Poison Center, MacKay Memorial Hospital

2023年12月3日星期日

河魨毒素中毒, Tetradotoxin, TTX

Substance

Tetrodotoxin, TTX

河魨毒素中毒主要發生於魨形目魚類. 雖然這種魚的分佈不受地理位置的限制，但它在日本、加利福尼亞、非洲、南美和澳大利亞的食用頻率最高。在佛羅里達和新澤西，以及歐洲、地中海和孟加拉，也發生了90起相關病例。

魨形目約有100種淡水或鹹水魚.河魨毒素也會在藍圈章魚[1]，腹足綱生物(Gastropods) 甚至在一起鱟魚卵[2]中毒死亡個案中被驗出 .在美國的一些蠑螈[3]皮膚亦驗出此毒素，這些蠑螈通常具有鮮豔顏色及粗躁表皮 (4)。

河魨毒素在一般的加熱環境中能維持穩定，水溶性的非蛋白質分子, 分子結構在酸性環境中且加熱至100°C (華氏212度)才會開始不穩定。河豚毒素屬於神經毒素，強度與痲痺性貝毒相當，約為氰化鈉之1000倍以上(5)。

大部分毒素分布在河豚的皮膚、肝臟、卵巢、腸子、及部分魚種的肌肉組織。卵巢通常是濃度最高器官，尤其在產卵季節。

河魨毒素的檢測，過去主要靠生物毒性檢驗法(mouse bioassay)，目前則是使用螢光光譜分析法(fluorescence spectrometry) ，或是將疑似中毒患者尿液結合免疫親和性層析(immunoaffinity chromatography) 及螢光高效能液相層析法(fluorometric HPLC) 來偵測(4)。

河魨毒素由海洋細菌產生，並且可能在食用這些細菌的食物鏈上層動物中積聚。這種毒素的積聚是單純的演化適應，用以清除有毒物質，還是具有演化上的保護優勢，目前尚不清楚(4)。

Common name

河魨毒素

Toxin found in Pufferfishes, globe fish, Balloon fish, blowfish, toadfish蟾魚, 豹蟾魚. [4, 6, 7, 8]

Toxin in Blue-Ringed Octopus 藍圈章魚 [1, 9, 10 ]

Toxin in Taricha newt (蠑螈) [3]

Involving system

N-M junction: 神經毒性的病理機轉是由抑制鈉通道和阻斷神經肌肉傳遞所產生。其分子中含有一個適應於鈉通道外口的胍基組，它將鈉通道從神經元的外表面阻擋。這導致鈉通道的外部「塞住」，儘管閘控機制仍然保持功能，但鈉離子無法進出通道，造成節前神經元中斷產生神經傳導物質，神經傳導中斷(1, 6, and 9)。

Respiratory and CV system: 嚴重時可能抑制呼吸系統功能及造成低血壓(1, 4, 5, 6)。

Presentation河豚毒素中毒的臨床表現

GI system: nausea, vomiting, and abdominal pain. [1, 5, 6]

Neurologic and CV:河豚毒素中毒的典型症狀包括嘴舌麻木、頭暈、手部麻木、四肢無力、心臟不適(2)。這些症狀通常在食用受污染的河豚後數分鐘至數小時內出現，通常是10-45分鐘產生(2)。在Goldfrank's Toxicologic Emergencies中提到嚴重的症狀可能導致複視、視覺模糊、說話困難和呼吸困難，瞳孔擴大、抽搐、血壓下降、肌肉鬆弛、muscle weakness [8]橫隔膜運動停止這些都與河豚毒素對神經系統的影響相關。

Risk to Respiratory failure: 隨著中毒情況的惡化，患者可能會出現進一步的神經肌肉弱化，導致全身麻痺，最終可能 (4 to 24 hours ascending paralysis) 進展至呼吸衰竭死亡(1,2, 4, 6, and 7)。

Antidote治療與解毒策略

目前尚無特效解毒劑可用於河豚毒素中毒。

- Supportive 治療主要針對支持性療法和症狀管理，包括維持呼吸和心血管功能。重點在於迅速識別中毒徵狀並進行及時的醫療干預。[5]

- Intubation with Mechanical Ventilator support在某些情況下，可能需要機械通氣來支持呼吸功能。此外，維持適當的血液循環和血壓也是關鍵(5 , 10)。

- Neostigmine, no strong evidence-based recommendation.[4]

- ACLS [6]

Disposition病例處理與預後

- Mortality rate is around 50 to 61%. [4, 5]

