (Box 2). Based on the most sensitive neuropsychological test (Short reaction time), with 191 patients and a significance level of 0.05, we had greater than 99% power to detect a 10% difference between groups (ie, 408 seconds v. 450 seconds; SD, 63 seconds) (Clinical Trials Design Program, Biosoft, Cambridge, UK). The groups (104 HBO patients, 87 NBO patients) were comparable in age, sex, incidence of suicide attempt, mechanical ventilation, Mini-mental score, and other markers of severity, including loss of consciousness (coma). Forty-four per cent of patients who had attempted suicide (44% HBO and 44% NBO) also had evidence of self-administration of drugs or alcohol. Most of our patients (73%) had severe CO poisoning, defined by any of the following before or on arrival at Alfred Hospital: a Mini-mental score ≤24, COHb level >30%, confusion, focal neurological deficits, loss of consciousness, electrocardiogram abnormalities, arrhythmias, pulmonary oedema, metabolic acidosis, hypotension, convulsions, and cardiac arrest. All mechanically ventilated patients met the criteria of severe poisoning. Overall mortality was 3%, and the incidence of PNS was 71% at hospital discharge and 62% at follow-up, with no significant differences between the HBO and NBO groups (Box 3). A smaller proportion of NBO patients than HBO patients were considered to be medically or neuropsychologically impaired after three treatments and thus received additional treatments (all patients, 15% v. 28%, P = 0.01; severely poisoned patients, 13% v. 35%, P = 0.001). The only statistically significant difference between groups in neuropsychological performance was in the learning test at completion of treatment (Boxes 3 and 4); this was in favour of the NBO group for both all patients (P = 0.01) and severely poisoned patients (P = 0.005). NBO patients had a significantly lower number of abnormal test results at completion of treatment (all patients, 3.4 v. 2.7, P = 0.02; severely poisoned patients, 3.7 v. 2.6, P = 0.008) and, for those severely poisoned, there were fewer NBO patients with a poor outcome (85% v. 65%; P = 0.03). All five relapses (DNS) occurred in HBO patients (P = 0.03) at a median of 40 days (IQR, 29-81 days) after initial treatment; these patients then received a mean 4.5 (SD, 2.5) additional treatments. Although three of these patients improved with further treatments, all DNS patients had a poor outcome after re-treatment, with a mean 6.3 (SD, 1.2) abnormal test results. The evaluation at completion of treatment showed no difference in outcome between the HBO and NBO groups for patients: treated within four hours of exposure; with severe poisoning and treated within four hours of exposure; who required ventilation; and who were accidentally poisoned (as opposed to those who attempted suicide). Only 46% of patients attended the one-month follow-up. Thus, the numbers in subgroups of interest at one month were small, but showed no difference in any test between HBO and NBO groups. Ten patients had chamber-related complications; seven HBO patients experienced ear barotrauma, one HBO patient developed oxygen toxicity (convulsions) and two patients (one HBO and one NBO) developed severe claustrophobia. The incidence of such complications was thus 9% for HBO and 1% for NBO treatment. Discussion In patients with acute CO poisoning, we found no benefit and possible adverse effects of HBO therapy compared with three days of high-flow NBO. Our multiple comparisons between groups may have produced type 1 errors, and some differences may be spurious. However, differences were consistent and all suggested a more detrimental outcome in the HBO group. Despite multiple comparisons, we found no evidence to support HBO therapy. Our findings thus contrast with those of all other published studies, which have suggested benefit or lack of benefit, but never detriment, from HBO therapy (Box 1). To explain this, careful comparison with previous studies is required. Baseline severity No previous study has compared HBO with NBO in severely poisoned patients. Unlike the non-randomised studies (Box 1) which used HBO for all severely poisoned patients and NBO only for mildly poisoned patients,9,13,16,18-20 all patients in our study were randomised. Of the randomised studies (Box 1), three included patients with mild CO poisoning only12,14,17 (two showing benefit and one no benefit from HBO),17 while the fourth compared one versus two HBO treatments for severely poisoned patients.15Whereas most CO poisoning in the northern hemisphere occurs as a result of heating accidents, in Australia most results from suicide attempts. Not only had a high proportion of our patients (69%) attempted suicide, but, as in other studies,9,35 many (44%) had ingested other drugs. Stratified randomisation equalised this factor between groups and hence could not account for lack of benefit in the HBO group. Further, the six potential factors thought to influence baseline severity (listed in the Methods) were subsequently adjusted for in the generalised linear modelling process. This adjustment also accounted for the small imbalances in the data resulting from cluster randomisation. Carboxyhaemoglobin level Although COHb level is often used as an indicator of the severity of CO poisoning and to determine need for HBO,12-16,20 our findings and other reviews9,14,18,24,36-40 have shown no relationship between COHb level and outcome. COHb level depends on CO exposure, time elapsed to measurement and whether or not oxygen has been given. The low COHb levels in our study (HBO 20.5%; NBO 22%) reflect the delay to the measurement and use of high flow oxygen before measurement. Most previous studies did not report time to measurement and used isolated COHb levels to compare severity of poisoning between groups.12-16,20 Our multivariate analysis showed no correlation between outcome and COHb level even when taking the time to measurement into account. The low COHb levels do not explain the lack of benefit of HBO. Treatment delay Animal studies5 reporting beneficial effects of HBO given immediately after CO exposure cannot readily be extrapolated to clinical practice because treatment delay is to be expected in all clinical scenarios. Our study had a geometric mean treatment delay of 7.1 hours (95% CI, 1.9-26.5 hours), which is longer than in others,14,16,20 but well within entry criteria limits of most studies that report treatment delay15,17,39 (Box 1). Some authors have suggested that the benefits of HBO diminish with treatment delay,12,41 that more than six hours' delay increases DNS and mortality,9 and that treatment delay is associated with increased neuropsychological sequelae.13 Other studies have found treatment delay to be unimportant,42 while some case studies43 and small case series7 report HBO benefit regardless of treatment delays ranging from days to months. Most North American hyperbaric facilities surveyed in 1995 treated CO-poisoned patients who had neurological deficits despite presentation delays ranging from six hours to 56 days,44 and HBO has been advocated for DNS occurring weeks after initial exposure.20,44 In our study, analysis of patients commencing treatment within four hours (all patients or severely poisoned only) showed no differences in outcome between HBO and NBO. We also analysed time to treatment in quartiles (<3, 3-6, 6-12 and >12 hours) and found no difference in outcome between HBO and NBO. Further, multivariate regression analysis did not identify delay in treatment as a predictor of poor outcome. Thus, there was no evidence that delay to treatment might explain the lack of benefit from HBO. Oxygen dose There are no universally accepted recommendations for depth of pressurisation or duration of hyperbaric treatment for CO poisoning (Box 1). The only studies of the benefit of multiple treatments reached contradictory conclusions.13,15,38 Raphael et al15 found no difference in recovery at one month among 286 patients with transient loss of consciousness who received either one or two HBO treatments 12 hours apart. Gorman and Runciman reviewed 13 case series involving 3441 patients and concluded that HBO at 2-3 ATA for 1-2 hours on three or more occasions achieved the lowest mortality, PNS and DNS.38Based on the conclusions of Gorman and Runciman, our study was designed to provide maximum advantage for HBO, with a daily 60-minute treatment at 2.8 ATA on three consecutive days. Because the required dose of NBO for treating CO poisoning is unknown, to ensure we did not undertreat patients, and to maximise similarity of treatment in HBO and NBO groups, all our patients received a treatment on at least three consecutive days and continuous oxygen by non-occlusive facemask at 14 L/min between treatments. Compared with most previous studies, we performed more treatments, of longer duration, at higher ATA and in conjunction with prolonged high flow oxygen therapy between treatments (Box 1). Our HBO group received oxygen therapy equating to approximately 35.7 COHb-dissociation half-lives, while the NBO group received the equivalent of 28.5 COHb-dissociation half-lives. Most other studies have used total oxygen doses of less than 7.0 COHb-dissociation half-lives,9,12,14,15,17 with two series using up to 18 COHb-dissociation half-lives.13,16 It is possible that some of the reported beneficial effects of HBO are purely oxygen-dose related, and that adequate NBO, as given in our study, may achieve the same result. This is supported by an uncontrolled study in which a single HBO treatment had no benefit over NBO, but two or more HBO treatments of 60 minutes at 2.8 ATA resulted in significantly less PNS at hospital discharge and DNS at one month (P < 0.005).13 The apparent worse outcome in our HBO group may also be oxygen-dose related, with higher doses of oxygen adding no further benefit and possibly causing adverse effects. Hampson et al45 (discussing seizures rather than neuropsychological sequelae) have suggested that CO-poisoned patients are at greater risk of brain injury because of the higher ATA used in treatment, concomitant use of other drugs and toxins (particularly in patients who have attempted suicide), as well as the underlying CO poisoning. Assessment of outcome Abnormalities of the basal ganglia, subcortical white matter and hippocampus are the most consistent neuropathological findings in victims of CO poisoning42,46 and are associated with deficits of attention, information processing and memory.47 These deficits can be easily missed on casual assessment or simple neurological examination unless specifically targeted. Studies that did not use neuropsychological assessments9,12,15 reported a lower incidence of PNS than those that did,48 including our study. Appropriately targeted neuropsychological assessment provides the most objective, reliable and sensitive