Proper Understanding and Application of Gastric Lavage

Gastric lavage is one of gastrointestinal decontamination methods which have been controversial in the clinical toxicology field for a long time. Expert groups of American and European clinical toxicologists have published the position papers regarding gastric lavage three times since 1997. They recommended that gastric lavage should not be used as a routine procedure in the management of acute intoxication, because they thought that there is no certain evidence of improving clinical outcome by its use. However, the studies they reviewed were not well-controlled randomized trials, which cannot be conducted in the clinical toxicology field due to variability of patients and ethical problems. Therefore, the results from these studies should be interpreted with caution. They also insisted that gastric lavage can be undertaken within 60 minutes of ingestion. The limitation of one hour after ingestion is too arbitrary and may cause a lot of misunderstanding. Formation of pharmacobezoar or gastric hypomotility after ingestion may significantly delay the gastric emptying time so that gastric lavage can be useful even after several hours or more in case of highly toxic substances or severe intoxication. Furthermore, as there are a number of serious intoxication by toxic pesticides with large amount in suicidal attempts in Korea, it seems that gastric lavage may be used more frequently in Korea than in Western countries. When deciding whether or not to use gastric lavage, all the indications, contraindications, and possible adverse effects should be taken into account on the basis of risk-benefit analysis. If the procedure is decided to be done, it should only be performed by well-trained experts.

Need for stocking of emergency antidotes

No abstract available.

Antidote for organophosphate insecticide poisoning: atropine and pralidoxime

Acute organophosphate (OP) poisoning produces cholinergic symptoms resulting from the inhibition of cholinesterase, and the overstimulation of muscarinic and nicotinic receptors in the synapses. The dominant clinical features of acute cholinergic toxicity include bradycardia, miosis, lacrimation, salivation, bronchorrhea, and bronchospasm. All symptomatic patients should receive therapy with oxygen, atropine, and pralidoxime. Atropine works as a physiologic antidote by competitively occupying muscarinic receptor sites, reducing the effects of excessive acetylcholine. Atropine should be immediately administered, and the dose can be titrated according to the severity of OP poisoning. A large dose may be necessary to overcome the excessive cholinergic state in case of severe poisoning. Pralidoxime is a biochemical antidote that reactivates acetylcholinesterase by removing OP from it. It is effective in treating both muscarinic and nicotinic symptoms. After some period of time, the acetylcholinesterase-OP compound undergoes a conformational change, known as aging, which renders the enzyme irreversibly resistant to reactivation by a pralidoxime. There has been a great deal of controversy over the effectiveness of pralidoxime in acute OP poisoning. However, it may be beneficial to administer pralidoxime for a sufficient period in case of severe poisoning with a large quantity of OP, which is common in Korea.

The Clinical Feature and Prognostic Factor of Glyphosate Intoxication Patients

PURPOSE: Glyphosate is widely used and its toxic exposures are not rare. Occasionally, glyphosate intoxication can lead to death. The aim of this study is to analyze clinical findings and fatality in glyphosate intoxication. METHODS: Clinical data on acute glyphosate intoxication were prospectively collected at 28 hospitals nationwide between August 2005 and July 2006. The patients' clinical symptoms and characteristics of fatalities were investigated and statistical analysis was performed. RESULTS: Among 105 patients who were finally included, gastrointestinal symptoms(59%) were the most common. A significant difference in the amount ingested was observed between patients with higher systolic blood pressure and those with systolic blood pressure less than or equal to 80 mmHg (p<0.001). The more the patients ingested, the more aggravated their mental status became (p=0.004). Seven patients(6.7%) died, and all of them had ingested greater than or equal to 200 ml. Patients who died had ingested greater amounts than the survivors (p<0.001), and their mental status was worse (p<0.001), and systolic blood pressure was lower (p<0.001). According to the result of logistic regression analysis, relative risk was 24.1-fold higher in the 'poor' mental status group compared with 'good'. CONCLUSION: Patients who ingested large amounts of glyphosate showed poor mental status and lower blood pressure. Statistical difference in amount ingested, mental status, and systolic blood pressure was observed between survivors and patients who died. Ingested amounts and mental status were the most important factor of the prognosis of glyphosate intoxication.

