Search

ABSTRACTWe report a case of a 19-year-old woman who ingested Digitalis purpurea leaves as a suicide attempt. She developed gastro-intestinal symptoms, loss of colour vision, cardiac conduction disturbances as well as an elevated serum potassium. Treatment was initiated in analogy to medicinal digoxin poisoning by means of digoxin-specific Fab-fragments with a good effect. However during the further course we faced difficulties of prolonged intestinal absorption and inability to estimate the ingested dose or half-life of the vegetal cardiac glycoside compounds. To prevent further absorption and interrupt enterohepatic recycling, multi-dose activated charcoal was administered. Because of a relapse of cardiac conduction disturbances and hyperkalemia, two supplementary doses of Fab-fragments were given, up to a total dose of nineteen vials (one vial containing 40 mg). The important diagnostic and therapeutic differences of vegetal digitalis intoxication as compared to medicinal intoxication and the applicability of existing guidelines on medicinal digitalis intoxication in the light of these differences will be discussed here.

ABSTRACTObjectives: To test the feasibility of an evidence-based protocol for procedural sedation in adults at our emergency department, using a mixture of ketamine and propofol (‘ketofol’) in a 1 to 4 ratio. We hypothesize that the protocol is safe and effective and can facilitate procedural sedation.Methods: During 14 months, adults in need of procedural sedation at our university hospital emergency department were included in a prospective convenience sample study. Patients with important comorbidity were discussed with the anaesthesiology department for feasibility of sedation in the emergency department setting. Outcome measures were procedural success, respiratory and hemodynamic events, vomiting, agitation or hallucinations, recall and physician’s satisfaction.Results: Sixty-one patients between 18 and 89 years were included. All but one procedure were successful. Six respiratory events were registered in 6 patients (9.8%). These consisted of airway obstruction alleviated by airway repositioning and without influence on vital signs except for one brief episode of desaturation. Neither hemodynamic events nor vomiting were reported. Five patients (8.2%) experienced pleasant hallucinations and one patient (1.6%) became agitated upon awakening but recovered rapidly without medication. Three patients (4.9%) had recall and physician satisfaction rate was 93.4%.Conclusion: A feasibility trial of an implemented protocol for ketofol procedural sedation in adults showed only minor respiratory events, a low incidence of agitation or hallucinations, minimal recall and a high success and physician satisfaction rate. Despite a non-consecutive and limited sample used, ketofol in a 1 to 4 ratio appears safe and effective for use in the emergency department.

Objectives: This study evaluates the impact of the Belgian Poison Centre (BPC) on national healthcare expenses for calls from the public for unintentional poisonings. Methods: The probability of either calling the BPC, consulting a general practitioner (GP) or consulting an emergency department (ED) was examined in a telephone survey (February–March 2016). Callers were asked what they would have done in case of unavailability of the BPC. The proportion and cost for ED-ambulatory care, ED 24-h observation or hospitalisation were calculated from individual invoices. A cost–benefit analysis was performed. Results: Unintentional cases (n= 485) from 1045 calls to the BPC were included. After having called the BPC, 92.1% did not seek further medical help, 4.2% consulted a GP and 3.7% went to an ED. In the absence of the BPC, 13.8% would not have sought any further help, 49.3% would have consulted a GP and 36.9% would have gone to the hospital. The cost–benefit ratio of the availability of the BPC as versus its absence was estimated at 5.70. Conclusions: Financial savings can be made if people first call the BPC for unintentional poisonings.

In the literature, possible systemic effects on health of inhalation or ingestion of white spirit are well described. Only a few case reports discuss the toxic skin effects that can occur following massive ingestion. Ingestion of large amounts of white spirit produces a watery diarrhoea with a high concentration of white spirit, resulting in perineal skin burns when there is prolonged contact. We describe a patient who developed partial thickness perineal skin burns after ingestion of white spirit and review the literature. The present data indicate that conservative therapy of the skin burns is recommended.