evaluation of outcome after CO poisoning,24,49,50 and in studies that did not report these data9,12,15-17 it is possible that significant adverse effects were missed, making resulting conclusions unreliable. The Carbon monoxide neuropsychological screening battery (CONSB)50 does not adequately measure memory, which may be impaired following CO poisoning.47 The neuropsychological tests we used were therefore more comprehensive than the CONSB, very sensitive to the deficits known to occur in CO poisoning and were computerised (thus increasing objectivity). Further, as one clinical psychologist performed all our testing, interviewer bias was eliminated. Because a full pretreatment neuropsychological assessment was not practical, a Mini-mental examination was used as our baseline neuropsychological assessment, as it gives a global assessment of severity of cerebral injury. Although not ideal, it had the advantages that (i) it could readily be performed by the assessing doctor and quantified, (ii) it enabled us to determine which patients were capable of giving informed consent, and (iii) as it was tested on presentation, completion of treatment and at follow-up, patients served as their own "controls". Our definition of an abnormal test result (>1 SD below the mean) would have included 16% of normal patients. This definition was deliberately chosen to be sensitive to small group differences. We defined a poor outcome as at least two test scores more than one standard deviation below the mean, which would have included less than 2.6% of normal patients. While it is possible that the true incidence of poor outcome or PNS may therefore be slightly lower than we report, the important analyses in making the group comparisons were based on the raw data. Non-randomised studies (Box 1) suggest beneficial effects of HBO, but only two13,20 used neuropsychological tests. One used extensive neuropsychometric evaluation at the one-month review,13 but no evaluation before or at completion of treatment. The other used the CONSB before treatment whenever possible,20 but not after treatment. Of the randomised studies (Box 1), one supplemented clinical assessments with electroencephalogram and cerebral blood flow reactivity to acetazolamide,12 but the clinical relevance of these is uncertain, as the abnormal results were found in patients who were clinically normal. Another used the CONSB, but only after completion of treatment and if patients were "fatigued", the tests were performed in the patients' homes within 12 hours, and a three-month review was only a telephone interview. The lack of baseline assessment, the variable circumstances of immediate outcome assessment and the restricted assessment of delayed outcome greatly limit the interpretation of the findings. Insensitive assessments and lack of blinding may also have missed important differences and created bias in these randomised studies. Study outcomes Our high rate of PNS (compared with previous studies) is probably attributable to our high proportion of severe poisonings (73%) and suicide attempts (69%, likely to be associated with depression and possibly a poor outcome on neuropsychological testing), as well as the comprehensive neuropsychological testing we employed. A type 1 error resulting from multiple testing may have contributed, as well as our cautious definition of PNS (≥2 test scores <1 SD below the mean). The rate of DNS in our study (2.6%) is lower than in most previous reports9,13,16,17,51 (especially given our higher proportion of severe poisonings) and possibly the result of effective treatment with higher doses of oxygen. Our findings differ from those of most published series (Box 1). Although all the non-randomised studies9,11,13,16,18-20 have reported benefit from HBO, none had a control group of matching severity, most had no neuropsychological assessment, and all had low doses of oxygen (brief treatment times) in the NBO groups. With these significant limitations, it is not possible to rely on the conclusions of these studies nor to compare them with adequately conducted randomised trials. None of the four randomised trials included pretreatment or follow-up neuropsychological assessments or sham treatment of the NBO group (our study is unique in doing this). Three did not have blinded outcome assessments. Both randomised trials that concluded there was benefit from HBO12,14 studied only patients with mild CO poisoning, thereby excluding the patients in whom the effects of HBO might be most important. The other two found no benefit in HBO and support our findings.15,17 Mathieu et al found a significantly different incidence of neurological sequelae between HBO and NBO at three-month review (9.5% v. 15%; P = 0.016), but not at completion of treatment, one month, six months or 12 months.17 Raphael et al randomised only mildly poisoned patients,15 and both treatment regimens used (HBO and NBO) have been criticised.38 Interim results (61 patients) of a United States randomised controlled trial enrolling all patients, irrespective of severity of poisoning and also using sham normobaric treatments, found no difference in PNS between NBO and HBO.52 Of the four published randomised studies, the two small ones12,14 reported a benefit from HBO, whereas the two larger studies15,17 did not. If our study is included, three studies involving 1395 patients have now shown no benefit for HBO, compared with two studies involving 91 patients which showed a benefit. Thus, it appears that much of the evidence supporting HBO for CO poisoning is flawed. Although our multiple tests increased the likelihood of a type 1 error, as the main outcome measures (the number of abnormal tests and a "poor outcome") were based on combining all tests we have minimised the chance of a spurious result. Delayed review Despite repeated efforts, only 46% of patients attended for follow-up. This low rate was probably affected by many of our patients having characteristics associated with suicide attempts and depression, many being referred from distant locations, and lack of incentive. However, the follow-up rate was equal in both groups, and evenly distributed across subgroups. Our follow-up assessment was more comprehensive than in all but one other study,13 but failed to show benefit for HBO. Others studies have had significant non-attendance rates at delayed review of 11%-47%.12-15,19,48 Most studies do not quote the "drop-out" rate.9,16-18,20 Conclusion Our prospective, randomised controlled trial of CO-poisoned patients of all severities attempted to address the shortcomings of previous studies by incorporating sham treatments for the NBO group, blinded outcome assessment and extensive neuropsychological assessment. Our HBO protocol was designed to provide the maximum potential advantage for HBO therapy based on currently available knowledge. When compared with three days of normobaric oxygen, we could find no evidence that treatment with HBO was beneficial to outcome and therefore do not recommend its use. References Meredith T, Vale A. Carbon monoxide poisoning. BMJ 1988; 2 96(6615): 77-79. Tibbles PM, Perrotta PL. Treatment of carbon monoxide poisoning: a critical review of human outcome studies comparing normobaric oxygen with hyperbaric oxygen. Ann Emerg Med 1994; 24: 269-276. Pace N, Strajman E, Walker EL. Acceleration of carbon monoxide elimination in man by high pressure oxygen. Science 1950; 111: 652-654. Tibbles PM, Edelsberg JS. Hyperbaric-oxygen therapy. N Engl J Med 1996; 334: 1642-1648. Brown SD, Piantadossi CA. In vivo binding of carbon monoxide to cytochrome c oxidase in rat brain. J App Physiol 1990; 68: 604-610. Dean BS, Verdile VP, Krenzelok EP. Coma reversal with cerebral dysfunction recovery after repetitive hyperbaric oxygen therapy for severe carbon monoxide poisoning. Am J Emerg Med 1993; 11: 616-618. Myers RAM, Snyder SK, Linberg S, Adams Cowley R. Value of hyperbaric oxygen in suspected carbon monoxide poisoning. JAMA 1981; 246: 2478-2480. Thomson LF, Mardel SN, Jack A, Shields TG. Management of the moribund carbon monoxide victim. Arch Emerg Med 1992; 9: 208-213. Goulon M, Barois A, Rapin M, et al. Carbon monoxide poisoning and acute anoxia due to breathing coal gas and hydrocarbons. J Hyperbar Med 1986; 1: 23-41. Yang ZD, Sun CQ, Cao XL. Clinical analysis of the effect with hyperbaric oxygen therapy on 672 cases with acute carbon monoxide poisoning. J Hyperbar Med 1986; 1: 188. Roche L, Bertoye A, Vincent P. Comparison de deux groupes de vingt intoxications oxycarbonees traitees par oxygenenormobare et hyperbare. Lyon Med 1968; 49: 1483-1499. Ducasse JL, Celsis P, Marc-Vergnes JP. Non-comatose patients with acute carbon monoxide poisoning: hyperbaric or normobaric oxygenation? Undersea Hyperb Med 1995; 22: 9-15. Gorman DF, Clayton D, Gilligan JE, Webb RK. A longitudinal study of 100 consecutive admissions for carbon monoxide poisoning to The Royal Adelaide Hospital. Anaes Intens Care 1992; 20: 311-316. Thom SR, Taber RL, Mendiguren II, et al. Delayed neuropsychologic sequelae after carbon monoxide poisoning: prevention by treatment with hyperbaric oxygen. Ann Emerg Med 1995; 25: 474-480. Raphael J, Elkharrat D, Jars-Guincestre M, et al. Trial of normobaric and hyperbaric oxygen for acute carbon monoxide intoxication. Lancet 1989; 2: 414-419. Mathieu D, Nolf M, Durocher A, et al. Acute carbon monoxide poisoning: risk of late sequelae and treatment by hyperbaric oxygen. J Toxicol Clin Toxicol 1985; 23: 315-324. Mathieu D, Wattel F, Mathieu-Nolf M, et al. Randomized prospective study comparing the effect of HBO versus 12 hours NBO in non-comatose CO poisoned patients: results of the interim analysis. Undersea Hyperb Med 1996; 23 Suppl: 7. Willms SJ, Turner F, Kerr J. Carbon monoxide or smoke inhalations treated with oxygen (hyperbaric vs normobaric): 118 reviewed. Undersea Biomed Res 1985; 12 Suppl: S56. Ely EW, Moorehead B, Haponik EF. Warehouse workers' headache: emergency evaluation and management of 30 patients with carbon monoxide poisoning. Am J Med 1995; 98: 145-155. Myers RAM, Snyder SK, Emhoff TA. Subacute sequelae of carbon monoxide poisoning. Ann Emerg Med 1985; 14: 1163-1167. Weaver LK, Hopkins RO, Larson-Lohr V. Hyperbaric oxygen and carbon monoxide poisoning. Ann Emerg Med 1995; 26: 390-391. Mitchell CA, Carroll PA. Acute toxicity of inhaled gases and particulates. Med J Aust 1989; 150: 717-720. Seger D. The science (or lack thereof) in the treatment of carbon monoxide poisoning. Am J Emerg Med 1994; 12: 389. Seger D, Welch L. Carbon monoxide controversies: neuropsychological testing, mechanism of toxicity, and hyperbaric oxygen. Ann Emerg Med 1994; 24: 242-248. Olson KR, Seger D. Hyperbaric oxygen for carbon monoxide poisoning: does it really work? Ann Emerg Med 1995; 25: 535-537. Van Meter KW, Weiss L, Harch PG, et al. Should the pressure be off or on in the use of oxygen in the treatment of carbon monoxide-poisoned patients. Ann Emerg Med 1994; 24: 283-288. Weaver LK. Randomized clinical trial in carbon monoxide poisoning needed. Am J Emerg Med 1994; 12: 685. Folstein MF, Folstein SE, McHugh PR. Minimental state. J Psychiatr Res 1975; 12: 189-198. Wechsler D. Wais-R manual. New York: Psychological Corporation, 1981. Miller EN, Satz P. The Californian computerised assessment package (Calcap). Los Angeles, CA: Miller EN & Satz P, 1987. Van Zomeren AH, Brouwer WB. Clinical neuropsychology of attention. New York: Oxford University Press, 1994. Lezak MD. Neuropsychological assessment. New York: Oxford University Press, 1995. Howell DC. Statistical methods for psychology. 