Activities and Significance of Clinical Pharmacology in Korea

Over the last two decades, Korean Society of Clinical Pharmacology has performed a pivotal role to have the concept of clinical pharmacology take root in Korea through various academic activities. Clinical pharmacology is not only a research discipline, but also a clinical specialty which aims to provide support for physicians and patients about rational use of drugs. Although it is difficult for any one individual to cover wide range of clinical pharmacology activities, the integrative aspects of the discipline are very important to the development and use of drugs. Recently the world has been faced with serious economic crises and pharmaceutical companies have been shrunken in their research and development, so that clinical pharmacology also has been internationally affected. However, clinical pharmacology has been rapidly grown up in Korea despite the negatively given condition. At this time it is important for physicians in this field to understand the background of our clinical pharmacology in order to complement and develop our current situation for the future. In this review the academic achievement in clinical pharmacology in Korea is valued through looking back our activities for the past twenty years.

Radiological Accident and Acute Radiation Syndrome

In mass casualty situation due to radiological accidents, it is important to start aggressive management with rapid triage decisions. External contamination needs immediate decontamination and internal contamination should be treated with special expertise and equipment to prevent the rapid uptake of radionuclides by target organs. Acute radiation syndrome shows a sequence of events that varies with the severity of the exposure. More severe exposures generally lead to more rapid onset of symptoms and severe clinical findings. After the massive exposure, various systems of the body reflect their severe damages that can lead to death within hours or up to several months. The disease progression has classically been divided into four stages: prodromal, latent, manifest illness, and recovery or death. Three characteristic clusters of symptoms including the hematopoietic syndrome, the gastrointestinal syndrome and the cerebrovascular syndrome are all associated with the acute radiation syndrome. The standard medical management of the patients with a potentially survivable radiation exposure includes good medical, surgical and supportive measures. Specific treatment with cytokines and bone marrow transplantation should be considered. The management of internal contamination is much the same as the treatment of poisoning. The standard decontamination should be applied to reduce uptake, and the chelating agents can be administered to enhance the clearance of radioisotopes. Radioactive iodine (131I) as one of the nuclear fission products can increase the incidence of thyroid cancer in children. Potential benefit of potassium iodide prophylaxis is greater especially in neonates, infants and small children.

Clinical Characteristics of Acute Zolpidem Intoxication

PURPOSE: The hypnotic effect of zolpidem is comparable to benzodiazepines, but has less abuse and addiction potential than benzodiazepines, so is one of the most commonly prescribed hypnotics. The frequency of acute zolpidem overdose has increased, but clinical analysis and severity predictors are not known in Korea. METHODS: A retrospective evaluation of histories, clinical courses, and laboratory findings of each patient treated from June, 2000, to May, 2006, in a university hospital for acute zolpidem intoxication. RESULTS: We evaluated 30 patients, including 16 co-intoxication cases. Twenty-five patients presented mental alterations but became alert within 2 days. All patients recovered completely. The median zolpidem concentration was 0.9 mg/L (range: 0.2~7.4 mg/L). There was a weak correlation between the amount ingested and zolpidem concentration (r=0.25). None of them presented severe laboratory abnormalities, and these abnormalities did not relate to zolpidem concentration. CONCLUSION: The clinical progress of acute zolpidem intoxication is mild. We could not predict zolpidem concentration or clinical severity from the amount ingested and could not predict the clinical course from laboratory findings in the emergency department.

Clinical Characteristics of Acute Dichlorvos Poisoning in Korea

Purpose: Dichlorvos has been in widespread use as an organophosphate (OP) insecticide compound. The purpose of this study was to access the epidemiology and clinical features of dichlorvos in Korea. Methods: This was a 38 multi-center prospective study of dichlorvos poisoning using surveys, a structural reporting system and review of hospital records from August 2005 to July 2006. A total of 54 patients with acute dichlorvos poisoning on a national basis were enrolled. We analyzed the epidemiologic characteristics and clinical manifestations of dichlorvos poisoning. In addition, the clinical features of dichlorvos poisoning were compared with others OP compounds. Results: During the study period, compounds involving pure OP poisoning were dichlorvos (22.7%), methidathion (8.4%), and phosphamidon (6.7%). In acute dichlorvos poisoning, all ingestion routes were oral. Intentional poisoning involved 74.1% of cases. The common initial complaints involved gastrointestinal (64.8%), systemic (61.1%), central or peripheral nervous system (53.7%), and respiratory symptoms (50.0%). The median arrival time to hospital after dichlorvos poisoning was 2.6 hours and mean hospitalization duration was 7.1 days. 2-PAM was administered in 35 patients in mean doses of 6.3 g/day intravenously. Atropine was administered in 30 patients with a mean dose of 62.8 mg/day (maximal 240 mg/day). Overall mortality rate for dichlorvos poisonings were 14.8% (8/54). Immediate causes for death included sudden cardiac arrest or ventricular dysrhythmias (50%), multi-organ failure (25%), acute renal failure (12.5%), and unknown causes (12.5%). Conclusion: When compared to previous reports, dichlorvos poisoning displayed relatively moderate severity. The presence of a lower GCS score, altered mental status, serious dysrhythmias, systemic shock, acute renal failure, and respiratory complications upon presentation were associated with a more serious and fatal poisoning.