We describe a nonlethal, delayed onset case of combined acute inhalation of hydrofluoric acid (HFA) and nitric acid (NA) together with a review of the literature. Our patient was exposed to fumes of a 12% HFA and 22% NA solution in a closed environment and suffered during several months after the incident from exertional dyspnoea but recovered completely. Since HFA and NA are dangerous and widely used substances, preparedness for exposure is mandatory. After inhalational exposure, the principles of decontamination with attention to treatment of the skin for HFA burns together with general medical incident management should be applied. The severity of combined NA and HFA intoxication depends on the concentration, the nature of the contact and the duration of exposure but other factors may also be involved. Therapy resistant hypoxia and death have been reported in the literature. Inhalation injury from HFA alone is rare but systemic toxicity should be anticipated. Calcium is advocated as the cornerstone of local and systemic therapy. NA inhalation alone is very rare and causes heavy pulmonary irritation. Massive pulmonary secretions seem a sign of very severe intoxication and treatment appears to be mainly supportive.

Objectives: It is known that tension pneumoperitoneum (TPP) can lead to cardiopulmonary arrest but it does not figure in the advanced life support algorithms. Therefore we discuss a case of TPP together with the literature review of its aetiology and treatment.Patient: We describe an out of hospital cardiac arrest due to a spontaneous TPP secondary to a perforated duodenal ulcer.Conclusion: Emergency personnel should consider the possibility of TPP in a patient with a distended abdomen and a cardiac arrest, even in the absence of known traumatic and iatrogenic causes for TPP. We believe that TPP should be added as a reversible cause for pulseless electrical activity in the resuscitation guidelines.

During ‘I love techno’ (edition 2001), an indoor rave party attended by 37 000 people, data about medical problems (especially drug-related problems) were collected. To place these data in a wider perspective, a similar registration was done during ‘De Nacht’, a traditional New Year's Eve dance party held at the same location and attended by 12 000 people. Furthermore, a prospective study on the time course of the level of consciousness (Glasgow Coma Score) and blood concentrations of illicit drugs, especially gamma-hydroxybutyrate was set up.

High speed and an aggressive style of driving are major risk factors for serious traffic accidents. Consequently, frontline emergency medical services vehicles have an increased collision risk. We report on two studies designed to modify the risk-taking behaviour of emergency medical services drivers. In the first study, we compared the travel intervals for a second tier unit using two different types of vehicles. We found that the replacement of a sports estate by an ambulance, which can be considered more or less as a change from a speedy and aggressive style of driving to a cautious style of driving with respect for the speed limits, resulted in an increase of the travel interval of only 10–20. In the second study we found that the installation of a ‘black box’ in an emergency medical services vehicle, combined with well-defined guidelines for the drivers and a close monitoring system, provides fair but still not optimal results with regard to maximum speed and the occurrence of harsh braking events. Despite some limitations in the study designs, we conclude that for second tier units only a small amount of time is gained by high speed and an aggressive style of driving. Furthermore, we are convinced that a ‘black box’ is a good tool to modify the risk-taking behaviour of emergency medical services drivers.

To assess the availability and use of diagnostic tools, therapeutic equipment and drugs for the prehospital treatment of acute coronary syndromes, cardiopulmonary arrest and other cardiovascular emergencies in Belgian physician-staffed and hospital-based mobile intensive care units.

