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*For reference by medical professionals
only, the highest incidence of antimicrobials and adrenal glucocorticoid
hiccups (diaphragmatic spasm) is due to local diaphragm, phrenic nerve, The vagus nerve or the central nervous system above the cervical medulla 3~5 is stimulated, causing paroxysmal spasm of one or both diaphragms, accompanied by sudden closure of the glottis during inhalation, making a special sound
.
Lasting more than 48 hours is called recalcitrant hiccups
.
Hiccups can be divided into central, peripheral, and other causes (eg, drugs, systemic paralysis, postoperative surgery, psychiatric factors) [1].
This article only summarizes the research progress at home and abroad on drug-induced hiccups and their prevention and treatment for clinical reference
.
, such as stimulants, sulfonamides, dexamethasone, chlordiazepoxide, methyldopa, barbiturates, diazepam, etc.
[2].
In recent years, literature analysis has found that there are 75 drugs that cause hiccups, among which the highest incidence is antimicrobial drugs and adrenal glucocorticoids (GC) [3].
to cause hiccups.
Penicillin-induced hiccups may be related to excessive dosage and excessive intravenous drip concentration; The mechanism of cephalosporin hiccups may be that cephalosporins stimulate gastrointestinal nerve reflexes to cause hiccups; Imipenem cilastatin affects γ-aminobutyric acid receptors in the brain, resulting in decreased inhibition of the hiccup reflex arc by higher nerve centers, leading to hiccups [4].
The mechanism of hiccups caused by gentamicin may be related to complexing calcium ions in the body[5].
Hiccups caused by lincomycin may be related to
vagus nerve excitation and acetylcholine release due to short-term increase in lincomycin levels in the blood.
On the one hand, acetylcholine binds to parasympathetic M receptors to produce M-like effects, which constricts the gastrointestinal tract and leads to gastrointestinal nerve dysfunction; On the other hand, it binds to the N of the diaphragm to produce an N-like effect, causing the diaphragm to contract, resulting in diaphragm spasm and hiccups [6].
The causes of clindamycin hiccups may be: (1) the excitation of the hiccups reflex arc during intravenous infusion of clindamycin stimulates the diaphragm to cause spasm, and hiccups symptoms occur; (2) a special symptom of clindamycin allergy; (3) Individual differences [7].
The cause of recalcicycline causing recalcitrant hiccups is not clear, and may be related to the following factors: (1) impurities such as β-doxycycline, metacycline, 4-epidoxycycline, and oxytetracycline can be produced during the production of drugs, which induce hiccups after entering the body with drugs; (2) Doxycycline hydrochloride for injection enters the body as an allergen and causes allergic reactions, causing hiccups; (3) Related to individual differences, patients tolerate the drug poorly, and after the drug enters the body, the sensitivity to adverse reactions increases
.
The specific mechanism needs to be further studied [8].
The cause of hiccups caused by quinones may be related to the drug's impact on the hiccup center at the base of the fourth ventricle of the medulla oblongata [9].
It is speculated that the occurrence of intractable hiccups caused by voriconazole may be the cause of neurological disorders, resulting in diaphragmatic spasm due to abnormal discharge after stimulation of the phrenic nerve or vagus nerve [9].
incidence.
The cause of hiccups caused by dexamethasone is related to dexamethasone promoting increased secretion of gastric acid and pepsin, which in turn stimulates the vagus nerve of the gastrointestinal tract and excites the phrenic nerve, resulting in diaphragmatic spasm
.
In addition, it is also related to the fact that this product can increase the excitability of the central nervous system, affect the number of adrenergic receptors on the cell surface and the receptor-mediated intracellular information transmission process, increase receptor sensitivity, affinity and diaphragm contractility [10].
It has also been suggested that synthetic GC is hindered by P-glycoprotein in the blood-brain barrier and has difficulty entering the brain, while large doses of dexamethasone activate receptors
in hippocampal tissue and hypothalamus.
Dexamethasone has a higher chance of hiccups than other varieties of GC, which may be related to the fluorine content in its chemical structure [11].
.