Clinical Implication of Acetylcholinesterase in Acute Organophosphate Poisoning

Purpose: Acute organophosphate (OP) poisoning may be monitored by measuring the acetylcholinesterase (AChE). It is important to assess severity and establish prognostic tests in the early stage of OP poisoning. The aim of this study was to look at the relationship between various clinical aspects of the OP poisoning, prognostic indicators of OP poisoning including Simplified Acute Physiology Score (SAPS) 3, and the associated changes in AChE levels. Methods: Clinical data and initial AChE levels from thirty-seven patients with OP poisoning were prospectively reviewed from 12 teaching hospitals in South Korea from August 2005 to July 2006. Clinical manifestations at the time of arrival such as miosis, respiratory abnormality, salivation, urinary incontinence, GCS score, AVPU scale, need for intubation, and mechanical ventilation requirements were recorded. SAPS 3 was calculated using clinical data and laboratory results. Results: The median level of AChE was 9.8 (1.3-53.6) U/gHb. There was no significant difference in AChE levels between the groups with and without cholinergic symptoms. The median level of AChE of the patients who required intubation and those who did not were 3.5 U/gHb and it 19.7 U/gHb respectively (Mann-Whitney test; p<0.001). The AChE levels were also significantly different (p=0.007) in patients who needed mechanical ventilation compared to those who did not with AChE levels found to be 3.1 U/gHb and it was 14.8 U/gHb, respectively. Level of consciousness assessed using the AVPU scale was correlated with AChE levels (Kruskal-Wallis test; p=0.013). GCS score were correlated with AChE levels (p=0.007, Spearman's rho = 0.454). In addition, the lower the level of initial AChE, the longer the ICU stay (p=0.029, Spearman's rho=-0.380). SAPS 3 was inversely correlated with the initial AChE (p<0.001, Spearman's rho=-0.633). Conclusion: In the acute OP poisoning, low AChE levels appear to help indicate the severity of poisoning. The initial AChE level may be a useful prognostic parameter for acute OP poisoning.

A Case of Amitraz Insecticide Intoxication after Ingestion of Large Amount

Amitraz is used as farm-animal insecticide. Its side effects in humans are related to its pharmacological activity on alpha 2-adrenergic receptors. The case describes a previously healthy 46-year-old woman who intentionally ingested approximately 250mL of liquid amitraz. She presented with vomiting, altered mental status, miosis, dry mouth, hypopnea, metabolic and respiratory acidosis, hypotension, hypothermia, polyuria, metabolic acidosis, elevated serum aminotransferase and abdominal distension. Supportive treatments including mechanical ventilation, hydration, dopamine infusion, bicarbonate infusion and gastric decompression resulted in improvement. By hospital day 3, she recovered with resolution of abdominal distension. It is paramount to recognize amitraz poisoning when apesticide-intoxicated patient presets with signs and symptoms consistent with organophosphate intoxicated patients but with greater alpha 2-adrenergic related symptoms such as decreased bowel motility and xerostomia.

A fatal case of acute arsenic poisoning / 대한내과학회지

Arsenic trioxide is the most prevalent natural inorganic form of arsenic, which is a widely used heavy metal and is ubiquitously distributed in the environment. A 71-year-old man ingested about 10 g of arsenic trioxide powder in an attempted suicide. He developed severe vomiting, watery diarrhea and abdominal pain, and he presented to the emergency room 15 hours after the ingestion. On admission he was slightly drowsy, but shocked. He showed metabolic acidosis, acute renal failure and abnormal electrocardiogram suspecting myocardial infarction. The chest and abdominal X-rays revealed radiopaque materials in the stomach and small bowel. The stomach was irrigated via a nasogastric tube and activated charcoal was given to bind unabsorbed arsenic. The whole bowel irrigation was tried to remove the remained arsenic in the gastrointestinal tract and BAL (British anti-lewisite) was repeatedly administrated. Despite of intensive supporting management with supplemental oxygen, aggressive volume expansion, correction of metabolic disturbances and administration of cardiotonic agents, he developed progressive hypotension and died 42 hours after the ingestion. Random urine arsenic concentration, which was collected at the time of admission, but confirmed after death, was 3,564 microgram/L.

