A Case of Severe Puffer Fish Poisoning: The Best Time to Establish Artificial Airway


 Background Puffer fish poisoning is one of the main causes of death from food poisoning in China. Currently, there is still no effective treatment method. The establishment of artificial airway and early implementation of mechanical ventilation are crucial to the prognosis of patients, but the optimal time is still not clear. Case Presentation A 62-year-old male patient complained of ‘numbness around the mouth for 3 hours after eating puffer fish’ was admitted to the emergency department, he was performed gastric lavage in time, but did not be performed protective endotracheal intubation.His condition worsen rapidly and respiratory and cardiac arrest was quickly occurred.He received aggressive treatment in the ICU, but still did not regain spontaneous breathing. Conclusion The establishment of artificial airway and early implementation of mechanical ventilation are crucial for the prognosis of patients,and we provide possible principles for performing endotracheal intubation.


Background
Puffer sh is a valuable food among asian cultures and is safe for regular use in some countries (such as Japan) [1], but tetrodotoxin (TTX) in it may still cause human poisoning if not properly cooked [1][2][3].TTX has posed a threat to human health in asian countries and has spread to the Paci c and Mediterranean regions due to global sea temperature rise [2,3]. In China, puffer sh poisoning is also one of the main causes of death from food poisoning [4].TTX is one of the most powerful neurotoxins known to cause death in patients due to respiratory or heart failure [2,3,5].Mechanical ventilation is a key measurement for the treatment of severe puffer sh poisoning [2,5]. However, when to establish arti cial airway is still unclear.This paper intends to explore the best time to establish arti cial airway through reviewing a case of severe puffer sh poisoning.