Tolerance to gamma‐hydroxybutyrate (GHB) has been suggested in illicit users and has been described for the hypnotic effect in the rat. The aim of this study was to investigate whether tolerance is also observed for the EEG effect, and whether the EEG can give insight into the pharmacodynamic aspects of GHB tolerance. In three series of experiments, rats were pre‐treated with either the GHB precursor gamma‐butyrolactone (GBL) or saline intraperitoneally twice daily. In the first series, a reduction in sleeping time was observed in the GBL pre‐treated rats compared with controls. In the second series, a fast infusion of GHB (300 mg kg−1over 5 min) was given after 10 days pre‐treatment. The GHB plasma concentration‐time curves showed a slightly faster decrease in GHB concentration in the GBL pre‐treated rats, suggesting a small induction of the GHB metabolism (Vmax= 2882 ± 457 μg min−1kg−1vs 2205 ± 315 μg min−1kg−1, P<0.01). In contrast to controls, GBL pre‐treated rats did not lose righting reflex. In the third series, a slow infusion of 480 mg kg−1h−1was given after 7 days pre‐treatment, which allowed fitting a sigmoid Emaxmodel to the EEG amplitude versus GHB plasma concentration curve. This showed reduced end‐organ sensitivity to GHB in the GBL pre‐treated rats (EC50 (concentration required to obtain 50% depression of the baseline effect) = 653 ± 183 μg mL−1vs 323 ± 68 μg mL−1, P< 0.001). In conclusion, chronic pre‐treatment with gamma‐butyrolactone in the rat results in a reduced sleeping time and this tolerance is reflected by the EEG. This can mainly be explained by reduced end‐organ sensitivity.

Tolerance to gamma-hydroxybutyrate (GHB) has been suggested in illicit users and has been described for the hypnotic effect in the rat. The aim of this study was to investigate whether tolerance is also observed for the EEG effect, and whether the EEG can give insight into the pharmacodynamic aspects of GHB tolerance. In three series of experiments, rats were pre-treated with either the GHB precursor gamma-butyrolactone (GBL) or saline intraperitoneally twice daily. In the first series, a reduction in sleeping time was observed in the GBL pre-treated rats compared with controls. In the second series, a fast infusion of GHB (300 mg kg−1over 5 min) was given after 10 days pre-treatment. The GHB plasma concentration-time curves showed a slightly faster decrease in GHB concentration in the GBL pre-treated rats, suggesting a small induction of the GHB metabolism (Vmax= 2882 ± 457 μg min−1kg−1vs 2205 ± 315 μg min−1kg−1, P<0.01). In contrast to controls, GBL pre-treated rats did not lose righting reflex. In the third series, a slow infusion of 480 mg kg−1h−1was given after 7 days pre-treatment, which allowed fitting a sigmoid Emaxmodel to the EEG amplitude versus GHB plasma concentration curve. This showed reduced end-organ sensitivity to GHB in the GBL pre-treated rats (EC50 (concentration required to obtain 50% depression of the baseline effect) = 653 ± 183 μg mL−1vs 323 ± 68 μg mL−1, P< 0.001). In conclusion, chronic pre-treatment with gamma-butyrolactone in the rat results in a reduced sleeping time and this tolerance is reflected by the EEG. This can mainly be explained by reduced end-organ sensitivity.

Endotoxemia decreases the dose requirement for anesthetics but no data are available for propofol. A rat model was used in which the influence of endotoxin administration on the pharmacokinetics and pharmacodynamics of propofol was investigated. Chronically instrumented rats were randomly allocated to either a control (n = 9) or an endotoxin (n = 9) group. Six hours after pretreatment with either endotoxin or its solvent, propofol was infused (150 mg · kg⁻¹ · h⁻¹) until isoelectric periods of 5 s or longer were observed in the electroencephalogram. The changes observed in the electroencephalogram were quantified using aperiodic analysis and used as a surrogate measure of hypnosis. The righting reflex served as a clinical measure of hypnosis. The propofol dose needed to reach the electroencephalographic end point in the endotoxin-treated rats was reduced by almost 50% (p &lt; 0.01). This could be attributed to a decrease in propofol clearance and in distribution volume related to the degree of physiologic and metabolic disturbances induced by endotoxin. To investigate changes in end organ sensitivity, the biphasic electroencephalographic effect versus effect-site concentration relationship was studied. This relationship was characterized by descriptors that showed an increased intrinsic efficacy of propofol in the endotoxin group. The effect-site concentration at the return of righting reflex was lower in the endotoxin group. Our study demonstrates that endotoxin-treated animals need a lower dose of propofol to reach the same degree of anesthetic effect which can mainly be attributed to changes in pharmacokinetics. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 92:104–114, 2003