2nd ed. Boston: Duxbury Press, 1987. Littell RC, Milliken GA, Stroup WW, Wolfinger RD. SAS [computer program]. Version 6.12. Cary, NC: SAS Institute Inc, 1996. Power BM, Prentice DA. Carbon monoxide poisonings at The Royal Perth Hospital. Anaesth Intens Care 1991. 19: 149. Myers RAM. Planning an effective strategy for carbon monoxide poisoning. Emerg Med Rep 1987; 8: 193-201. Runciman WW, Gorman DF. Carbon monoxide poisoning: from old dogma to new uncertainties. Med J Aust 1993; 158: 439-440. Gorman DF, Runciman WB. Carbon monoxide poisoning. Anaesth Intens Care 1991; 19: 506-511. Norkool DM, Kirkpatrick JN. Treatment of acute carbon monoxide poisoning with hyperbaric oxygen: a review of 115 cases. Ann Emerg Med 1985; 14: 1168-1171. Choi IS. Delayed neurologic sequelae in carbon monoxide intoxication. Arch Neurol 1983; 40: 433-435. Origani G, Michael M, Tuscano R, Arghetti S. Outcome of patients suffering from CO poisoning. Undersea Hyperb Med 1996. 23 Suppl: 83. Pracyk JB, Stolp BW, Fife CE, et al. Brain computerized tomography after hyperbaric oxygen therapy for carbon monoxide poisoning. Undersea Hyperb Med 1996; 22: 1-7. Samuels AH, Vamos MJ, Taikato MR. Carbon monoxide, amnesia and hyperbaric oxygen therapy. Aust N Z J Psychiatry 1992; 26: 316-319. Hampson NB, Dunford RG, Kramer CC, Norkool DM. Selection criteria utilized for hyperbaric oxygen treatment of carbon monoxide poisoning. J Emerg Med 1995. 13: 227-231. Hampson NB, Simonson SG, Kramer CC, Piantadosi CA. Central nervous system oxygen toxicity during hyperbaric treatment of patients with carbon monoxide poisoning. Undersea Hyperb Med 1996; 23: 215-219. Miura T, Mitoma M, Kawai R, Harada K. CT of the brain in acute carbon monoxide intoxication: characteristic features and prognosis. Am J Neuroradiol 1985; 6: 739-742. La Plane D, Baulac M, Widlocher D, Dubois B. Pure psychic akinesia with bilateral lesions of basal ganglia. J Neurol Neurosurg Psychiatry 1984; 47: 377-385. Hopkins RO, Weaver LK. Long-term outcome in subjects with carbon monoxide poisoning. Undersea Hyperb Med 1994; 21 Suppl: 17. Starkstein SE, Berthier ML, Leigurada R. Psychic akinesia following bilateral pallidal lesions. Int J Psychiatry Med 1989; 19: 155-164. Messier LD, Myers RAM. A neuropsychological screening battery for emergency assessment of carbon monoxide-poisoned patients. J Clin Psychol 1991; 47: 675-684. Hopkins RO, Weaver LK. Does late repetitive hyperbaric oxygen improve delayed neurologic sequelae associated with carbon monoxide poisoning? Undersea Biomed Res 1991; 18 Suppl: 34. Weaver LK, Hopkins RO, Larson-Lohr V, et al. Double-blind, controlled, prospective, randomized clinical trial (rct) in patients with acute carbon monoxide (CO) poisoning: outcome of patients treated with normobaric oxygen or hyperbaric oxygen -- an interim report. Undersea Hyperb Med 1995; 22 Suppl: 14. (Received 25 Mar, accepted 1 Dec, 1998) Authors' details Alfred Hospital, Melbourne, VIC. Carlos D Scheinkestel, FRACP, DipDHM, Deputy Director, Department of Intensive Care and Hyperbaric Medicine, and Head, General Intensive Care Unit; Paul S Myles, MD, FANZCA, Head of Research, Department of Anaesthesia and Pain Management; D James Cooper, MD, FRACP, Head, Trauma Intensive Care Unit; Ian L Millar, FAFOM, DipDHM, Head, Hyperbaric Medicine; David V Tuxen, MD, FRACP, Director, Department of Intensive Care and Hyperbaric Medicine. Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, VIC. Michael Bailey, BSc, MSc(Stat), Statistical Consultant. School of Psychological Science, La Trobe University, Melbourne, VIC. Kerry Jones, BBSc(Hons), MPsych, Psychologist, and PhD student. Reprints: Dr C D Scheinkestel, Department of Intensive Care and Hyperbaric Medicine, Alfred Hospital, Commercial Road, Prahran, Melbourne, VIC 3181. Email: cdschATozemail.com.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> 1: Published trials of carbon monoxide poisoning treated with hyperbaric oxygen (HBO) and normobaric oxygen (NBO)StudyPatients includedNo. HBO patientsNo. NBO patientsBlindedNeuropsychological testsNon-randomised Roche et al11All2020NoNo Mathieu et al16All20327NoNo Myers et al20All13182NoYes Willms et al18All7246NoNo Goulon et al9All27329NoNo Gorman et al13All928NoYes Ely et al19All426NoNoRandomised Raphael et al15Non-comatose Severely poisoned173 145170 141No NoNo No Thom et al14Mildly poisoned3332NoYes Ducasse et al12Non-comatose1313YesNo Mathieu et al17Non-comatose299276NoNo This study*All10487YesYesStudyNumber of treatmentsMaximum ATATime at maximum ATA (min)Entry criteria time to treatment (h)Actual time to treatment (h)HBO benefit reportedNon-randomised Roche et al111-102.560??Yes Mathieu et al161-52.590?~4Yes Myers et al20?1.8-2.046?1-1.5Yes Willms et al1832.5???Yes Goulon et al92290??Yes Gorman et al131, 2, >22.860??Yes Ely et al1912.5120??YesRandomised Raphael et al151 1 v. 22 2120 12012 12? ?No No Thom et al141 2.8 230 90 <6 ~1 Ducasse et al121???~1Yes Mathieu et al1712.59012?No This study*≥32.860<247.1 (95% CI, 1.9-26.5)NoATA = atmospheres absolute; HBO = hyperbaric oxygen; NBO = normobaric oxygen; ? = not reported; ~ = approximately. * Our study was the only one listed in which there were sham treatments for NBO patients. 2: Patient characteristics and description of severity of carbon monoxide poisoning for patients treated with hyperbaric oxygen (HBO) and normobaric oxygen (NBO)HBO (n = 104)NBO (n = 87)PDemographic characteristics Age37.8 (35.1-40.5)34.8 (32.0-37.6)0.13+ Male89 (86%)67 (77%)0.13++ Suicide attempt68 (65%)63 (72%)0.3++Baseline severity Ventilated20 (19%)16 (18%)0.88++ Exposure time (h)2.6 (2.0-3.2)2.5 (1.9-3.1)0.87+ Time to carboxyhaemoglobin level (h)*3.2 (2.6-3.8)2.6 (2.1-3.1)0.11+ Carboxyhaemoglobin level (%)20.5 (18.0-23.0)22.0 (19.6-24.4)0.39+ Time to treatment (h)*7.5 (6.6-8.6)6.6 (5.7-7.5)0.16+ Mini-mental score27.0 (26.1-27.9)26.4 (25.4-27.4)0.27+ No. with criteria for severe poisoning72 (69%)67 (77%)0.23++Signs Coma53 (51%)49 (56%) Acidosis11 (11%)13 (15%) Focal neurological deficits9 (9%)6 (7%) Electroencephalogram changes7 (7%)9 (10%) Hypotension3 (3%)2 (2%) Arrhythmias2 (2%)7 (8%) Pulmonary oedema2 (2%)1 (1%) Convulsions1 (1%)3 (3%) Cardiac arrest1 (1%)1 (1%)Symptoms Headache55 (53%)38 (44%) Fatigue47 (45%)38 (44%) Difficulty in thinking46 (44%)37 (43%) Dizziness38 (37%)21 (24%) Nausea38 (37%)25 (29%) Acute confusional state20 (19%)10 (11%) Paraesthesiae11 (11%)6 (7%) Visual disturbance9 (9%)4 (5%) Palpitations8 (8%)3 (3%) Chest pain7 (7%)3 (3%) Tinnitus4 (4%)2 (2%) Abdominal pain3 (3%)0 Diarrhoea2 (2%)2 (2%)Figures are number (%) or mean (95% CI). HBO = hyperbaric oxygen; NOB = normobaric oxygen. *Geometric mean; +t test; ++chi-squared test. 3: Neuropsychological outcome for all patients treated with hyperbaric oxygen (HBO) and normobaric oxygen (NBO)HBO (n = 104)NBO (n = 87)Difference (95% CI) in favour of HBO*PAt end of treatment No. requiring >3 treatments29 (28%)13 (15%)OR 2.8 (1.3-6.2)++0.01++ Deaths3 (3%)3 (3.4%)0.96++Average neuropsychological test results+ Simple reaction time (s)385375-10 (-50 to 30)0.63s Choice reaction time (s)10.411.1-0.7 (-1.9 to 0.5)0.25s Digit span forward (no. digits recalled)8.28.10.1 (-9 to 1.1)0.87s Digit span backwards (no. digits recalled)5.35.6-0.3 (-1.1 to 0.5)0.55s Rey auditory verbal learning test (score)42.247.7-5.5 (-9.8 to -1.2)0.01s Short term free recall (no. objects)3.23-0.2 (-1.1 to 0.7)0.54s Long term free recall (no. objects)4.44.2-0.2 (-1.5 to 1.1)0.76s Improvement in Mini-mental score00.7-0.7 (-2.7 to 1.3)0.53sAverage number of abnormal tests 3.42.7-0.7 (-1.3 to -0.1)0.02sPoor outcome (PNS)0.740.68OR 1.7 (0.8-4.0)++0.19++Relapse (DNS)5 (4.8%)00.03**Figures are number (%) or mean (95% CI). HBO = hyperbaric oxygen; NBO = normobaric oxygen; OR = odds ratio; PNS = persistent neurological sequelae (>2 abnormal test results); DNS = delayed neurological sequelae. *After adjustment for age, sex, suicide attempt, carboxyhaemoglobin (COHb) level, time to measurement of COHb level, duration of exposure, time to treatment, presence of other drugs; +See Methods section for description of neuropsychological tests; ++chi-squared test; sF-test; **Fisher's exact test. 4: Characteristics of 139 patients with severe carbon monoxide poisoning, and the neurophysiological outcome for this subgroupHBO (n = 72)NBO (n = 67)Difference (95% CI) in favour of HBO*P*Demographic characteristics Age38.6 (35.2-42.0)36.7 (33.5-39.9)0.42** Male60 (83%)55 (82%)0.99s Suicide55 (76%)54 (81%)0.69++Baseline severity Ventilated20 (28%)16 (24%)0.74s Exposure time (h)2.5 (1.9-3.1)2.2 (1.6-2.8)0.45** Time to carboxyhaemoglobin level (h)+2.9 (2.3-3.7)2.2 (1.9-2.7)0.07** Carboxyhaemoglobin level (%)+23.0 (19.8-26.2)22.9 (22.0-25.8)0.94** Time to treatment (hours)7.3 (6.3-8.5)6.1 (5.4-6.9)0.08** Mini-mental score25.6 (24.3-26.9)25.8 (24.5-27.1)0.8**At end of treatment No. requiring >3 treatments25 (35%)9 (13%)OR 5.4 (2.0-14.8)0.001s Deaths3 (4.2%)3 (4.5%)OR 1.0 (0.2-6.0)0.97sAverage neuropsychological test results+ Simple reaction time (s)410377-33 (-72 to 6.0)0.01ss Choice reaction time (s)9.910.7-0.8 (-2.4 to 0.8)0.32ss Digit span forward (no. digits recalled)7.98-0.1 (-1.3 to 1.1)0.91ss Digit span backwards (no. digits recalled)55.5-0.5 (-1.6 to 0.6)0.35ss Rey auditory verbal learning test (score)4249.2-7.2 (-12.2 to -2.2)0.005ss Short term free recall (no. objects)43.5-0.5 (-1.7 to 0.7)0.43ss Long term free recall (no. objects)4.65.20.6 (-1.1 to 2.3)0.47ss Improvement in Mini-mental score21.60.4 (-0.2 to 2.8)0.71ssAverage number of abnormal tests3.72.6-1.1 (-1.9 to -0.3)0.008ssPoor outcome (PNS)0.850.65OR 3.6 (1.1-11.9)0.03sFigures are number (%) or mean (95% CI). HBO = hyperbaric oxygen; NBO = normobaric oxygen; OR = odds ratio; PNS = persistent neurological sequelae (>2 abnormal test results); DNS = delayed neurological sequelae. *After adjustment for age, sex, suicide attempt, carboxyhaemoglobin (COHb) level, time to measurement of COHb level, duration of exposure, time to treatment, presence of other drugs; +Geometric mean (95% CI); ++See Methods section for description of neuropsychological tests; schi-squared test; **t-test; ssF-test.