Case Presentation
The 62-year-old male patient was admitted to the emergency department at 21:25 on December 23, 2019 ,complained of 'numbness around the mouth for 3 hours after eating puffer sh'.The patient ate puffer sh (a piece of sh and liver, a bowl of sh soup) at around 19:00 on that day. After about half an hour, he developed numbness around his mouth and gradually developed numbness in his tongue and limbs. He had no dyspnea, speech disorder, swallowing di culty, body movement disorder, dizziness and headache.He had eaten puffer sh for many times in the past few years without any uncomfortable symptoms. He had a history of gout, and the treatment was unknown. He denyed the history of hypertension, diabetes, coronary heart disease and other diseases, and denyed the history of food and drug allergy.Vitals: body temperature: 36.3℃, pulse rate: 128 beats/min, respiratory rate: 20 beats/min, blood pressure: 148/78 mmHg, pulse oxygen saturation: 99%.He was sanity, uent speech, and his bilateral nasolabial sulci was symmetrical. He was clear to auscultation of both lungs, and no rhonchus or moist rhonchus. His heart rhythm was normal, and no pathologic murmurs.His abdomen was soft ,and no tenderness or rebounding pain.No edema was found in both lower limbs.The attending doctor immediately gave him gastric lavage treatment and a monitoring was made.The patient felt uncomfortable during gastric lavage. The gastric lavage tube was removed at 21:40, and the patient complained of numbness of the tongue and was vague in his speech.During this period, monitoring showed that the patient's heart rate was between 118-130 beats/min, respiratory rate was between 20-30 beats/min, blood pressure was between 140/80-189/110 mmHg, and pulse oxygen saturation was between 98%-99%.At 22:30,gastric lavage treatment was made again, but he was sudden loss of consciousness with blausucht at 22:44, and his artery pulse disappeared. The attending doctor checked the mouth of the patient and no vomit were found.Cardiopulmonary resuscitation (CPR) was immediately started, and he was admitted to intensive care unit (ICU) for further treatment.After resuscitation, emergency bedside echocardiography showed no abnormal ventricular segmental motion and no pericardial effusion.No lung exudation, pneumothorax and other lesions were found on emergency chest radiographs.Emergency laboratory tests showed that white blood cell(WBC), red blood cell(RBC) and platelet counts were in the normal range.Liver and kidney function and electrolyte were basically normal.Both the hypersensitive troponin T (hs-cTnT) and troponin I (TnI) were in the normal range.During his stay in ICU, he was given comprehensive treatment such as blood perfusion, catharsis, neurotrophic therapy, brain cell protection therapy, anti-oxidation, correct acidosis, uid replenishment, electrolyte correction, and anti-infection. The patient was still in coma and failed to recover from spontaneous breathing. He was transferred to another hospital for hyperbaric oxygen treatment on December 31, 2019. Disscussion A poison isolated from the ovaries of puffer sh by Dr. Yoshizumi Tahara in 1894 was named TTX in 1909 [2,6].TTX is mainly found in the liver and ovaries of puffer sh. It binds to the sodium channels of human excitable tissues (muscles and nerves), inhibits the in ux of sodium ions, affects the generation of action potentials and impulse conduction, and causes paralysis of nerves and muscles [2,3,[5][6][7][8].The severity of symptoms caused by TTX is related to dose and individual differences [2,3,8].Symptoms usually appear within 30 minutes to 6 hours after eating [2,5,7], TTX is excreted from urine within 8 hours [5,7], and symptoms recover within 24 hours [2].However, people who intakes large numbers of puffer sh can become ill within 30 minutes [5,8].Fukuda ranks fugu poisoning at four grades based on symptoms:Grade 1 is neuromuscular symptoms(perioral paresthesia, headache, sweating, pupil constriction) and mild gastrointestinal symptoms(nausea, vomiting, excessive salivation, hematemesis, diarrhea, abdominal pain);Grade 2 is paresthesia extending to the trunk and limbs, early motor paralysis and lack of coordination;Grade 3 is neuromuscular symptoms worsen, dysarthria, dysphagia, sleepiness, ataxia, oating feeling, cranial nerve palsy, muscle tremor, etc.), heart/lung symptoms (low blood pressure, or hypertension, vasomotor dysfunction, cardiac arrhythmias, cyanosis, pale, di culty breathing, etc.), skin symptoms (bruises, exfoliative dermatitis, blisters), hypotension and aphasia;Grade 4 is delirium, respiratory paralysis, severe hypotension, and arrhythmia [2,5,7,8].Generally, grade 3 and grade 4 are considered as severe puffer sh poisoning [5,7].
Currently, there is no speci c treatment for puffer sh poisoning. For patients with severe puffer sh poisoning, timely establishment of arti cial airway and implementation of mechanical ventilation is the key to treatment [2,5,7,8].It is important to note that although there is conscious and spontaneous breathing,the severe globe sh sh poisoning patients do not appear to breathe myoparalysis at rst, but may have the decrease of the tidal volume and minute ventilation and insu cient ventilation because of strength decline [5].So, taking protective endotracheal intubation, or establishmenting of arti cial airway, and early implementation of mechanical ventilation is very important.In general, the indications for protective endotracheal intubation are as follows: 1.Coma patients, especially those at risk of inhalation;2. Patients with obvious changes in autonomic respiratory rate and rhythm;3.Patients with cerebral hernia may cause respiratory and cardiac arrest;4.Patients with serious condition and will deteriorates rapidly, which may lead to respiratory and cardiac arrest;5. Patients who requiring prolonged mechanical ventilation due to severe hypoxemia or hypercapnia or other reasons;6. Patients with large-scale trauma of the whole body, especially those who with severe brain injury [9,10].However, protective endotracheal intubation is associated with pneumonia, length of ICU stay, death and cost [11]. In addition, for patients with mild poisoning, due to their spontaneous breathing, muscle relaxants are needed to establish arti cial airway, which may aggravate the risk of respiratory muscle paralysis and cause medical disputes.Therefore, it is extremely important to know the best time to establish an arti cial airway.
In this case, the patient was diagnosed as grade 1-2 puffer sh poisoning according to the symptoms at the time of admission. We performed gastric lavage in time, but did not perform protective endotracheal intubation. However, the patient's condition progressed rapidly and respiratory and cardiac arrest quickly occurred.The patient had no underlying heart disease, the cardiac marker troponin was normal after resuscitation, and no segmental ventricular wall motion abnormalities were found on echocardiography. We believed that acute myocardial infarction could be excluded, and pericardial effusion and cardiac tamponin could be excluded on echocardiography.After receiving the diagnosis, the patient found high blood pressure, but no chest pain, abdominal pain, etc.Echocardiography did not indicate aortic widening, blood pressure was stable during the ICU hospitalization, and there was no evidence of aortic dissection.During gastric lavage, the patient had cardiac and respiratory arrest. However, we checked that there was no vomit or secretions in the oral cavity, so there was little possibility of suffocation.The patient had no history of pulmonary basic diseases, and no pulmonary exudative lesions and pneumothorax were found on chest radiographs, acute respiratory distress syndrome and pneumothorax could be rull out.The patient had good normal activities,and echocardiography showed no signs of right ventricle enlargement or pulmonary hypertension, so the possibility of pulmonary embolism was also low.After the patient arrived at the hospital, his symptoms worsened, from numbness around the mouth to the tongue and slurred words, and nally cardiac and respiratory arrest occured. Based on the above analysis, we believed that his cardiac and respiratory arrest was caused by acute puffer sh poisoning.The patient had a poor prognosis. We re ected on the treatment process of the case and believed that the establishment of arti cial airway as early as possible might be helpful to the prognosis of the patient.Therefore, we believe that the timing of the establishment of arti cial airway in puffer sh poisoning patients should be determined according to the severity of the disease, the speed of disease progression, the risk of deterioration, and the basic condition of the patients. Speci c indications are as follows: 1.Patients with grade 3 or above of Futian poisoning should establish an arti cial airway immediately;2. Symptoms of poisoning occur in a short time, especially in patients with symptoms within 30 minutes after eating.3. For grade-1 patients who progress rapidly to grade-2 during treatment or still progress after active treatment for 6-8 hours, an arti cial airway should be established immediately;4. Patients who eat the liver or ovaries of puffer sh, eat large amounts of sh, or drink alcohol at the same time should establish arti cial airway immediately, no matter what grade they are at at the time of treatment;5. Arti cial airway should be established before gastric lavage in patients with previous basic diseases such as cerebrovascular disease and risk of aspiration;6. Arti cial airway should be established immediately in elderly patients or patients with liver and kidney dysfunction, which may lead to toxin metabolism disorder or delayed excretion.In addition to the above, all patients should assume that an arti cial airway needs to be established urgently, and prepare the personnel and materials for the establishment of the arti cial airway in advance.

Conclusion
In conclusion, puffer sh poisoning is one of the main causes of death caused by food poisoning in China. Currently, there is still no speci c treatment method. The establishment of arti cial airway and early implementation of mechanical ventilation are crucial for the prognosis of patients,and we provide possible principles for performing endotracheal intubation.

Consent for publication
Written informed consent for publication of the clinical details was obtained from the patient.

Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Competing interests
The authors declare that they have no competing interests.

Corresponding author
Correspondence to Siqi Zhu Authors' contributions SQZ had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis;SQZ, YY participated in the treatment of this patient and were involved in the development of the conclusions. SQZ,XRF collected all datas; SQZ wrote the rst draft with assistance from YY and ZF ,and SQZ edited the nal draft. QDZ made critical revision of the article for important intellectual content. All authors agreed with the results and conclusions of this article. All authors read and approved the nal manuscript.