Among them, the causes of hiccups caused by cisplatin may be: (1) neuropsychological stress response; (2) Chemotherapy drugs directly cause gastrointestinal mucosal damage, affect food digestion, and even gastrointestinal gas accumulation, directly cause increased vagus nerve tone and diaphragm spasm; (3) Chemicals that stimulate tumor necrosis after chemotherapy [12].
.
These include antipsychotics (aripiprazole, olanzapine, clozapine, risperidone, diazepam, quetiapine, fluoxetine), cardiovascular system medications (dobutamine, cinepazide, captopril, nimodipine, arrhythmine, pibedil, monosialic acid tetrahexose ganglioside ester, galantamine, calf serum deproteinization injection), digestive system medications (Ondansetron, tropisetron, hepatic injection).
Other drugs that cause hiccups include iopromide, aminophylline, brohexin, posterior pituitary hormone, mannitol, lidocaine, ketamine, risedronate sodium, nimesulide, Shengbaineng energy, Xiyanping, double huanglian injection and some Chinese medicines (Junzi, nephrolithi punch, andrographis drop pills, compound licorice tablets, vitamin C silver warp tablets).
of drug-induced hiccups often occur 10min~14d after administration, and occur in the infusion process or ≤30min
.
Patients with hiccups in the course of drug treatment should be diagnosed
early based on their drug history, previous drug-induced hiccups, and drug types.
The treatment of drug-induced hiccups mainly includes etiological treatment and symptomatic treatment, and commonly used therapies include drugs, vagus nerve disturbance or stimulation, and surgical treatment
.
Domperidone, metoclopramide, baclofen, chlorpromazine, haloperidol, antiepileptic drugs (eg, sodium valproate, gabapentin, carbamazepine), calcium antagonists (eg, nifedipine, nimodipine), proton pump inhibitors, and central stimulants are used for drug treatment (such as methylphenidate), anesthetic drugs (such as lidocaine, propofol, etc.
) [2].
Among them, chlorpromazine is currently the only drug approved by the US Food and Drug Administration for the treatment of hiccups, which can be injected intramuscularly or orally [13].
Drug treatment for refractory hiccups has been widely
reported in recent years.
For example, oral administration of etholisone [14,15], nifedipine tablets [16], sodium valproate and other drugs can relax muscles, relieve diaphragm spasm, and stop hiccups
.
Eethyl risone is a central muscle relaxant, and is banned
for severe liver and kidney dysfunction, accompanied by shock, and lactating women.
Sodium valproate treatment hiccups 0.
2 g/time, 3~4 times/d, gradually increased until the seizure
is controlled.
Some [17] believe that the effective dose of sodium valproate for hiccups varies greatly
from individual to individual.
Acupoint drug injection, such as Neiguan, Zusanli injection of 654-2 or atropine, etc.
, can also be intramuscular injection or intravenous infusion of lidocaine [18] and intramuscular injection of vitamin K3
.
Among them, the mechanism of lidocaine in the treatment of hiccups may be related to its blocking effect on peripheral and central nerve conduction [19], but patients with liver and kidney dysfunction should be used with caution on lidocaine [20], vitamin K3 can relieve smooth muscle spasm, good effect, few side effects
。
Phrenic nerve block is one of the clinical treatment methods, with good efficacy [21], phrenic nerve block can block the hiccup nerve reflex arc, so that the diaphragm spasm can be relieved and achieve the purpose of
treatment.
In the treatment, 1% lidocaine is mainly used to block the phrenic nerve sensory fibers, so that the hiccup reflex arc is interrupted, preventing the occurrence of hiccups, but the motor fibers of the phrenic nerve are very weak, do not affect the respiratory muscles, thus not affecting the patient's breathing, can achieve the purpose of treatment
.
Where to see more neurological knowledge?
Come to the "doctor's station" and take a look 👇
only, the highest incidence of antimicrobials and adrenal glucocorticoid
hiccups (diaphragmatic spasm) is due to local diaphragm, phrenic nerve, The vagus nerve or the central nervous system above the cervical medulla 3~5 is stimulated, causing paroxysmal spasm of one or both diaphragms, accompanied by sudden closure of the glottis during inhalation, making a special sound
.
Lasting more than 48 hours is called recalcitrant hiccups
.
Hiccups can be divided into central, peripheral, and other causes (eg, drugs, systemic paralysis, postoperative surgery, psychiatric factors) [1].