Carlos D Scheinkestel · Michael Bailey · Paul S Myles · Kerry Jones · Ian L Millar · David V Tuxen

Medical Detective Lead poisoning from drinking Kombucha tea brewed in a ceramic pot Tri Giang Phan, Jane Estell, Geoffrey Duggin, Ian Beer, Diane Smith and Mark J Ferson MJA 1998; 169: 644-646 Kombucha tea is an alternative therapy that is gaining popularity as a remedy for a diverse range of ailments. We report two cases of symptomatic lead poisoning requiring chelation therapy in a married couple who had been drinking Kombucha tea for six months, brewing the tea in a ceramic pot. We postulate that acids in the tea eluted lead from the glaze pigment used in the ceramic pot, in a manner analogous to elution of lead from crystal decanters by wine and spirits. Introduction - Clinical record - Discussion - References - Authors' details - - More articles on Toxicology Introduction Lead is a ubiquitous enzymatic poison which can be found in the air, soil and drinking water. The addition of lead salts to paint at the beginning of the 19th century, and tetraethyl lead to petroleum in the 20th century, has increased environmental levels of lead, particularly in dense urban areas.1 Less-common sources of lead include cosmetics, ceramics, leaded crystal and old newsprint. Daily ingestion of more than 5 µg of lead/kg body weight will result in a positive lead balance and rising lead levels.2 Lead preferentially binds to the sulfhydryl groups of proteins and denatures them, causing cell death and tissue inflammation. Impaired haemopoiesis results in sideroblastic anaemia. Damage to the kidney may result in tubular necrosis and renal failure, Fanconi syndrome (type 2 proximal renal tubular acidosis), saturnine gout, and hypertension. Neurotoxicity may result in peripheral neuropathy, sensorineural deafness, metabolic encephalopathy, and neurodevelopmental delay. Colicky abdominal pain and constipation are frequent presenting symptoms. We report two cases of lead poisoning in a married couple who had been drinking Kombucha tea brewed in a ceramic pot. The tea is a mildly alcoholic beverage produced by fermenting sweet black tea with the Kombucha "mushroom" in a glass, porcelain or ceramic pot. The mushroom itself is a symbiosis of yeast and bacteria bound by a thin, permeable membrane. It is gaining popularity as an alternative therapy for a diverse range of ailments such as insomnia, hair loss, impotence, obesity, chronic fatigue syndrome, asthma, multiple sclerosis, rheumatoid arthritis, cancer, and AIDS.3 Clinical record A 58-year-old woman presented to the Emergency Department at the Prince of Wales Hospital with a six-week history of increasing constipation and colicky abdominal pain. She was treated with laxatives and discharged. Review of her blood film showed a hypochromic anaemia (Hb, 108 g/L) with polychromasia and basophilic stippling of her red blood cells (Figure 1). Lead poisoning was suspected, and a urine lead level was ordered. Iron studies and a haemoglobin electrophoretogram were normal. Her 24-hour urinary lead level was 1.42 µmol/L (normal range, 0.0-0.4 µmol/L) and her blood lead level was 5.95 µmol/L (normal range, 0.0-0.48 µmol/L). Her 63-year-old husband was found to have a blood lead level of 4.49 µmol/L. He was a retired telephone operator who had had no exposure to lead during his working life. His only symptom was fatigue. They had no children and there were no family pets. Six months earlier both the patient and her husband started drinking Kombucha tea as a tonic. They brewed the tea in a ceramic pot and ingested one tall glass (about 250 mL) every morning. An elevated blood lead level has been notifiable under the Public Health Act 1991 (NSW) since 1 December 1996; accordingly, the South Eastern Sydney Public Health Unit was notified. Samples of soil, paint chips, household dust, and dust from venetian blinds were taken from the family home and analysed. No environmental source of lead was found. However, samples of the Kombucha tea contained 173 mg/kg of lead. The Australian Food Standards Code A12 -- Metals and Contaminates in Food requires a lead level of less than 0.2 mg/kg in beverages and other liquid foods. After brewing in the ceramic pot, the Kombucha mushroom contained 329 mg of lead/kg dry weight, the maximum permitted being 0.5 mg/kg. The tea was brewed in a ceramic pot with internal glazing (Figure 2), and testing found a lead level of 198 mg/L of extract solution. The Food (General) Regulation 1997 (NSW) requires food vessels to comply with the British Standard Specification of Limits of Metal Release from Ceramic Ware, Glassware, Glass Ceramic Ware and Vitreous Enamel Ware (BS 6748: 1986), which specifies a maximum lead level of 4.0 mg/L of extract solution. This standard refers to containers used for food storage, and it is likely that the ceramic pot, which had been imported from Spain 25 years earlier, was not intended for food use. Both patients were offered outpatient chelation therapy with calcium disodium edetate. They received a course of five intravenous infusions of one gram of calcium disodium edetate given at two-day intervals. At follow-up six months later, the woman's anaemia and constipation had resolved and her blood lead level had fallen to 1.42 µmol/L. Her husband remained symptom-free and his blood lead level had fallen to 1.52 µmol/L. Discussion Lead contamination of food and beverages has long been recognised. In 1991, Graziano and Blum showed that wine and spirits stored in crystal decanters could elute lead from the vessel over time to produce potentially highly toxic levels of lead.4 They correlated the rise in the lead concentration in port or brandy with the lead content of the crystal decanter and the time that the port or brandy was decanted. In fact, lead poisoning has been postulated as the cause of the epidemics of gout in the nobles of 18th- and 19th-century Britain and the aristocrats of the Roman Empire.5 The consumption of port in England in the 18th and 19th century was paralleled by the high incidence of gout, and lead levels in fortified wines bottled between 1770 and 1820 are as high as 300-1900 µg/L.5 The pandemics of gout among Roman aristocrats have also been linked to chronic lead poisoning from contaminated wines. Roman wines contained boiled-down grape syrup (sapa), which had to be simmered in either a lead pot or a lead-lined copper kettle. Attempts to prepare sapa according to ancient recipes have produced lead concentrations of 240-1000 mg/L of boiled-down must.6 Nriagu reviewed the lifestyles of the Roman emperors and usurpers, and speculated that their predilection for lead-tainted Apician entrees7 and Columellan wine blends8 contributed to widespread plumbism and the fall of the Roman Empire.9In a report similar to ours, Scarlett et al described lead poisoning in a married couple who ingested non-alcoholic carbonated beverages from a pewter drinking mug.10 Traditional pewter mugs contain 25% lead and 75% tin, and are not recommended for food and drink containers. Highly toxic lead concentrations may result from elution of lead from the pewter by the acidity of effervescent non-alcoholic beverages. Kombucha tea contains 0.5%-1.5% alcohol, and organic acids such as acetic and lactic acid, which produce a pH of 2.5.11 The literature on Kombucha recommends the tea be brewed in a glass, porcelain or ceramic pot to obtain the best results.3 However, some decorative bowls contain high levels of lead oxide in the glaze or pigments used in the ceramics. Acidic beverages stored in these containers may elute the heavy metal from the bowl and produce harmful levels of lead in the brew, in a manner analogous to the elution of lead from crystal decanters by wine and spirits, and from pewter by non-alcoholic carbonated beverages. Failure to fire the kiln to a high enough temperature during glazing can result in inadequate fixation of the glaze pigments to the ceramic bowl, which can potentiate this effect. Kombucha tea itself has been associated with toxic reactions. There have been two case reports from Iowa of unexplained severe illness associated with drinking Kombucha tea.12 Both patients had a severe metabolic acidosis with high serum levels of lactate, the cause of which could not be determined. There have also been warnings of potential hepatotoxicity following the report of a man who developed a skin rash, hepatomegaly and abnormal liver function tests after drinking the tea for one month.11 His symptoms resolved and his liver function tests normalised when he stopped taking the tea. In another four cases, one patient developed jaundice and abnormal liver function tests, the second had non-specific complaints of dry mouth, dizziness, nausea and vomiting, and neck pain, and the other two patients were thought to have developed allergic reactions.13 The history of chronic ingestion of Kombucha tea over six months and demonstration of highly toxic levels of lead in both the tea and mushroom confirm that it was the source of the lead poisoning in our patients. We postulate that their exposure to lead (estimated to be about 43 mg/day) resulted from ingestion of Kombucha tea which had been brewed in a ceramic pot that was not properly glazed and was probably never intended for food storage. This method of brewing is potentially harmful. Patients with unexplained lead poisoning should be questioned about their use of alternative therapies, and their methods of food preparation and storage. References Graef J. Lead poisoning. Part I. Clinical Toxicology Review 1992; 14(8). Graef J. Lead poisoning. Part II. Clinical Toxicology Review 1992; 14(9). Tietze HW. Kombucha the miracle fungus. 6th ed. Bermagui, NSW: Harald Tietze Publications, 1995. Graziano JH, Blum C. Lead exposure from lead crystal. Lancet 1991; 337: 141-142. Ball GV. Two epidemics of gout. Bull Hist Med 1971; 45: 401-408. Gilfillan SC. Lead poisoning and the fall of Rome. J Occup Med 1965; 7: 53-60. Apicius. The art of cooking. Flower B, Rosenbaum E, translators. London: George G Harrap, 1958. Columella. De re rustica 12: 20. Nriagu JO. Saturnine gout among Roman aristocrats. Did lead poisoning contribute to the Fall of the Empire? N Engl J Med 1983; 308: 660-663. Scarlett JD, Hodges RJ, Romain PR, et al. Lead poisoning by a mug. Med J Aust 1995; 163: 589-590. Perron AD, Patterson JA, Yanofsky NN. Kombucha "mushroom" hepatotoxicity [letter]. Ann Emerg Med 1995: 26; 660-661. Unexplained severe illness possibly associated with consumption of Kombucha tea -- Iowa 1995. MMWR Morb Mortal Wkly Rep 1995; 44: 892-893, 899-900. Srinivasan R, Smolinske S, Greenbaum D. Probable gastrointestinal toxicity of Kombucha tea. Is this beverage healthy or harmful? J Gen Intern Med 1997; 12: 643-644. Authors' details Royal Prince Alfred Hospital, Camperdown, NSW. Tri Giang Phan, MB BS, Renal Registrar; Geoffrey Duggin, MB BS, FRACP, Head, Toxicology Unit. Prince of Wales Hospital, Randwick, NSW. Jane Estell, BMed, Haematology Registrar. South Eastern Sydney Public Health Unit, Zetland, NSW. Ian Beer, Diploma of Public Health Inspection, Food Inspector; Diane Smith, Environmental Health Officer; Mark J Ferson, FRACP, FAFPHM, Director. Reprints will not be available from the authors. Correspondence: Professor G Duggin, Department of Renal Medicine, Royal Prince Alfred Hospital, Missenden Road, Camperdown, NSW 2050. Email: gdugginATrenicu.rpa.cs.nsw.gov.au Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Jane Estell · Geoffrey Duggin · Ian Beer · Diane Smith · Mark J Ferson