A Retrospective Review of Patients Who Ingested Liquid Household Bleach Containing Sodium Hypochlorite

PURPOSE: Bleaching agents containing sodium hypochlorite are widely used at home to bleach laundry and to disinfect hard surfaces. A retrospective study, with a literature review, was conducted to focus attention on the clinical outcome after accidental or intentional ingestion of sodium hypochlorite. METHODS: The medical records of 67 patients presented to the Inha University emergency department for sodium hypochlorite ingestion between June 1996 and July 2003 were retrospectively examined. RESULTS: The Mean volume of the bleach in the 56 patients who ingested the bleach in a suicide attempt was significantly larger than that of the 11 patients with accidental ingestion (P=0.001). Nausea and vomiting was present in 79% of the patients. The volume of ingestion in patients with vomiting was significantly larger than that in patients without vomiting (P=0.001). Patients with epigastric pain ingested larger volumes of bleach compared to patients without the pain (P=0.01). Endoscopic examinations were performed in seven patient, and normal findings were seen in three patients. Grade 1 caustic injury was observed in two patients, and Grade 2 injuries in the rest. CONCLUSION: The solution of the sodium hypochlorite may cause mild symptoms and seems to be safe after ingestion. However, careful evaluation with endoscopy and hospital admission should be considered if there are symptoms or signs suggesting caustic injury of the esophagus and/or stomach or if the ingested volume is large.

Management of acute intoxication / 대한내과학회지

No abstract available.

Prognostic factors in acute paraquat intoxication / 대한내과학회지

No abstract available.

Polymorphism of CYP2D6*10B of Patients with Schizophrenia in Korean Population / 신경정신의학

OBJECTIVES: This study was done to compare the proportion of the CYP2D6*10 allele between previously reported data of normal Korean subjects and schizophrenic patients. And we investigated the relationship between the CYP2D6*10 allele and the clinical variables such as age of onset, duration of illness and psychopathology. METHODS: Total 82 DSM-IV Korean schizophrenic patients in monotherapy with risperidone participated in this study. The CYP2D6*10 allele which contains C188T mutation in exon 1 was identified by allele specific PCR amplification. We investigated the clinical variables such as age of onset and duration of illness through chart review. The baseline psychopathology with brief psychiatric rating scale (BPRS) before blood collection were done in clinically stable patients. RESULTS: Seventeen (20.7%) out of 82 patients were homozygous for CYP2D6*1, 22 (26.8%) for *10, while the remaining 43 patients (52.4%) were heterozygous for these alleles. These distributions were very similar with previously reported data of Korean normal subjects. There was no significant relationship between the CYP2D6*10 allele and the clinical variables such as age of onset, duration of illness and psychopathology. CONCLUSION: In Korean schizophrenic patients, there was no significant difference in CYP2D6*10 allele compared to normal Korean subjects.

Assessment of flavin-containing monooxygenase (FMO) activity by determining urinary ratio of theobromine and caffeine in a Korean population after drinking a cup of coffee

To examine individual variation in drug metabolism catalyzed by flavin-containing monooxygenase (FMO), 179 Korean volunteers' urinary molar concentration ratio of theobromine (TB) and caffeine (CA) was determined. Their urine was collected for 1 hr (between 4 and 5 hrs) after they drank a cup of coffee containing 115 mg CA and analyzed by an HPLC system. The lowest TB/CA ratio obtained was 0.40, the highest ratio was 15.17 (38-fold difference), and the median ratio for all subjects was 1.87. The mean was 2.66 with 2.36 S.D.. In 134 nonsmokers, the mean ratio was 2.35 +/- 1.93, that of 51 males was 2.30 +/- 2.26 and 83 females was 2.37 +/- 1.85, respectively. There was no significant gender difference in the obtained TB/CA ratio (Mann-Whitney test; p=0.518). There were no smokers among the 83 female volunteers. In the remaining 96 male subjects, the ratio obtained in 51 nonsmokers was 2.30 +/- 2.06 and that of 45 smokers was 3.62 +/- 3.19. This indicated that the TB/CA ratio was increased significantly in smokers (p=0.007). However, when the TB/CA ratios (FMO activity) obtained in all 179 Korean volunteers are compared with the urinary concentration ratios of paraxanthine (PX) plus 1,7-dimethylurate (17U) to CA (CYP1A2 activity), there was a weak but significant correlation (Pearson's correlation coefficient test; r2=0.28, p<0.0001). This indicates that, although the urinary TB/CA ratio mostly represents FMO activity, minor contribution by CYP1A2 activity cannot be ignored. In conclusion, the FMO activity measured by taking the urinary TB/CA ratio from normal healthy Korean volunteers shows marked individual variations without significant gender differences and the increased TB/CA ratio observed in cigarette smokers may have been caused by the increased CYP1A2 activity.