Endotoxemia decreases the dose requirement for anesthetics but no data are available for propofol. A rat model was used in which the influence of endotoxin administration on the pharmacokinetics and pharmacodynamics of propofol was investigated. Chronically instrumented rats were randomly allocated to either a control (n = 9) or an endotoxin (n = 9) group. Six hours after pretreatment with either endotoxin or its solvent, propofol was infused (150 mg · kg−1 · h−1) until isoelectric periods of 5 s or longer were observed in the electroencephalogram. The changes observed in the electroencephalogram were quantified using aperiodic analysis and used as a surrogate measure of hypnosis. The righting reflex served as a clinical measure of hypnosis. The propofol dose needed to reach the electroencephalographic end point in the endotoxin-treated rats was reduced by almost 50% (p < 0.01). This could be attributed to a decrease in propofol clearance and in distribution volume related to the degree of physiologic and metabolic disturbances induced by endotoxin. To investigate changes in end organ sensitivity, the biphasic electroencephalographic effect versus effect-site concentration relationship was studied. This relationship was characterized by descriptors that showed an increased intrinsic efficacy of propofol in the endotoxin group. The effect-site concentration at the return of righting reflex was lower in the endotoxin group. Our study demonstrates that endotoxin-treated animals need a lower dose of propofol to reach the same degree of anesthetic effect which can mainly be attributed to changes in pharmacokinetics.

In view of the potential interest in an objective parameter for the depth of coma in intoxications with the recreational drug gamma-hydroxybutyrate (GHB), we have studied the relationship between the plasma concentrations and the electroencephalographic (EEG) changes induced by GHB in the rat. Fifteen rats randomly received either 150 (n = 3), 200 (n = 6) or 300 mg kg−1(n = 6) GHB over 5 min, followed by a supramaximal dose of 450 mg kg−1over 5 min at the end of the experiment. Plasma concentrations were determined with HPLC. The EEG was continuously recorded and the amplitude in the 15.5–30 Hz frequency band was quantified using aperiodic analysis. The plasma concentration-time profiles were fitted to a two-compartment model with Michaelis-Menten elimination. The pharmacokinetic parameters Vmax, Kmand the apparent volume of distribution (Vd) proved to be independent of the dose and the mean pooled values were Vmax2068 ± 140 μg mL−1kg−1, Km58 ± 16 μg mL−1and Vd 476 ± 12 mL kg−1. The EEG amplitude in the 15.5–30 Hz frequency band displayed a monophasic inhibition and the effect-plasma concentration curve showed hysteresis. This hysteresis between EEG effect and plasma concentrations was minimized by simultaneous calculation of hypothetical effect-site concentrations and fitting the effect vs effect-site concentration curve to a sigmoid inhibitory Emaxmodel. The descriptors of this Emaxmodel (Emax, EC50, ke,0, γ and E0) were independent of the dose with an equilibration half-life t½ke,0of 5.6 ± 0.3 min (mean value of the pooled results of the 5-min treatment groups). To investigate the origin of this hysteresis, a dose of 600 mg kg−1GHB was infused over either 45 or 60 min each in three animals. The hysteresis was much less pronounced with 45 min than with 5 min and was absent with 60-min infusions. This indicated that the hysteresis was due to a distribution delay between the central compartment and the effect site. This study showed that the concentration-effect relationship of GHB could be characterized in individual rats using aperiodic analysis in the 15.5–30 Hz frequency band.