The impact of catalytic converters on motor vehicle exhaust gas suicides Virginia H Routley and Joan Ozanne-Smith MJA 1998; 168: 65-67 Abstract - Introduction - Methods - Results - Discussion - Acknowledgments - References - Authors' details - - ©MJA1998 Abstract Objective: To examine the trends in motor vehicle exhaust gas suicides since 1970 and to investigate the impact of catalytic converters. Design: Australia-wide database analyses and a retrospective stratified series of 100 Victorian cases. Data sources: Australian Bureau of Statistics, 1970-1995; Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1991/92-1995/96; Victorian Coroner's files, 1994-1996. Results: There were 509 motor vehicle exhaust gas suicides in Australia in 1995, representing 22% of total suicides. Since the 1986 requirements for reduced carbon monoxide emissions from new vehicles (and thus the use of catalytic converters), the absolute numbers and rates of such suicides have increased, and they have come to represent a larger percentage of total suicides. Of 75 Victorian victims' vehicles traced, 36% were manufactured during or after 1986, showing that exhaust gas suicides have occurred in vehicles with catalytic converters. Blood carboxyhaemoglobin levels did not differ between victims using vehicles with or without catalytic converters. Between 1976 and 1991 exhaust gas suicides increased at a faster rate than motor vehicle registrations. Australian hospital admissions for exhaust gas suicide attempts have increased substantially since 1991-1992. Conclusion: Catalytic converters and the associated lower CO emission limits of 9.3 g/km had not, by 1995, resulted in a reduction in numbers, rates or percentages of exhaust gas suicides in Australia. Introduction Suicide is a major problem in Australia, with approximately 2000 deaths from suicide annually in recent years. Since 1990 suicide has become a more common cause of death than motor vehicle crashes. In 1995, suicide by motor vehicle exhaust gas accounted for 509 deaths and was second only to hanging. It was most commonly used by males (85%), especially those aged 20-50 years. Rates of motor vehicle exhaust gas suicide per 100 000 population in Australia were 4.69 for males, 1.02 for females and 2.85 total (Australian Institute for Suicide Research and Prevention, 1996; unpublished data). Further, motor vehicle exhaust gas related self-harm represented a smaller proportion of patients hospitalised for attempted suicide than of successful suicides (2.0% v. 21.6%; Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1996; unpublished data), indicating the high lethality of this means of suicide. Motor vehicle availability has been found to be related to exhaust gas suicides,1 and in Australia the rates of such suicides in different States vary to some extent with motor vehicle registration rates. For example, the Northern Territory has the lowest rates for each, while Western Australia has relatively high rates (Australian Institute of Health and Welfare, National Injury Surveillance Unit, 1996; unpublished data).2 Carbon monoxide (CO), the most toxic component of motor vehicle exhaust gas, is colourless, odourless and tasteless and is produced from the incomplete combustion of organic fuels. Mild CO poisoning produces headache and drowsiness; more severe poisoning leads to collapse, coma and death.3 Other effects can include myocardial infarction, deterioration of personality and impaired memory.4,5 Environmental regulations have required carbon monoxide emission levels from vehicle exhausts to be reduced over past decades. The required maximum levels have been 24.3 g/km from July 1976 (Australian Design Rule [ADR] 27A), 9.3 g/km from 1986 for new passenger vehicles (ADR 37-00) and 2.1 g/km for new models (ADR 37-01) from 1997 and for all new passenger vehicles from 1998. To cope with the unleaded petrol legally required since 1986 to reduce environmental air pollution from exhaust emissions, vehicles usually require catalytic converters (ADR 37-00; Australian Standard 2877). These convert carbon monoxide and other pollutants into the by- products, carbon dioxide and water. The purposes of this study were to examine overall trends in exhaust gas suicides, and to investigate the impact of the 1986 reduction in allowable carbon monoxide emissions (or the effects of catalytic converters) on that suicide rate. Methods To examine the trends in exhaust gas suicide between 1970 and 1995, we analysed Australia-wide data for mortality from motor vehicle exhaust gas suicides and for total suicides by age, sex and State of residence obtained from the Australian Bureau of Statistics (ABS). We examined Australian hospital admissions data from the Australian Institute of Health and Welfare, National Injury Surveillance Unit for admissions related to motor vehicle exhaust gas suicide attempts. Rates for suicide by motor vehicle exhaust gas were obtained from the Australian Institute for Suicide Research and Prevention. Data on vehicle numbers, rates per head of population and year of manufacture were obtained from ABS publications. Australian exhaust gas suicides and motor vehicle registration rates were compared for the ABS Motor Vehicle Census years since 1970. To examine the effects of catalytic converters, we undertook a retrospective stratified case series study of 100 exhaust gas suicides in Victoria between 1 January 1994 and 31 December 1996, noting the year of manufacture of the motor vehicles involved and victims' blood levels of carboxyhaemoglobin (COHb) -- a reflection of carbon monoxide levels. We compared COHb levels in victims whose suicides involved vehicles manufactured before 1986 with those whose vehicles were manufactured from 1986 (when CO emission levels were reduced). Cases of exhaust gas suicide in 1994 were obtained from a Victorian State Coroner's Office publication,6 while those in 1995 and 1996 were obtained from the Victorian Coroner's Facilitation System database. Results Since 1975 there have been approximately 7000 motor vehicle exhaust gas suicides in Australia. Suicides show an increasing trend, with dips in 1979 and 1993 (R2 = 0.58), while motor vehicle registrations follow an exponential trend (R2 = 0.88), showing a steady rise (Figure 1). Between 1979 and 1991 such suicides increased at a faster rate than motor vehicle registrations. Motor vehicle exhaust gas suicides have steadily increased as a percentage of total suicides since at least 1970 (7% in 1970, 13% in 1980 and 22% in 1995). Hospital admissions for Australian motor vehicle exhaust gas suicide attempts have increased steadily in recent years (1994/95 data are not available), with the data showing an exponential trend (R2 = 0.99). Deaths also increased, but show no clear trend (Figure 2). The 100 cases of exhaust gas suicide obtained from the records of the Victorian Coroner comprised 33 of a total of 96 in 1994, 33 of 140 in 1995, and 34 of 136 in 1996. The year of vehicle manufacture had been recorded for only 75 of these cases (25 in each of 1994, 1995 and 1996). Of these 75, 20% in 1994, 56% in 1995 and 32% in 1996 involved vehicles manufactured in 1986 or later. In total, 27 of the 75 vehicles (36%) were 1986 models or later. This proportion is not significantly different (P = 0.62) from the 39% of vehicles manufactured in 1986 or later in the total Victorian fleet of 2 799 310 vehicles in May 1995 (ABS 1995 Motor Vehicle Census).2 For the 74 cases in which both the victim's COHb level and the age of the vehicle was known, 26 involved vehicles manufactured in 1986 or later and 48 involved earlier models. The median COHb level of victims in these two groups was identical (77.1%). Discussion Motor vehicle exhaust gas suicide is a major public health problem in Australia, accounting for 22% of suicides in 1995. Despite the introduction of catalytic converters and the 1986 reduction in CO exhaust limits, motor vehicle exhaust gas suicides have increased in number, rate and as a proportion of total suicides since 1986. Hospitalisations, however, have doubled, suggesting an increase in failed attempts, and the rate curve for successful suicides also appears to be flattening in the 1990s. In 1995, 43% of registered Australian motor vehicles were manufactured in 1986 or later.2 If exhaust gas suicide had been made impossible by catalytic converters and the 1986 reduced CO emission standard of 9.3 g/km, then rates for such suicides should have reduced from 2.08 to about 1.19 per 100 000 population between 1985 and 1995 (assuming a similar distribution of vehicles to that of the Australian fleet and an unchanged number of attempts). In fact, rates per 100 000 population have been about 2.5 for the past five years and peaked at 2.85 in 1995. It is clear from our investigation of the sample from the Victorian Coroner's files that vehicles manufactured since 1986 have been used in exhaust gas suicides. Our finding that there was no difference in median COHb levels between victims who used vehicles with and without catalytic converters is consistent with the results of a New South Wales study.7 Given that CO emissions from vehicles with catalytic converters are lower, it can be deduced that time (and possibly other factors) need further investigation. The few overseas studies which have examined the relationship between suicides and motor vehicle exhaust gas have found that imposing emission controls reduces the incidence of such suicides.8-10 Vehicle emission limits for CO in the US have been lower than those in Australia, being at our 1986 limit (9.3 g/km) as early as 1975 and at just under our 1997 limit (2.1 g/km) in 1981.11 Thus, US trends should shed some light on the Australian situation, especially as the test conditions are similar. However, it should be noted that the average age of vehicles in the US is seven years, compared with 11 years in Australia, which suggests that there would be a longer lag time for exhaust emission changes to affect suicide rates in Australia. Motor vehicle exhaust gas is a less popular method of suicide in the United States than in Australia (1991 rates per 100 000 population being 0.73, compared with 2.78 for Australia).12 Data available for the US to 1991 show a decline in the exhaust gas suicide rate from the years 1963 to 1979, an increase from 1981 to 1987, followed by a decline to below the pre-1982 rates. Exhaust gas suicides in the US have decreased from 8.9% of suicides in 1970 to 7.4% in 1980 and 5.6% in 1991.8,12 Despite some conflicting evidence in Australia and the US as to the reductions in CO exhaust emission levels ne cessary for influencing exhaust gas suicide rates, these emission reductions do not appear to have produced the success suggested by early reports in the international literature.8-10 There are a variety of possible explanations for this. Firstly, exhaust gas suicides usually involve a hose or pipe being used to feed exhaust gas from an idling vehicle into the sealed interior of a vehicle. Clearly, CO emission levels set for environmental reasons may not be particularly relevant in this situation, and if suicides are to be prevented it would be more appropriate to set CO emission limits in relation to each vehicle's cabin volume. Further, testing vehicles for compliance with environmental standards involves three phases, none of which involve engine idling (during which CO emission could be higher) only. Secondly, CO emissions from vehicles with catalytic converters may exceed the legislated limit. Specific examples are: the engine idles from a cold start, with a delay of 1.5-3 minutes before the catalytic converter has warmed up and is operating efficiently (as blood COHb concentration rises most rapidly when first exposed to CO the initial absorption rate would be particularly high3 ); the condition of the catalytic