This article only summarizes the research progress at home and abroad on drug-induced hiccups and their prevention and treatment for clinical reference
.
01
There are many kinds of drugs that can cause hiccups in drug-induced hiccups and their mechanisms, such as stimulants, sulfonamides, dexamethasone, chlordiazepoxide, methyldopa, barbiturates, diazepam, etc.
[2].
In recent years, literature analysis has found that there are 75 drugs that cause hiccups, among which the highest incidence is antimicrobial drugs and adrenal glucocorticoids (GC) [3].
01
Antimicrobials amoxicillin, mezlocillin, penicillin, imipenem cilastatin, ampicillin, cephalexin, ceftriaxone, cefotaxime, cefoxitin, cefoxime, cefoxitin, cefazolelin, cefoperazone, gentamicin, erythromycin, lincomycin, clarithromycin, clindamycin, roxithromycin, ofloxacin, levofloxacin, ciprofloxacin, metronidazole, tinidazole, oxytetracycline, doxycycline, praziquantel, voriconazole, arabinosine, Albendazole and others have been reportedto cause hiccups.
Penicillin-induced hiccups may be related to excessive dosage and excessive intravenous drip concentration; The mechanism of cephalosporin hiccups may be that cephalosporins stimulate gastrointestinal nerve reflexes to cause hiccups; Imipenem cilastatin affects γ-aminobutyric acid receptors in the brain, resulting in decreased inhibition of the hiccup reflex arc by higher nerve centers, leading to hiccups [4].
The mechanism of hiccups caused by gentamicin may be related to complexing calcium ions in the body[5].
Hiccups caused by lincomycin may be related to
vagus nerve excitation and acetylcholine release due to short-term increase in lincomycin levels in the blood.
On the one hand, acetylcholine binds to parasympathetic M receptors to produce M-like effects, which constricts the gastrointestinal tract and leads to gastrointestinal nerve dysfunction; On the other hand, it binds to the N of the diaphragm to produce an N-like effect, causing the diaphragm to contract, resulting in diaphragm spasm and hiccups [6].
The causes of clindamycin hiccups may be: (1) the excitation of the hiccups reflex arc during intravenous infusion of clindamycin stimulates the diaphragm to cause spasm, and hiccups symptoms occur; (2) a special symptom of clindamycin allergy; (3) Individual differences [7].
The cause of recalcicycline causing recalcitrant hiccups is not clear, and may be related to the following factors: (1) impurities such as β-doxycycline, metacycline, 4-epidoxycycline, and oxytetracycline can be produced during the production of drugs, which induce hiccups after entering the body with drugs; (2) Doxycycline hydrochloride for injection enters the body as an allergen and causes allergic reactions, causing hiccups; (3) Related to individual differences, patients tolerate the drug poorly, and after the drug enters the body, the sensitivity to adverse reactions increases
.
The specific mechanism needs to be further studied [8].
The cause of hiccups caused by quinones may be related to the drug's impact on the hiccup center at the base of the fourth ventricle of the medulla oblongata [9].
It is speculated that the occurrence of intractable hiccups caused by voriconazole may be the cause of neurological disorders, resulting in diaphragmatic spasm due to abnormal discharge after stimulation of the phrenic nerve or vagus nerve [9].
02
GC that causes hicc includes dexamethasone, methylprednisolone, prednisone, hydrocortisone, and betamethasone, with dexamethasone being the highestincidence.
The cause of hiccups caused by dexamethasone is related to dexamethasone promoting increased secretion of gastric acid and pepsin, which in turn stimulates the vagus nerve of the gastrointestinal tract and excites the phrenic nerve, resulting in diaphragmatic spasm
.
In addition, it is also related to the fact that this product can increase the excitability of the central nervous system, affect the number of adrenergic receptors on the cell surface and the receptor-mediated intracellular information transmission process, increase receptor sensitivity, affinity and diaphragm contractility [10].
It has also been suggested that synthetic GC is hindered by P-glycoprotein in the blood-brain barrier and has difficulty entering the brain, while large doses of dexamethasone activate receptors
in hippocampal tissue and hypothalamus.