河豚毒素中毒患者的處理需要密切監測和長期觀察，特別是在嚴重中毒的情況下。監測重點包括呼吸、心血管和神經系統功能。

- 預後取決於中毒的嚴重程度以及治療的及時性。

- 多數患者在適當的支持性治療下能夠完全康復，

- 但在嚴重中毒案例中，病情可能迅速惡化，導致呼吸衰竭甚至死亡(5)。

References:

[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6563023/

[2] https://pubmed.ncbi.nlm.nih.gov/36208552/

[3] https://pubmed.ncbi.nlm.nih.gov/34919907/

[4]. Laura JF, Michael GT. Food Poisoning. In: Nelson LS, editor. Goldfrank’s Toxicologic Emergencies. New York Mcgraw-Hill Medical; 2019.11^th ed. P.576, 596

[5].行政院衛生署食品藥物管理局. 河豚毒素 [Internet]. 行政院衛生署食品藥物管理局. 2010 [cited 2023 Dec 3]. Available from: https://www.fda.gov.tw/TC/sitecontent.aspx?sid=1949

[6] https://omjournal.org/articleDetails.aspx?coType=1&aId=3409

[7] https://pubmed.ncbi.nlm.nih.gov/24368916/

[8] https://pubmed.ncbi.nlm.nih.gov/17533966/

[9] https://pubmed.ncbi.nlm.nih.gov/33913398/

[10] https://pubmed.ncbi.nlm.nih.gov/19238736/

Edited by Hsiu-Wu Yang, Nai-Hui Lin, and Yu-Jang Su

Dec 3, 2023.

2023年11月8日星期三

Toluene Poisoning / Intoxication

Substance

Toluene

Common name or Trade name

C₆H₅CH₃

C₇H₈

甲苯: 汽車排放的廢氣，油漆、油漆稀釋劑、指甲油、噴漆及黏著劑 possibly contains甲苯

Route: inhalation of fumes, ingestion, or transdermal absorption [1, 2]

Exposure: 77% were male and mean age was 23.5 years [3]

Involving system

CNS: marked atrophy of the lower cervical spinal cord, thoracic spinal cord, and conus medullaris. [4]

Reversible symmetrical white matter changes [ 5]

Lung: aspiration pneumonitis. [2]

CV system: potential arrhythmogenic effect of endogenous catecholamines, occasionally resulting in fatality.[6]

Kidney: Renal glomerular injury (proteinuria)戊 renal tubular acidosis[2]

Muscle: Rhabdomyolysis occurred in 80% of patients, probably due to hypokalemia and hypophosphatemia [3, 7]

Cardiopulmonary failure [1]

The cause of death was in all cases due to cardiac rhythm abnormalities. [7]

Presentation

Chronic: mild cognitive impairment, hearing impairment, dysarthria, marked hyperreflexia of the limbs, spastic paraplegia, slight impairment of deep sensation, and urinary disturbance. 4 stimulus-sensitive spinal myoclonus [8]

Acute: Severe hypokalemia and acidosis.

. Biliary tract injury (alkaline phosphatase and gamma-glutamyl transpeptidase elevations) disproportional to hepatocellular injury is common.

Altered mental status, severe acidosis, hypokalemia and acute oliguric renal failure. [3, 7]

Symptomatic hypokalemia [2]

Adrenal insufficiency secondary to bilateral adrenal hemorrhage [9]

Antidote and Treatment

No antidote

Standardly supportive treatment

Disposition

If asymptomatic, observe 6 hours, and discharge when the CXR is unremarkable.[2]

Poor in patients who have altered mental status, renal failure, severe acidemia and female gender, and patients with these characteristics should be considered to be treated in an intensive care unit. [7]

References

[1]https://pubmed.ncbi.nlm.nih.gov/24164003/

[2]. Goldfrank’s toxicologic emergencies. 11^th ed. P. 1415~1417

[3].https://pubmed.ncbi.nlm.nih.gov/22642292/

[4]https://pubmed.ncbi.nlm.nih.gov/32238742/

[5].https://pubmed.ncbi.nlm.nih.gov/25117062/

[6]. https://pubmed.ncbi.nlm.nih.gov/9140324/

[7].https://pubmed.ncbi.nlm.nih.gov/26282250/

[8]https://pubmed.ncbi.nlm.nih.gov/10845207/

[9]https://pubmed.ncbi.nlm.nih.gov/9711204/

Edited by Yu-Jang Su Nov 8, 2023

2023年10月19日星期四

Poly-ether siloxane Mis-swallowing

速展王 (離子型黏著劑)

SUBSTANCE: Polyetheretherketone, PEEK; poly-ether siloxane.

cyclic siloxanes D4 (tetramethylcyclotetrasiloxane) and

D5 (decamethylcyclopentasiloxane) and The short-linear HMDS (hexamethyldisiloxane)

General information: Seek medical advice.