The Effects of Urokinase Instillation Therapy via Percutaneous Transthoracic Catheter Drainage in Loculated Tuberculous Pleural Effusion: A randomized prospective study / 결핵

BACKGROUND: Tuberculous pleural effusion responds well to the anti-tuberculosis agents in general, so no further aggressive therapeutic managements to drain the tuberculous effusion is necessary except in case of diagnostic thoracentesis. But in clinical practice, we often see some patients who later decortication need due to dyspnea caused by pleural thickening despite the completion of anti-tuberculosis therapy in the patients with tuberculous effusion. Especially, the patients with loculated tuberculous effusion might have increased chance of pleural thickening after treatment. The purpose of this study was that intrapleural urokinase instillation could reduce the pleural thickining in the treatment of loculated tuberculous pleural effusion. METHODS: Thirty-seven patients initially diagnosed as having loculated tuberculous pleural effusion were randomly assigned to receive either the combined treatment of urokinase instillation and anti-tuberculosis agents(UK group) and anti-tuberculosis agents(Non-UK group) alone. The 16 patients in UK group received a single radiographically guided pig-tail catheter ranging in size from 10 to 12 French. 100,000 units of urokinase was dissolved in 150 ml of normal saline and instilled into the pleural cavity via pig-tail catheter every day, also this group was treated with anti-tuberculosis agents. While the 21 patients in Non-UK group were teated with anti-tuberculosis agents only except diagnostic thoracentesis. Then we evaluated the residual pleural thickening after treatment for their loculated tuberculous pleural effusion between the two groups. Also the duration of symptoms and the pleural fluid biochemistry like WBC counts, pH, lactic dehydrogenase (LDH), glucose, proteins, and adenosine deaminase (ADA) were compared. RESULTS: 1) The residual pleural thickening (RPT) (5.08 +/- 6.77 mm) of UK group was significantly lower than that (20.32 +/- 26.37 mm) of Non-UK group (Por=10 mm(5.23 +/- 3.89 wks) was significantly longer than the patients with RPT or=10 mm and the patients with RPT <10 mm. CONCLUSION: The treatment of loculated tuberculous pleural effusion with the urokinase instillation via percutaneous transthoraic catheter was effective to reduce the pleural thickening.

A Case of Broncholithiasis caused by Aspergillus / 결핵

Broncholith is a calcified lymph node which partially or completely erodes into the bronchial lumen and broncholithiasis is a relatively rare condition which related to late tissue response to healing granulomatous pulmonary infections, most commonly histoplasmosis or tuberculosis. The prominent symptoms of broncholithiasis are coughing followed by hemoptysis and symptoms related to bronchial obstruction. The complications include bronchoesophageal fistula and aortotracheal fistula. We report one case of broncholithiasis caused by Aspergillus. The case was a 53 year-old house wife whose chief complaints were recurrent fever, chill and malaise. The chest film revealed an ovoid hazziness on the right middle lobe and chest CT scan showed consolidation of lateral segment of right middle lobe with calcified small low attenuated lesion in right middle lobe bronchus. Aspergillosis confirmed by pathology after bronchoscopic removal of impacted Aspergillus containing muddy plug from lateral segmental branch of right middle lobe bronchus.

Thiobenzamide S-oxidation in perfused rat liver: Ex vivo determination of hepatic flavin-containing monooxygenase activity

An ex vivo assay determining the flavin-containing monooxygenase (FMO) activity in perfused rat liver has been developed by assessing the rate of thiobenzamide S-oxide (TBSO) formation from the infused thiobenzamide (TB). The hepatotoxicity by TB or TBSO was not a critical factor for maintaining the FMO activity for up to 50 min. The FMO activity expressed in nmoles TBSO produced/g liver/min was the same for the recycling and non-recycling perfusion. This implies that reduction of the oxidized TBSO back to the parent compound (TB) is negligible. Hydrolysis of the collected perfusates with either beta-glucuronidase or arylsulfatase did not increase the TBSO level and thus, TBSO does not appear to undergo conjugation either to glucuronide or sulfate esters. Thus, measuring the rate of TB S-oxidation in the isolated perfused liver with 1 mM TB for 50 min provides a useful tool for evaluation of the hepatic FMO activity in the absence of hepatic necrosis and without the interferences caused by further conjugation or back reduction of the TBSO to the parent TB.

Inhibitory Drug Interaction

No abstract available.