In view of the potential interest in an objective parameter for the depth of coma in intoxications with the recreational drug gamma‐hydroxybutyrate (GHB), we have studied the relationship between the plasma concentrations and the electroencephalographic (EEG) changes induced by GHB in the rat. Fifteen rats randomly received either 150 (n = 3), 200 (n = 6) or 300 mg kg−1(n = 6) GHB over 5 min, followed by a supramaximal dose of 450 mg kg−1over 5 min at the end of the experiment. Plasma concentrations were determined with HPLC. The EEG was continuously recorded and the amplitude in the 15.5–30 Hz frequency band was quantified using aperiodic analysis. The plasma concentration‐time profiles were fitted to a two‐compartment model with Michaelis‐Menten elimination. The pharmacokinetic parameters Vmax, Kmand the apparent volume of distribution (Vd) proved to be independent of the dose and the mean pooled values were Vmax2068 ± 140 μg mL−1kg−1, Km58 ± 16 μg mL−1and Vd 476 ± 12 mL kg−1. The EEG amplitude in the 15.5–30 Hz frequency band displayed a monophasic inhibition and the effect‐plasma concentration curve showed hysteresis. This hysteresis between EEG effect and plasma concentrations was minimized by simultaneous calculation of hypothetical effect‐site concentrations and fitting the effect vs effect‐site concentration curve to a sigmoid inhibitory Emaxmodel. The descriptors of this Emaxmodel (Emax, EC50, ke,0, γ and E0) were independent of the dose with an equilibration half‐life t½ke,0of 5.6 ± 0.3 min (mean value of the pooled results of the 5‐min treatment groups). To investigate the origin of this hysteresis, a dose of 600 mg kg−1GHB was infused over either 45 or 60 min each in three animals. The hysteresis was much less pronounced with 45 min than with 5 min and was absent with 60‐min infusions. This indicated that the hysteresis was due to a distribution delay between the central compartment and the effect site. This study showed that the concentration‐effect relationship of GHB could be characterized in individual rats using aperiodic analysis in the 15.5–30 Hz frequency band.

Purpose. The effect-plasma concentration relationship of etomidate was studied in the rat using electroencephalographic changes as a pharmacodynamic parameter. Methods. Etomidate was infused (50 mg/kg/h) in chronically instrumented rats (n = 6) until isoelectric periods of 5 s or longer were observed in the electroencephalogram (EEG). The EEG was continuously recorded during the experiment and frequent arterial blood samples were taken for determination of etomidate plasma concentrations. The changes observed in the raw EEG signal were quantified using aperiodic analysis in the 2.5−7.5 Hz frequency band. The return of the righting reflex was used as another parameter of anesthesia. Results. A mean dose of 8.58 ± 0.41 mg/kg needed to be infused to reach the end point of 5 s isoelectric EEG. The plasma concentration time profiles were most adequately fitted using a three-exponential model. Systemic clearance, volume of distribution at steady-state and elimination half-life averaged 93 ± 6 ml/min/kg, 4.03 ± 0.24 l/kg and 59.4 ± 10.7 min respectively. The EEG effect-plasma concentration relationship was biphasic exhibiting profound hysteresis. Semi-parametric minimization of this hysteresis revealed an equilibration half-life of 2.65 ± 0.15 min, and the biphasic effect-concentration relationship was characterized nonparametrically by descriptors. The effect-site concentration at the return of the righting reflex was 0.44 ± 0.03 μg/ml. Conclusions. The results of the present study show that the concentration-effect relationship of etomidate can be characterized in individual rats using aperiodic analysis in the 2.5−7.5 Hz frequency band of the EEG. This characterization can be very useful for studying the influence of diseases on the pharmacodynamics of etomidate in vivo.

Benzodiazepines belong to the most widely prescribed group of drugs and are involved in a large proportion of the acute poisonings seen in emergency departments. The aim of the study was to examine whether a relationship exists between the number of poisonings with different types of benzodiazepines and the number of prescriptions for these benzodiazepines. A significant correlation was found between the type of benzodiazepine in cases of acute poisoning seen in the emergency department and (1) the benzodiazepines used as apparent from a sample of the population of the province of East Flanders (Spearman r=0.70, P=0.002), (2) benzodiazepine prescriptions made during a period of 7 weeks by 131 general practitioners (r=0.66, P=0.039, (3) the number of packages of the different benzodiazepines sold in Belgium (r=0.69, P=0.001) and (4) the number of packages sold in Belgium (expressed in DDD; r=0.58, P=0.047). This correlation was found despite the differences in age and geographic characteristics of the populations we studied. We observed more poisonings with diazepam, flunitrazepam and lormetazepam than would be expected from the data on their use in the population. The reason is unclear but the faster onset of action of the benzodiazepines may have led to more frequent hospitalization. Copyright © 1998 John Wiley & Sons, Ltd.