If breathing is irregular or stopped, administer artificial respiration.

Inhalation: Move to fresh air.

Skin Contact: Wash off immediately with soap and plenty of water.

Wash off immediately with plenty of water for at least 15 minutes.

Eye contact: Rinse immediately with plenty of water for at least 15 minutes. Rinse

immediately with plenty of water, also under the eyelids, for at least

15 minutes. Remove contact lenses.

Ingestion: Prevent aspiration of vomit. Turn victim's head to the side.

Never give anything by mouth to an unconscious person. If swallowed, seek

medical advice immediately and show this container or label.

Personal Protection for First aid Responders: Use personal protective equipment., Wear self-contained breathing apparatus for firefighting if necessary.

Most important symptoms/effects, acute and delayed

Symptoms: Up to now no symptoms are known. Hazards: No data available.

Indication of immediate medical attention and special treatment needed

Treatment: Treat symptomatically

Toxicokinetic: D4 is eliminated via the lungs and metabolised D4 via urine and faeces

Acute toxicity

In general the acute toxicity of siloxanes is considered low. LD50 following oral

administration of D4 in rats is reported to be more than 4,500 mg/kg and

more that 5,000 mg/kg for HMDS. LC50 in rats exposed to D4 was >12.17

mg/l and >48 mg/l when exposed to HMDS (European Commission 2000).

LD50 following dermal application of D4 was >2400 mg/kg bw. Several studies with dermal application of HMDS have shown greater LD50 values, but

mortality was observed at 10000 mg/kg bw.

Toxic effects at 10000 mg/kg included gross pathological findings (lung, kidney, bladder, heart), while clinical findings (altered activity, ataxia, gasping and eschar formation) occurred in small numbers of rabbits.

Investigation of subacute oral toxicity in rats administered between 25 and

1600 mg/kg per gavage over two week with five applications per week caused

increased relative liver weights in female animals at 100 mg/kg and male animals at 400 mg/kg. Absolute liver weight was also increased in female rats at

400 mg/kg. Decreased body weight was seen at the highest concentration in

both male and female animals (BAuA 2001).

References:

https://www.palmerholland.com/Assets/User/Documents/Product/49053/8825/MITM11654.pdf

https://www2.mst.dk/udgiv/publications/2005/87-7614-756-8/pdf/87-7614-757-6.pdf

Edited by Yu-Jang Su Oct 19, 2023.

2023年9月24日星期日

Recent Ten Articles Describing Overdose / Poisoning in Seasonality

Year	Country	Major Finding	References
2023 Aug	Taiwan	Intentional drug overdose, IDO occurred most frequently in spring (32.1%), particularly in male patients (28/49 male cases). First-time IDO occurred most frequently in spring (51/133 first-time cases) Repeat IDO occurred most frequently in autumn (20/63 repeat cases). Female conflict with father and/or boyfriend, and personality disorder in patients who overdosed, showed seasonality with a spring peak. Hospital admission rate was highest in winter (10/45 winter cases [22.2%]).	[1]
2023 Jul	China	Female patients accounted for a higher proportion (72.5%), and the incidence of suicide was higher in winter than other seasons. Among the 109 psychiatric patients, 60 patients (55.0%) had a history of major depressive disorder Thirty-seven patients (33.9%) experienced severe physical complications caused by drug overdose, with lung infections being the most common. 2 patients (1.8%) older than 80 failed to survive.	[2]
2023 Aug	UK	The rate peaked in Spring and was 1.07 (95% CI = 1.04-1.09) times higher in April than in October. The rate at New Year was 1.28 (95% CI = 1.17-1.41) times higher than on non-holidays; and this peak was only present for deaths that were not related to opioids. The rate was higher on Saturday than on other weekdays. We did not find evidence that the number of deaths varied by week-of-month.	[3]
2021 Dec	US	Show the spring months have the most consistent increases in overdose deaths and overdose calls for service across years we studied.	[4]
2020 Nov	US	Showed that the number of cases associated with poisoning suicide attempts peaked in the Spring and dipped in the Fall. Regression analysis showed higher numbers of suspected suicide attempts from intentional overdose in spring compared with winter by 1.07 times (p = 0.003), and on Sunday (p < 0.001), Monday (p < 0.001), and Thursday (p = 0.02) compared with Saturday by at least 1.09 times. Lower numbers of cases around Christmas (3 days before and after; 22.0 vs. 32.3 on control dates, p < 0.001).	[5]
2012	Polish	The number of intoxication-related admissions proved to be significantly higher on Monday whereas significantly lower on Saturday. As far as the yearly seasonality is concerned the number of admissions to the Clinic was significantly below the average in February and in the period from August to October while it was significantly above the average in January and March.	[6]
2012 Apr	Iran	A remarkable peak in suicides was observed in May and July, while winter had the highest suicide rate among seasons.	[7]
2005 Jul	Nepal	Seasonal variation in poisoning was observed with more cases in the summer months. Intensive care unit (ICU) service was required in 17% of patients; and almost 25% developed complications. Ninety four percent of admitted patients recovered completely; leaving a mortality rate of 5%.	[8]
1997 Dec	State of Bahrain	A seasonal variation was noted with 46% of the cases occurring in the summer months.	[9]
1992 Apr	Bulgaria	Over the week, the smallest number was on Saturdays. There was a slight seasonal variation, with the highest number in March and the lowest in August.	[10]