converter has deteriorated or the engine may require tuning (under ADR 37-00 a catalytic converter is required to operate effectively for 80 000 km or five years, whichever occurs first); and for reasons that are unclear, the pollution performance of 4-9-year-old cars has been found to deteriorate faster than that of older cars.13 A 1989 US report noted that, even with reduced CO emission limits and catalytic converters, it is still possible to use car exhaust for suicide.10 If exposure is prolonged, residual CO content would eventually cause death, or suffocation might occur. Also, destruction of the engine management system, by the use of leaded petrol and neglect, or physical disconnection of the engine management system, could increase the CO content, and thus the lethality of this method for suicide.8 Further research needs to be undertaken in this technically complex area. A study of the vehicles used for unsuccessful exhaust gas suicide attempts and of other factors contributing to their failure would assist in understanding the relationship between vehicles and exhaust gas suicides. New regulations in Australia have not yet reduced suicides from motor vehicle exhaust gas. There is a need to monitor the situation, especially in the light of the 1997 reduction in CO to 2.1 g/km, and to review the regulations, vehicle design and testing methods. Acknowledgments The study was funded by the Victorian Health Promotion Foundation through its funding of the Victorian Injury Surveillance System, a project of Monash University Accident Research Centre. We thank the Victorian State Coroner's Office for providing access to relevant records, Associate Professor David Ranson (Victorian Institute of Forensic Medicine), David Lester (Richard Stockton College of New Jersey), Jerry Moller and Stan Bordeaux (Australian Institute of Health and Welfare, National Injury Surveillance Unit) for providing data, Christine Chesterman and Voula Stathakis (Monash University Accident Research Centre) for assisting with data collection and analysis, respectively, and Dr Ella Sugo (formerly of the NSW Institute of Forensic Medicine), Brian Hobsbawn (Environment Australia) and Jerry Moller for providing valuable comment. References Lester D. Car ownership and suicide by car exhaust in nations of the world. Percept Motor Skills 1994; 79: 898. Australian Bureau of Statistics. May 1995, Motor Vehicle Census. Canberra: ABS, 1996. (Catalogue No. 9309.0.) Ernsting J, King P. Aviation medicine. 2nd ed. London: Butterworths, 1988. Willis Hurst J, Schlant R, Rackley C, et al. The heart. 7th ed. New York: McGraw-Hill, 1990. Smith JS, Brandon S. Morbidity from acute carbon monoxide poisoning at three-year follow-up. BMJ 1973; 1: 318-321. Unnatural deaths, 1993/94. Melbourne: Victorian State Coroner's Office, December 1995. Sugo E, Duflou J, Sercombe J, Brown J. Suicidal inhalation of carbon monoxide -- a reappraisal of variables affecting lethal levels. Paper presented at the Annual Scientific Meeting of the Royal College of Pathologists of Australasia;1996 Sep 16-19; Sydney. Sydney: The College, 1996. Lester D. Changing rates of suicide by car exhaust in men and women in the United States after car exhaust was detoxified. Crisis 1989; 10: 164-168. Clarke R, Lester D. Toxicity of car exhausts and opportunity for suicide: comparison between Britain and the USA. J Epidemiol Community Health 1987; 41: 114-120. Lester D, Abe K. Car availability, exhaust toxicity and suicide. Ann Clin Psychiatry 1989; 1: 247-250. Code of Federal Regulations. Title 40: Protection of environment. Part 86 -- control of air pollution from new and in-use motor vehicles and new and in-use motor vehicle engines: certification and test procedures. Washington, DC: Office of the Federal Register National Archives and Records Administration, 1997. Centers for Disease Control and Prevention, National Center for Health Statistics. Vital statistics of the US. Vol. II. Mortality. Part A. Washington: Public Health Service, May 1996. Federal Office of Road Safety. Motor vehicle pollution in Australia. Report on the national in-service vehicle emission study. Canberra: AGPS, 1996. (Received 18 Mar, accepted 27 Sep, 1997) Authors' details Monash University Accident Research Centre, Melbourne, VIC. Virginia H Routley, BEc, GradDipSocStats, Research Fellow; Joan Ozanne-Smith, MB BS, MPH, Professorial Fellow. No reprints will be available. Correspondence: Ms V H Routley, Monash University Accident Research Centre, Wellington Road, Clayton, VIC 3168. Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/>

Virginia H Routley · Joan Ozanne-Smith

Out of the blue and into the pink A new litmus test for chlorine gas exposure MJA 1997; 167: 651 To the Editor: A 40-year-old man arrived at the emergency department by ambulance in respiratory distress. In his duties as a hotel maintenance worker, he had been mixing swimming pool chemicals in a dark, confined space. Inadvertently, he had mixed liquid pool "chlorine" (sodium hypochlorite) with a hydrochloric acid solution, forming an irritating yellow-green gas. Despite a brief exposure, he rapidly developed eye irritation, burning in his oropharynx, cough and chest pain. He noticed that the keys in his pocket had turned a dull colour. On arrival, about 20 minutes after the exposure, he had an irritating cough, but his vital signs were normal, oxygen saturation was 99%, and his chest was clear to auscultation. His clothing smelt of chlorine and was removed to prevent skin irritation. On removing his white overalls, it was noticed that his blue underpants had changed colour to a pink-mauve hue. Although he suffered acute embarrassment, he developed no acute clinical or radiographic signs and was discharged well after several hours' observation. Chlorine gas exposure is not an uncommon hazard of mixing household cleaners or pool chemicals. The addition of an acid to a chloride-containing base releases chlorine gas in an exothermic reaction. Chlorine gas is highly water soluble and on moist surfaces is transformed into hydrochloric acid and an oxygen radical. This mechanism explains the clinical manifestations, with the hydrochloric acid causing immediate irritation to mucosal surfaces, leading to lacrimation, burning sensations and cough. These symptoms usually serve as a warning to the victim to move away from the gas to prevent the more serious sequelae of laryngeal oedema, bronchospasm and adult respiratory distress syndrome. Presumably in this case, the elaboration of acid in the sweaty confines of his true-blue Y-fronts mimicked the classic pH indicator reaction of litmus paper. Perhaps he should have worn his underpants on the outside! Tim C Green Staff Specialist, Emergency Department, Royal Prince Alfred Hospital Missenden Road, Camperdown, NSW 2050. E-mail: timgreenATmpx.com.au Reference: Hoffman RS. Toxic inhalations. In: Rosen P, Barkin R, et al., editors. Emergency medicine -- concepts and clinical practice. 3rd ed. 1992: 2673-2682. - ©MJA 1997 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Tim C Green

"Hale-Bopp" and "Knocking on Heaven's Gate" Hits of the Net, 1997 MJA 1997; 167: 654 "If anyone comes to Me and does not hate his father and mother and his wife and children and brothers and sisters -- and even his own life also -- he cannot be My disciple". Luke 14:261 To the Editor: This Christmas, as we renew old family quarrels, we should remember we are celebrating the birth of Christ, who, according to the Heaven's Gate cult, was the first visitor from TELAH -- The Evolutionary Level Above Human.1 On 22 March 1997, when the Hale-Bopp comet was nearest to Earth, 39 members of this cult left earth to link up with the comet's "companion spaceship" bound for TELAH,2 wearing black Nike sneakers. Their transport to TELAH began with deliberate self-poisoning. Although we previously found no relationship between self-poisoning and celestial or occult events,3 this event combined both and suggested that we might have overlooked a synergistic mechanism. We also examined the possibility that traffic was going in the opposite direction that day, with ancient astronauts escaping their spaceship to appear on earth as newborn babies. We used two databases to test our hypothesis: a register of births in the Canberra Hospital (which we felt would closely resemble the sterile environment of a spaceship) and the Hunter Area Toxicology Service database of presentations to hospital with self-poisoning in the Lower Hunter Valley of New South Wales. To examine for evidence of massive successful and attempted soul migrations, we compared the number of births and self-poisonings between 21 and 23 March with those for the rest of the month. There did not appear to be any significant surge in self-poisonings or births at this time. On those three days, there were eight self-poisonings, compared with 51 on all the other days in March (P = 0.24, Mann-Whitney test), and 13 births compared with 141 (P = 0.61). However, we did note a surprisingly strong correlation between self-poisonings and the Nike share price4 (P = 0.005, Spearman) (Figure). In the three months after the Heaven's Gate tragedy, the share price of Nike fell by 20%, despite a 15% increase in the market index and a 28% increase in sales.4 This could either be a suicide prevention strategy or evidence that people are reducing their Nike stocks to invest in futures. When surfing the Internet, it is quickly apparent that data-dredging is not confined to medicine and there is no statistical refereeing. Significance can be found everywhere on the Net: a place to publish and perish. Nicholas A Buckley Visiting Fellow,National Centre for Epidemiology and Population Health The Australian National University, Canberra, ACT 0200 E-mail: mdnabATcc.newcastle.edu.au Janelle A McDonald Obstetric Registrar, National Centre for Epidemiology and Population Health The Australian National University, Canberra, ACT 0200 Do, Ti, et al. How and when Heaven's Gate may be entered (The door to the Physical Kingdom Level Above Human). Phoenix (Ariz): TELAH Services, 1997. On the Internet: http://www5.zdnet.com/yil/higher/heavensgate/ http://www.neosoft.com/~cshramek/comet.htm Buckley NA, Whyte IM, Dawson AH. There are days . . . and moons. Self-poisoning is not lunacy. Med J Aust 1993; 159 (11/12): 786-789. http://quote.yahoo.com/ - ©MJA 1997 Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au>". <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Nicholas A Buckley · Janelle A McDonald