Benzodiazepines belong to the most widely prescribed group of drugs and are involved in a large proportion of the acute poisonings seen in emergency departments. The aim of the study was to examine whether a relationship exists between the number of poisonings with different types of benzodiazepines and the number of prescriptions for these benzodiazepines. A significant correlation was found between the type of benzodiazepine in cases of acute poisoning seen in the emergency department and (1) the benzodiazepines used as apparent from a sample of the population of the province of East Flanders (Spearman r=0.70, P=0.002), (2) benzodiazepine prescriptions made during a period of 7 weeks by 131 general practitioners (r=0.66, P=0.039, (3) the number of packages of the different benzodiazepines sold in Belgium (r=0.69, P=0.001) and (4) the number of packages sold in Belgium (expressed in DDD; r=0.58, P=0.047). This correlation was found despite the differences in age and geographic characteristics of the populations we studied. We observed more poisonings with diazepam, flunitrazepam and lormetazepam than would be expected from the data on their use in the population. The reason is unclear but the faster onset of action of the benzodiazepines may have led to more frequent hospitalization. Copyright © 1998 John Wiley & Sons, Ltd.

The Glasgow coma score (GCS) during days 1-6 after cardiac arrest was used to predict neurological outcome in 360 resuscitated victims of out-of-hospital cardiac arrest. A predictive rule based on the best GCS of 216 patients resuscitated in 1983-84 (prediction group) was constructed, and its predictive power was tested on 133 patients treated in 1985 (test group). Neurological outcome was correctly predicted 2 days after cardiac arrest in 80% of the prediction group, with a best GCS of 10 or above and 4 or below as cutoff points. For patients with a best GCS of 5-9, prediction of outcome was possible 6 days after cardiac arrest, with a best GCS of 8 during the first 6 days as the single cutoff point. The rule was then validated in the test group: the sensitivity was 96%; the specificity 86%; the negative predictive value 97%; and the positive predictive value 77%. These data suggest that this simple GCS-based rule can be helpful in predicting outcome in patients resuscitated after out-of-hospital cardiac arrest, but confirmation of these data is required in a prospective study in a larger number of patients.

Although poisoning with calcium channel blocking agents is frequent, to our knowledge no cases involving amlodipine have been published. We describe here a case of amlodipine intoxication, in which protracted hypotension did not respond to vasopressor therapy alone. After the addition continuous clacium chloride and glucagon infusion, blood pressure was restored and vasopressor therapy could be tapered off substantially. When calcium and glucagon were interrupted because of sever hypercalcemia and hyperglaycemia, the patient developed irreversible hypotension and died. Either glucagon or calcium or both, and to some extent vasopressors, seem to have constituted effective treatment of hypotension in this case.

AbstractCase Report: Propafenone is a class Ic antiarrhythmic agent metabolized into two major metabolites, 5-hydroxypropafenone and N-depropylpropafenone. The potency of 5-hydroxypropafenone to block fast sodium channels is comparable to that of its parent. We report the positive correlation between plasma concentrations and electrocardiographic changes in a patient with severe oral self-poisoning. Serial ECG changes were measured and plasma concentrations were determined by high-performance liquid chromatography. The initial plasma concentrations of propafenone were in the toxic range and correlated with the widening of the QRS-compIex. The slow decline in concentration during this first phase might relate to saturation of the isoenzyme CYP2D6. The half-life of propafenone, calculated from the second phase, was approximately 3 hours, defining the patient as a fast metabolizer. The initial concentrations of the metabolite N-depropylpropafenone were surprisingly higher than those of 5-hydroxypropafenone which may also be due to saturation of CYP2D6.

BackgroundData are scarce about the possible role for the general practitioner (GP) in patients with decreased consciousness (DC) or coma. We wanted to investigate how often a GP is confronted with DC or coma during out-of-hours service in an urban region and to compare the patients presented to primary care to those who were immediately treated by the emergency medical services (EMS).