Dexamethasone has a higher chance of hiccups than other varieties of GC, which may be related to the fluorine content in its chemical structure [11].
03
Antineoplastic drugs that cause hiccups include oxaliplatin, cisplatin, doxorubicin, and paclitaxel.
Among them, the causes of hiccups caused by cisplatin may be: (1) neuropsychological stress response; (2) Chemotherapy drugs directly cause gastrointestinal mucosal damage, affect food digestion, and even gastrointestinal gas accumulation, directly cause increased vagus nerve tone and diaphragm spasm; (3) Chemicals that stimulate tumor necrosis after chemotherapy [12].
04
Other drugs, other drugs, the mechanism of hiccups caused by other drugs is not clear.
These include antipsychotics (aripiprazole, olanzapine, clozapine, risperidone, diazepam, quetiapine, fluoxetine), cardiovascular system medications (dobutamine, cinepazide, captopril, nimodipine, arrhythmine, pibedil, monosialic acid tetrahexose ganglioside ester, galantamine, calf serum deproteinization injection), digestive system medications (Ondansetron, tropisetron, hepatic injection).
Other drugs that cause hiccups include iopromide, aminophylline, brohexin, posterior pituitary hormone, mannitol, lidocaine, ketamine, risedronate sodium, nimesulide, Shengbaineng energy, Xiyanping, double huanglian injection and some Chinese medicines (Junzi, nephrolithi punch, andrographis drop pills, compound licorice tablets, vitamin C silver warp tablets).
02
Prevention and treatmentof drug-induced hiccups often occur 10min~14d after administration, and occur in the infusion process or ≤30min
.
Patients with hiccups in the course of drug treatment should be diagnosed
early based on their drug history, previous drug-induced hiccups, and drug types.
The treatment of drug-induced hiccups mainly includes etiological treatment and symptomatic treatment, and commonly used therapies include drugs, vagus nerve disturbance or stimulation, and surgical treatment
.
Domperidone, metoclopramide, baclofen, chlorpromazine, haloperidol, antiepileptic drugs (eg, sodium valproate, gabapentin, carbamazepine), calcium antagonists (eg, nifedipine, nimodipine), proton pump inhibitors, and central stimulants are used for drug treatment (such as methylphenidate), anesthetic drugs (such as lidocaine, propofol, etc.
) [2].
Among them, chlorpromazine is currently the only drug approved by the US Food and Drug Administration for the treatment of hiccups, which can be injected intramuscularly or orally [13].
Drug treatment for refractory hiccups has been widely
reported in recent years.
For example, oral administration of etholisone [14,15], nifedipine tablets [16], sodium valproate and other drugs can relax muscles, relieve diaphragm spasm, and stop hiccups
.
Eethyl risone is a central muscle relaxant, and is banned
for severe liver and kidney dysfunction, accompanied by shock, and lactating women.
Sodium valproate treatment hiccups 0.
2 g/time, 3~4 times/d, gradually increased until the seizure
is controlled.
Some [17] believe that the effective dose of sodium valproate for hiccups varies greatly
from individual to individual.
Acupoint drug injection, such as Neiguan, Zusanli injection of 654-2 or atropine, etc.
, can also be intramuscular injection or intravenous infusion of lidocaine [18] and intramuscular injection of vitamin K3
.
Among them, the mechanism of lidocaine in the treatment of hiccups may be related to its blocking effect on peripheral and central nerve conduction [19], but patients with liver and kidney dysfunction should be used with caution on lidocaine [20], vitamin K3 can relieve smooth muscle spasm, good effect, few side effects
。
Phrenic nerve block is one of the clinical treatment methods, with good efficacy [21], phrenic nerve block can block the hiccup nerve reflex arc, so that the diaphragm spasm can be relieved and achieve the purpose of
treatment.
In the treatment, 1% lidocaine is mainly used to block the phrenic nerve sensory fibers, so that the hiccup reflex arc is interrupted, preventing the occurrence of hiccups, but the motor fibers of the phrenic nerve are very weak, do not affect the respiratory muscles, thus not affecting the patient's breathing, can achieve the purpose of treatment
.
References:
[1] Jeon Y S，Kearney A M，Baker P G.
Management of hiccups in palliative care patients［J］.