A model for the management of self-poisoning Ian M Whyte, Andrew H Dawson, Nicholas A Buckley, Gregory L Carter and Catherine M Levey Readers may print a single copy for personal use. No further reproduction or distribution of the articles should proceed without the permission of the publisher. For permission, contact the Australasian Medical Publishing Company Journalists are welcome to write news stories based on what they read here, but should acknowledge their source as "an article published on the Internet by The Medical Journal of Australia <http://www.mja.com.au/>". Abstract - Introduction - Service structure - Philosophy and strategies - Nursing perspective - Psychiatric perspective - Medical perspective - Outcomes and resource use - Discussion - Acknowledgements - References - Authors' details - ©MJA1997 Abstract Objective: To describe the development and activity of a multidisciplinary service to manage self-poisoning. Design: Descriptive, comparative study with prospective data collection. Setting: Regional toxicology treatment centre in the Hunter area of New South Wales (NSW) with primary and secondary referral service to 385 000 people and tertiary referral service to a further 100 000. Patients: All patients (1987-1995) with poisoning or envenomation presenting to the Hunter Area Toxicology Service (HATS). Main outcome measures: Average length of stay for HATS compared with national and NSW hospitals; mortality data for HATS compared with NSW. Results: Average length of stay for HATS was 0.53-1.22 days shorter than for all Australian hospitals, potentially saving 518 bed-days, valued at $468 000 per year. Average length of stay was 0.94-3.39 days shorter than for all NSW hospitals, saving 1470 bed-days at $1.4 million per year. Inpatient mortality (0.2%; 95% confidence interval, 0.0-1.1) was not significantly different from NSW (0.5%; 95% CI, 0.2-0.8). Standardised mortality ratios showed no greater all-cause suicide mortality. Conclusions: In our centralised model for managing self-poisoning, all toxicology patients in an area health service are diverted to one hospital, where all patients with deliberate self-poisoning are admitted under the one multidisciplinary team, and all receive psychiatric assessment. This model has substantially reduced bed stay, with considerable savings to the Hunter Area Health Service manifested as an increase in beds available for other purposes. MJA 1997; 167: 142-146 Introduction Estimates of admissions for deliberate self-poisoning vary from 1%1 up to 5%2 of public hospital admissions. More than 50% of these admissions occur between 6 pm and 2 am.3 Deliberate self-poisoning (including carbon monoxide) is the cause of death in 42% of suicides.4 With a few exceptions, deliberate self-poisoning is managed on an ad-hoc basis in Australian hospitals. Commonly, the patient is managed in the emergency department and, if required, admission occurs under the general physician of the day or under the specialty which best corresponds to the patient's toxicological problem. Other models include medical management for most patients occurring entirely within the emergency department/intensive care axis. In one centre, 30% of patients with deliberate self-poisoning were not formally admitted.5 In many centres, expertise in toxicology comes from outside the service providing the patient care (e.g., from Poisons Information Centres). In these models of management, not every patient with deliberate self-poisoning receives formal psychiatric assessment. Despite evidence that psychiatric intervention after parasuicide is worthwhile,6 psychiatric resources are commonly concentrated on those patients who require admission and those who have the most medically severe poisoning.7 However, significant suicidal risk is present for many patients with toxicologically "trivial" poisonings. Service structure In 1986 the Department of Clinical Pharmacology, then located at the Royal Newcastle Hospital, was requested to manage deliberate self-poisoning and other toxicology patients. The Hunter Area Toxicology Service (HATS) was established jointly by the Department of Clinical Toxicology and Pharmacology and the Department of Liaison Psychiatry in January 1987. The only increase in staff was one registrar position in clinical pharmacology. All deliberate self-poisoning patients are formally admitted under the HATS clinical toxicologist, who retains primary responsibility for care during the whole admission. A toxicology data collection form was developed which is also the formal admission record. The psychiatry team assess all patients with deliberate self-poisoning and, on request, other poisonings. Referral to the drug and alcohol service occurs as necessary. The patient is determined as medically fit for discharge by the toxicologist and the decision on appropriate discharge destination is made by the psychiatrist. Medical follow-up, when required, is the responsibility of the toxicologist. A relational database for collecting data on poisoned patients4 was written (by I M W) in late 1986. The complexity of this database has progressively increased and an extensive psychiatric component (written by G L C) became operational in January 1996. HATS was transferred to the Newcastle Mater Misericordiae Hospital in 1991 and took on an Area role (population, 385 000). All poisoning cases are transferred, either directly or after assessment at a closer hospital, to the Newcastle Mater Misericordiae Hospital unless they are too ill. If they are admitted to another hospital, they are admitted under the care of HATS. In practice, this relates to critically ill patients who are admitted to the intensive care unit at the presenting hospital under the care of the toxicologist from HATS, and discharged directly from that unit or transferred to the Newcastle Mater Misericordiae Hospital if they need more inpatient care after their intensive care stay. HATS provides a 24-hour telephone consulting service for the Upper and Lower Hunter Areas (population, 100 000) and a tertiary referral service when required. The clinical pathway for this managed care is shown in Figure 1. HATS medical management is provided by a full time equivalent clinical toxicologist (currently two clinical pharmacologists) and a registrar in clinical toxicology. The after hours service is provided by the two clinical pharmacologists with the addition of another clinical pharmacologist and a drug and alcohol specialist with an interest in toxicology. Every toxicology admission is seen by the medical team (at least once a day), seven days a week. HATS psychiatric care is provided by a psychiatrist, a psychiatry registrar and a clinical nurse consultant in psychiatry. An after hours service is provided by part of an area roster of psychiatry registrars and four to six "second on call" psychiatrists. Every deliberate self-poisoning admission is seen by the psychiatry team (at least once a day), seven days a week. Even when the patient is consciously or cognitively impaired, our practice is to begin the psychiatric assessment by obtaining a collateral history from family/friends and health care workers before proceeding with individual psychiatric assessment. If the patient presents with a toxicologically trivial poisoning after 5 pm or on weekends (which would allow discharge before the routine morning psychiatric review) then the psychiatric registrar on call will come in to do the assessment and decide on appropriate discharge destination. Philosophy and strategies HATS was established with the premise that deliberate self-poisoning is a presenting symptom for an underlying psychiatric disorder, personality disorder or psychosocial problem that requires assessment and intervention. A distinction is made between "drug overdose" (exposure to an amount of drug or toxin sufficient to cause harm) and the more inclusive term "deliberate self-poisoning", which also includes toxicologically trivial exposures. All admissions are formally discussed at a weekly multidisciplinary meeting where medical and psychiatric management is reviewed. When appropriate, individualised management plans are discussed for patients who have frequent presentations. Nursing perspective Nursing care of deliberate self-poisoning patients uses a combined medical and behavioural model. The staff recognise that patients with deliberate self-poisoning are entitled to a legitimate "sick role"8 and use a non-judgemental approach to patients and their relatives. Retention of patients for the full duration of treatment can be increased by emphasising the need for medical review and treating deliberate self-poisoning patients in a similar manner to other medical patients. In the acute phase of the admission, patients are kept in hospital pyjamas and their street clothes removed. Patients with catheters or intravenous cannulas often have these devices kept in situ until their mental state is assessed and their discharge destination is determined by the psychiatric team. The involvement of family and friends in helping to orientate and support the patient can lessen the nursing burden and improve compliance. Psychiatric perspective Psychiatric care of deliberate self-poisoning patients is aimed at maintaining the safety of the patient (and staff), enhancing compliance with decontamination and other medical treatment, psychological support, the initiation of treatment for specific indications (e.g., delirium, psychosis and relationship problems), and coordination of psychiatric follow-up. The incorporation of a psychiatry team in HATS allows for very early intervention in deliberate self-poisoning, in contrast to consulting the psychiatrist after completion of medical management. Medical perspective The primary aim in the treatment of poisoned patients is to reduce mortality and early and late morbidity. The secondary aim of treatment is to reduce hospital stay and use hospital resources efficiently. This is accomplished by an active education program9 focused on evidence-based management, good supportive care and actively discouraging punitive medical procedures. Outcomes and resource use The NSW Health Department Inpatient Statistics Collection uses average length of stay (with a minimum bed stay for a formal admission defined as one day). Examination of medical records data for patients with self-poisoning (ICD-9-CM10 codes E950-E959) admitted to the Royal Newcastle Hospital in 1985 and 1986 showed an average length of stay of 3.88 days. For 1987, when HATS began to operate, the average length of stay for this group of patients had decreased to 2.75 days and for 1988 to 1.4 days. In 1995 there were 736 admissions to HATS (see Box 1). The median (range) hospital stay is calculated because the data are not normally distributed. The lower quartile is at 10.5 hours and the upper quartile at 27.5 hours. The distribution of hospital stay for deliberate self-poisoning patients is shown in Figure 2. In 1994-1995, for all hospitals with an emergency department in the Greater Newcastle area, deliberate self-poisoning comprised 1.2% of medical admissions; most presented to Newcastle Mater Misericordiae Hospital, where they comprised 7.3% of medical admissions. Of the 520 deliberate self-poisoning admissions who received formal psychiatric assessment, 492 (94.6%) had had one or more formal diagnoses11 made of psychiatric disorder, personality disorder or other condition ("V" codes11). Average length of stay data for HATS compared with national data and all NSW public hospitals are shown in Boxes 2 and 3, respectively. Box 2 compares data derived from the HATS database for 1991-1994 with national data for 1992 (the most recent year available). Box 3 presents data from the NSW Health Department Inpatient Statistics Collection (1994-1995), and compares deliberate self-poisoning admissions to Newcastle Mater Misericordiae Hospital with the mean for all public hospitals in NSW. The data from Newcastle Mater Misericordiae Hospital in Box 3 are not derived from the HATS database, but rather from independent coding by the Medical Records Department of the Newcastle Mater Misericordiae Hospital according to ICD-9-CM.10 Both comparisons show a substantial reduction in bed stay for HATS. Since those patients not formally admitted at other hospitals are likely to be short stay presentations and thus not reported in the Inpatient Statistics Collection, we further analysed HATS data for 1993-1995. For all admissions average length of stay was 1.5 days; for all admissions with a hospital stay greater than 12 hours (72.6% of admissions) average length of stay was 1.69 days; for all admissions that required intensive care admission (16.8%), average length of stay was 2.59 days. There has been no evidence that reduced bed stay has compromised patient care, as mortality from deliberate