References

[1] https://pubmed.ncbi.nlm.nih.gov/37632450/

[2] https://pubmed.ncbi.nlm.nih.gov/37226659/

[3] https://pubmed.ncbi.nlm.nih.gov/36843423/

[4] https://pubmed.ncbi.nlm.nih.gov/35619981/

[5] https://pubmed.ncbi.nlm.nih.gov/32141348/

[6] https://pubmed.ncbi.nlm.nih.gov/23243906/

[7] https://pubmed.ncbi.nlm.nih.gov/22424037/

[8] https://pubmed.ncbi.nlm.nih.gov/16554862/

[9] https://pubmed.ncbi.nlm.nih.gov/9519674/

[10] https://pubmed.ncbi.nlm.nih.gov/1571762/

Edited by Yu-Jang Su Sep 24, 2023

2023年8月19日星期六

Abamectin / emamectin/ Ivermectin Intoxication

Year	Country	Substance / Dose	Treatment / Outcome	Reference
2003	Taiwan	Oral application of ABM (20 mg/kg)	Concomitant epinephrine injection [100 micro-gm/ kg, subcutaneously (s.c.).	1
1999	Taiwan	Eighteen patients with abamectin (Agri-Mek; 2% wt/wt abamectin) exposure and 1 with ivermectin (Ivomec; 1% wt/vol ivermectin) ingestion.	Male: Female =14: 5 37% coma 37% admit to ICU 21% asymptomatic 16% hypotension 5% die of MOF.	2
2022	Taiwan	60 had ingested emamectin pesticides, and 4 had ingested abamectin.	Drowsiness (47%) Shortness of breath (SOB)/dyspnea (33%) Nausea/vomiting (22%). (27%) were intubated. (31%) had severe outcomes. (78%) were admitted 42% required intensive care unit (ICU). 6.3% died GCS score < 13 (OR 68.1, 95% CI 3.8-999) and the presence of SOB/dyspnea (OR 50.2, 95% CI 3.0-849.9) were associated with severe outcomes.	3
2015	People's Republic of China	Ingestion of a large dose of abamectin on purpose	Rapidly recovered consciousness after administration of flumazenil.	4
2004	Taiwan	Proclaim insecticide (Syngenta, Taiwan), consisting of 2.15% w/w emamectin benzoate in 2, 6-bis (1, 1-dimethylethyl)-4-methyl-phenol and 1-hexanol.	Transient gastrointestinal upset with endoscopy-proven gastric erosion and superficial gastritis, mild central nervous system depression, and aspiration pneumonia. Treated successfully with gastric lavage, administration of activated charcoal, and empiric antibiotics.	5
2007	Turkey	Toxic effects of abamectin are usually seen after abamectin oral ingestions.	Altered mental status, respiratory failure, and hypotension.	6
2016	China	acute avermectins poisoning	Nystagmus is rarely reported	7
2014	Iran	3600 mg abamectin orally.	Gastric lavage charcoal was administered. Altered mental status drowsiness, hypotension, tachycardia and dermal erythema. Treated as H1 and H2 blockers and vasoactive agents Altered mental status could be considered as the first sign of abamectin intoxication. Conservative treatment is recommended.	8
2020	People's Republic of China	400 mL of 5% abamectin pesticide.	Serious brain dysfunction and abnormal EEG caused by abamectin poisoning are treatable. Despite poor clinical and EEG findings at the outset, recovery is still possible.	9