BMJ Support Palliat Care，2018，8（1）：1-6.
[2] XU Jingwei, DAI Wei, GE Junling, et al.
Research progress on pathogenesis and diagnosis and treatment strategies of hiccups[J].
Chinese Medical Journal,2017,52(6):17-20.
)
[3] PENG Qiuyan, ZHANG Jie.
Literature analysis of drug-induced hiccups[J].
Tianjin Pharmaceutical Science,2022,34(2):36-40.
)
[4] LI Lin.
Imipenem cilastatin sodium for injection-induced hiccupsis: 1 case[J].
Chinese Journal of Drug Application and Monitoring,2019,16(2):122-123.
)
[5] TANG Mingqiang.
Review of clinical data of drug-induced hiccups[J].
Medical Theory & Practice,2007,20(11):1271-1274.
)
[6] Ju Tingxue, Zhao Hong, Pan Xiaofang.
2 cases of lincomycin-induced refractory hiccups[J].
People's Military Doctor,2012,63(5):453.
)
[7] Xu Rongxing.
Clindamycin-induced hiccups: 1 case[J].
New Medical Journal,2012,43(3):150-151.
)
[8] FANG Kan, LV Guanghui.
Doxycycline hydrochloride for injection-induced hiccups: 1 case[J].
Journal of Pharmacoepidemiology,2021,30(2):143-144.
)
[9] Sheng Jiaqi, Wang Huali.
1 case of 2 episodes of hiccups caused by fluoroquinones[J].
Western Medical Journal,2003,1(3):238-238.
)
[9] HAN Junfeng, SHEN Zhongyang.
Voriconazole caused refractory hiccups: 1 case[J].
Chinese Journal of Hospital Pharmacy,2014,34(15):1325.
)
[10] XIAN Xiaoqing, BU Yanli, LI Chengjian.
A literature overview of dexamethasone-induced hiccups[J].
Chinese Journal of Drug Abuse Prevention and Control,2015,21(6):338,355.
)
XIONG Jianqun, GAO Xiaobo, HE Zhen, et al.
Literature analysis of 688 cases of drug-induced hiccups[J].
China Pharmaceutical Industry,2015,24(24):195-196.
)
[12] WANG Yang, LIU Gang, WAN Lixin.
Analysis of the causes of hiccups caused by chemotherapy drugs[J].
Modern Health Care Medical Innovation Research,2008,5(9):85.
)
[13] Kang J H，Hui D，Kim M J，et al.
Corticosteroid rotation to alleviate dexamethasone-induced hiccup：A case series at a single institution［J］.
Pain and Symptom Management，2012，43（3）：625-630.
[14] FAN Lijing, DU Zhongde, WANG Huaiming, et al.
Miona treated 16 cases of recalcitrant hiccups.
China Medical Journal of Coal Industry,2001,4(4):300-301.
[15] Fu Wen'an.
Eethyl risone for recalcitrant hiccups.
Chinese Journal of New Drug and Clinical Practice,2005,24(4):311-313.
[16] CHEN Ying.
Clinical report of 67 cases of nifedipine in the treatment of hiccups[J].
Medical Theory & Practice,2008,21(8):943-944.
)
[17] ZHANG Jingjun, CHEN Qing.
Efficacy of sodium valproate in the treatment of hiccups[J].
Chinese Journal of Geriatrics,2000,19(3):227.
)
[18] Fu Qiang.
Clinical observation of lidocaine in the treatment of hiccups[J].
Clinical Convergence,1994,9(2):69.
)
[19] Zhang Baohua, Song Min.
Lidocaine acupoint injection in the treatment of recalcitrant hiccups in stroke in 30 cases[J].
Henan Journal of Practical Neurological Diseases,2000(6):75-76.
)
[20] Yang Baofeng.
Pharmacology.
8th edition.
Beijing:People's Medical Publishing House,2013:195-196.
]
[21] Chen Kongli, Marseille.
Diaphrenic nerve block plus acupoint injection for the treatment of refractory hiccups: 28 cases[J].
Fujian Journal of Traditional Chinese Medicine,2009,40(3):31.
)
Where to see more neurological knowledge?
Come to the "doctor's station" and take a look 👇