self-poisoning during this period (1987-1995) has been 0.6% (24 deaths in 3856 deliberate self-poisoning admissions; 95% CI, 0.4-0.9). Most of these patients had an out-of-hospital cardiac arrest and death was inevitable on presentation.4 NSW Health Department data for 1992 (the most recent year for which death data are available) show 13 inpatient deaths in 2876 admissions in NSW (0.5%; 95% CI, 0.2-0.8). HATS data for 1992 show one inpatient death in 512 deliberate self-poisoning admissions (0.2%; 95% CI, 0.0-1.1). These proportions are not significantly different (chi-squared = 2.04; P = 0.36). Standardised mortality ratios for suicide in NSW show the Hunter Area has no greater all-cause suicide mortality.13 HATS' prospective data collection on all presentations in a defined population is a very powerful tool for observational research. We have been able to identify public health issues related to patterns of drug use,14,15 relative toxicity of drugs within classes16-18 and the impact of safety packaging of medications.19 The NSW Health Department, as part of its health outcomes strategy, has provided funds to HATS to develop the management model (and the database) so that it can be trialled at other centres in NSW. Discussion There are difficulties in comparing data collected by clinicians with a particular interest in a group of patients and national data derived from ICD-9 coding from all hospitals in Australia. The main difficulty is the potential for ascertainment bias. For example, it is possible the national data contain significant numbers of patients without true deliberate self-poisoning, who have a longer length of stay. This may make our comparisons less robust. However, the data for NMMH in Box 3 are the official data requested by the NSW Department of Health for inclusion in the NSW Inpatient Statistics Collection and are thus directly comparable to data from other NSW public hospitals. It could be argued that shorter length of stay in the Hunter is due to our policy of admitting all patients with deliberate self-poisoning regardless of severity. However, the greatest difference in average length of stay occurs in those patients with complications or comorbidities (Boxes 2 and 3), who require admission under any policy. Figure 2 shows that 90% of all our patients stay in hospital for less than 50 hours, which is less than the average length of stay for uncomplicated poisoning in NSW public hospitals (Box 3). In addition, HATS bed stay for all admissions (complicated and uncomplicated) after excluding those admitted for less than 12 hours (27.3% of presentations) is still shorter than the average length of stay for uncomplicated admissions to all NSW hospitals. The average length of stay for HATS admissions requiring intensive care is more than two days shorter than the average length of stay for all complicated admissions to NSW hospitals. The model of management of self-poisoning described in this article is, we believe, unique in Australia. The differences we have identified in this model are: all toxicology presentations in one Area Health Service are diverted (by ambulance services and emergency departments) to one hospital all deliberate self-poisoning presentations are admitted all admissions are to one team the team is multidisciplinary, with medical, psychiatric, drug and alcohol, and nursing participation all deliberate self-poisoning admissions receive psychiatric assessment a 24-hour service for management and advice is provided. We argue that all patients who present with deliberate self-poisoning should be admitted for several reasons: deliberate self-poisoning is a presenting symptom for another problem that requires assessment and intervention most deliberate self-poisoning admissions (94.6%) have a diagnosable psychiatric disorder, personality disorder or other psychiatric condition formal admission facilitates more efficient and effective assessment and management of both medical and psychiatric issues as more than half the presentations occur after hours, overnight admission is required to ensure adequate psychiatric assessment. This model has resulted in a substantial and significant reduction in bed stay, which increases beds available for other purposes in the Area. There are two ways of calculating the monetary cost if funding were on a diagnosis-related group (DRG) basis. The first is to multiply the bed-days saved by the DRG cost of a bed-day, as in Box 2 and Box 3. The second is to assume the saved beds will be occupied by patients attracting further DRG funding. Assigning a monetary value to this is not possible. It is clear, however, that based on DRG funding these saved bed-days are worth more to the Area than the cost of running the service. The reduction in bed stay has not been accompanied by a worsening in outcome, as defined by in-hospital mortality from deliberate self-poisoning or standardised mortality ratios for all-cause suicide. While the number of admissions to HATS in 1992 appears disproportionate, it is consistent with the proportion of admissions to other major hospitals1,2 and reflects our policy of admitting all patients who present with deliberate self-poisoning. It appears likely the Department of Health figures for admissions significantly underestimate the number of presentations for deliberate self-poisoning to NSW hospitals. If so, while the magnitude of the saving per admission may be uncertain, on a State-wide basis the potential savings from implementing our model are even greater. Without further data, determining the reasons for the shorter average length of stay is not possible, but anecdotal comparisons with other hospitals suggest the following possibilities: centralised, evidence-based management of specific poisonings resulting in earlier recognition of non-toxic or minimally toxic exposure more efficient gastrointestinal decontamination better management of significant toxic exposure more efficient use of psychiatric assessment, aftercare and discharge planning increased involvement of nursing staff in a multidisciplinary approach. Our current model of management has evolved using the skills and experience of those interested in poisoning in Newcastle. The only new position created was the registrar position in clinical pharmacology. We do not believe, however, that replicating the model or its outcomes is dependent on replicating our subspecialty mix. Nevertheless, the identification of a team to manage poisoning is crucial. In many health areas the emergency physicians may be the logical choice for such a team. This would require an extension of admitting rights into the general hospital or a collaborative venture with an identifiable medical team. A specific group of psychiatrists is also required. We believe that Area Health Services should consolidate acute toxicology services. A potential disadvantage of consolidation is loss of skills in the management of toxicological problems in other hospitals in the Area. This could be offset by making the service part of registrar and nursing training rotations. The advantages of consolidation include: individualising patient care continuity of care a better learning curve via greater experience training, education and research. The efficiencies of this model are a product of the reorganisation of largely existing resources to provide a multidisciplinary team approach to the management of poisoned patients. The provision of care is based on a philosophy that these patients are entitled to a legitimate sick role. The major stumbling block to establishing a similar dedicated service is in making the decision to reorganise existing services. As House et al. state, after reviewing services in the United Kingdom, "there is much to recommend in clinical diversity, but nothing to recommend [in] unplanned and incoordinated service provision".6 Acknowledgements We would like to acknowledge the support of nursing staff in the Intensive Care Unit, the Emergency Department and Ward 5E at the Newcastle Mater Misericordiae Hospital. The Hunter Area Toxicology Service has also received considerable support from the Mental Health Epidemiology Group (NSW Department of Health) and the Chief Executive Officer of the Hunter Area Health Service, Dr Timothy Smyth. Some of the later development of this service was supported by a NSW Health Department Health Outcomes grant and a grant from the Hunter Area Health Service. References Pond SM. Prescription for poisoning. Med J Aust 1995; 162: 174-175. McGrath J. A survey of deliberate self-poisoning. Med J Aust 1989; 150: 317-322. Buckley NA, Whyte IM, Dawson AH. There are days . . . and moons. Self-poisoning is not lunacy [letter]. Med J Aust 1993; 159: 786-789. Buckley NA, Whyte IM, Dawson AH, et al. Self-poisoning in Newcastle, 1987-1992. Med J Aust 1995; 162: 190-193. Davis AT, Kosky RJ. Attempted suicide in Adelaide and Perth: changing rates for males and females, 1971-1987. Med J Aust 1991; 154: 666-685. House A, Owens D, Storer D. Psycho-social intervention following attempted suicide: is there a case for better services? Int Rev Psychiatry 1992; 4: 15-22. Tengel E, Cook NG, Kreeger IS. Attempted suicide. London: Chapman & Hall, 1958. Parsons T. The social system. London: Routledge and Kegan Paul, 1951. Buckley NA, Dawson AH, Whyte IM. HyperTox -- a hypertext teaching program in toxicology. < http://www.ozemail.com.au/~ouad/toxi0002.html > > World Health Organisation: International Classification of Disease ICD-9. Clinical modification, 1978. Geneva: WHO, 1992. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994. Manual of resource items and their associated costs for use in submissions to the Pharmaceutical Benefits Advisory Committee involving economic analyses. Australian Government Publishing Service, Canberra, 1992. Stewart G, Chipps JA, Sayer G. Suicide mortality in NSW local government areas. NSW Public Health Bull 1995; 7: 1-10. Smith AJ, Whyte IM. New drugs for old: an issue for debate? Med J Aust 1988; 149: 581-582. Dawson AH, Whyte IM. Compound analgesics [letter]. Med J Aust 1990; 152: 334. Buckley NA, Dawson AH, Whyte IM, Henry DA. Greater toxicity in overdose of dothiepin than of other tricyclic antidepressants. Lancet 1994; 343: 159-162. Buckley NA, Dawson AH, Whyte IM, O'Connell DL. Relative toxicity of benzo diazepines in overdose. BMJ 1995; 310: 219-221. Buckley NA, Whyte IM, Dawson AH. Cardiotoxicity more common in thioridazine overdose than with other neuroleptics. J Toxicol Clin Toxicol 1995; 33: 199-204. Buckley NA, Newby DA, Dawson AH, Whyte IM. The effect of the introduction of safety packaging for carbamazepine on toxicity in overdose in adults. Pharmacoepidemiol Drug Safety 1995; 4: 351-354. (Received 26 Aug 1996, accepted 3 Apr 1997) Authors' details Newcastle Mater Misericordiae Hospital, Newcastle, NSW. Ian M Whyte, FRACP, Senior Staff Specialist and Director, Department of Clinical Toxicology and Pharmacology. Andrew H Dawson, FRCP, FRACP, Staff Specialist, Department of Clinical Toxicology and Pharmacology. Gregory L Carter, FRANZCP, Senior Staff Specialist, Department of Liaison Psychiatry. Catherine M Levey, RN, ICUCert, Clinical Nurse Specialist, Intensive Care Unit. Discipline of Clinical Pharmacology, University of Newcastle, Newcastle, NSW. Nicholas A Buckley, FRACP, Lecturer. Reprints: Dr I M Whyte, Department of Clinical Toxicology and Pharmacology, Newcastle Mater Misericordiae Hospital, Locked Bag 7, Hunter Regional Mail Centre, NSW 2310. E-mail: mdimw@cc.newcastle.edu.au ©MJA 1997 <URL: http://www.mja.com.au/> © 1997 Medical Journal of Australia.

Ian M Whyte · Andrew H Dawson · Nicholas A Buckley · Gregory L Carter · Cathterine M Levey