1. https://pubmed.ncbi.nlm.nih.gov/12948083/

2. https://pubmed.ncbi.nlm.nih.gov/10381994/

3. https://pubmed.ncbi.nlm.nih.gov/35916769/

4. https://pubmed.ncbi.nlm.nih.gov/26360693/

5. https://pubmed.ncbi.nlm.nih.gov/15462160/

6. https://pubmed.ncbi.nlm.nih.gov/17453886/

7. https://pubmed.ncbi.nlm.nih.gov/24280654/

8. https://pubmed.ncbi.nlm.nih.gov/25948975/

9. https://pubmed.ncbi.nlm.nih.gov/33094704/

Edited by Yu-Jang Su Aug 19, 2023

2023年7月9日星期日

Current Ten Clinical Studies on New Psychoactive Substances in Taiwan

Year	Journal	University, Hospital.	Finding, Conclusion	Reference
2016	Subst Abuse Treat Prev Policy	Kaohsiung Medical University	Controlled NPS items in Taiwan were far less than those in Korea, but the quantity of total NPS seizures, especially with ketamine, was much larger in Taiwan than in Korea.	1
2017	Forensic Sci Int	Kaohsiung Medical University	Japan is the most proactive country in terms of the NPS regulation with 41% of the total number of controlled NPS in Northeast Asia, followed by South Korea (21%), China (28%), Taiwan (10%)	2
2020	J Formos Med Assoc	National Taiwan University Hospital	The most common NPS was ketamine (21.7%), followed by synthetic cathinones (14.8%). Polysubstance use was more common in the NPS group than in the traditional group. Most patients were men (78.3%)	3
2022	Clin Toxicol (Phila) .	Linkou Chang Gung Memorial Hospital	The most frequently detected drug was methamphetamine/amphetamine, followed by synthetic cathinones, ketamine and its two analogs, and opioids. Younger patients and women were more likely to have NPS detected in their urine samples. NPS-positive cases frequently experienced chest pain tachycardia and suicide attempt/non-suicidal self-harm whereas depressed consciousness was less frequent among NPS-positive cases than among other illicit drug-positive cases.	4
2022	J Formos Med Assoc	National Taiwan University College of Medicine	546 (73.7%) men and 195 (26.3%) women were enrolled. Compared to men, women were younger (32.03 ± 10.86 vs. 36.51 ± 10.84 years, p < 0.001) and more likely to use new psychoactive substances (NPS). Men were more likely to have HIV infection, whereas women were more likely to report psychiatric comorbidities. Women were less likely to have aggressive behaviors. The likelihood of rhabdomyolysis and intensive care unit admission was higher in men (p < 0.001).	5
2022	Clin Toxicol (Phila)	National Taiwan University College of Medicine	Tachycardia, hyperthermia, and rhabdomyolysis were more common among cathinone users than among meth/amphetamine users presented to EDs.	6
2022	J Formos Med Assoc	Taipei City Hospital	High suicidality and high psychiatric comorbidities in multiple illicit drug users call for special need for suicide screening and a more integrated care incorporating psychiatric and substance treatment.	7
2022	Toxics	Linkou Chang Gung Memorial Hospital	The mortality NPS users were older, with deep coma, faster heart rate and respiratory rate, lower blood pressures and O2 room air saturation, more seizures, abnormal breath sounds, and had urine incontinence compared to the survivor patients. The mortality patients also had acute kidney injury, higher potassium, blood sugar, liver function test, and lactate level.	8
2023	J Forensic Leg Med	Mackay Memorial Hospital	NPS users are relatively younger, are more likely to experience facial flush and palpitation and engage in more self-harm, violence, and suicide than non-NPS drug users.	9
2023	Medicine (Baltimore)	MacKay Memorial Hospital	The NPS users were significantly younger than those with negative results on toxic testing (26.4 vs 37.5, P = .005). The heart rate of NPS users was significantly faster than that of the group with negative results of toxic testing (111.1 vs 93.5 beats per minute, P = .046). The heartbeats of INPS group were also significantly faster than those with a negative result in toxicology screen (119.6 vs 93.5 beats per minute, P = .024). Those who used classical illicit drugs combined with NPS had significantly higher palpitation than those with negative results of toxic testing (27.3% vs 3.1%, P = .017).	10