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CẤP CỨU NGỘ ĐỘC V QU LIỀU OPIACS (DẪN CHẤT CỦA THUỐC PHIỆN)
                       Nguyễn Văn Bch (Mdecin urgentiste, Diplm de la Facult de Mdecine de Marseille)
                       V Khi Bửu (BS chuyn khoa 1 Nội tổng qut)
 
                                                                    
* Ngộ độc v qu liều opiacis l một cấp cứu nội khoa quan trọng cần sự can thiệp của ton cấp cứu di động ngay tại nơi xảy ra tai nạn, sau đ bệnh nhn phải được chuyển gấp đến khu cấp cứu nội khoa.
* Opiacs bao gồm những chất xuất pht từ thuốc phiện (drivs de l'opium),  những chất bn tồng hợp (semi-synthtiques), hay tổng hợp(synthtiques) c tnh chất chung l tc động ở những thụ thể thuốc phiện (rcepteurs opiacs) tại no gy nn sự phụ thuộc thuốc (nghiện) sau một thời gian sử dụng (ngoại trừ lopramide v chất nầy khng thấm qua được hng ro mu-no). Những opiacs thng thường l morphine, codine, hroine, hydromorphine, oxymorphine, mthadone, papavrine, narcotine, buprnorphine ...

* Suy h hấp cấp tnh l mối lo ngại hng đầu ở cc trường hợp ngộ độc opiacs. V thế, điều trị suy h hấp cấp tnh l trị liệu cấp cứu chủ yếu.

* Thuốc cấp cứu cần thiết: Naloxone (Narcan, Nalone, Narcanti): ống 1ml chứa 0,4 mg, dạng tim tĩnh mạch, tim bắp hoặc tim dưới da.

* Dụng cụ cấp cứu cần thiết: cc dụng cụ cấp cứu, hồi sức về tim mạch v h hấp.

* Chẩn đon:
    -Trường hợp ngộ độc đơn thuần (khng biến chứng): thường dễ chẩn đon dựa vo cc triệu chứng sau:  rối loạn tri gic (troubles de conscience), nhịp thở chậm (thường <12 lần/ pht), con ngươi thu nhỏ (myosis) (c thể nhỏ bằng đầu kim: en tte d'pingle). C thể thấy tm (cyanose). Tuy nhin, bệnh nhn cn phản ứng với kch thch đau.
    -Trường hợp ngộ độc đ c biến chứng: hn m, co giật, trụy tim mạch, thn nhiệt thấp (hypothermie), nhiễm trng phổi, ph phổi (dme pulmonaire non cardiaque), ly giải cơ (rhadomyolyse).
 
* Điều trị cấp cứu trường hợp ngộ độc đơn thuần (khng biến chứng): Chủ yếu l điều trị suy h hấp cấp tnh, bao gồm:
  . Dưỡng kh liệu php (oxygnothrapie), với mặt nạ (masque) hoặc qua ống nội kh quản (intubation), hay my thở nếu cần.
  . Điều trị đặc hiệu (traitement spcifique): dng thuốc giải độc: Naloxone.
  Về mặt thực hnh, ty theo hon cảnh v phương tiện trang bị m ưu tin cho một trong hai liệu php trn. Nn dnh ưu tin cho dưỡng kh liệu php v hiệu quả cao, t gy biến chứng. Dưỡng kh liệu php đơn độc thường gip bệnh nhn lấy lại tnh trạng tri gic (tat de conscience) một cch khả quan. Trong mọi trường hợp, mục đch  l hồi phục sự h hấp hiệu quả của bệnh nhn.
  Naloxone bao giờ cũng phải được pha long trước khi dng (pha 0,4 0,8 mg trong 10 ml trong NaCl 0,9% hay Dextrose 5%: tim  0,2 mg vo tĩnh mạch cứ mỗi 2 pht. Ngừng tim khi nhịp thở khoảng 10 12 /pht v khi c sự ti xuất hiện cc phản xạ ở đường h hấp trn đ l những phản xạ gy ra từ những kch thch vng tỵ hầu (rhino-pharynx) khi đưa 1 tubulure qua đường mũi, v vng khẩu hầu (oro-pharynx) khi dng cy đ lưỡi (abaisse-langue). Hiệu quả điều trị c thể thấy ngay 1 2 pht sau khi tim thuốc. Nếu sau khi tim 1,2 mg m vẫn khng c hiệu quả th nn bắt đầu xem xt lại chẩn đon, hy nghĩ đến những bệnh no do thiếu dưỡng kh (lsions crbrales hypoxiques), hay qu liều với nhiều thuốc hỗn hợp. C thể dng liều lượng cao hơn 1,2 mg.
 
* Cc xt nghiệm cận lm sng:
  - X quang phổi, đo lường cc kh trong mu động mạch (gazomtrie artrielle), điện tm đồ, ion đồ (ionogramme), creatinin mu ... Tuy nhin khng c xt nghiệm no l cần thiết trước khi khởi đầu cc trị liệu khẩn cấp nu trn.
 
  - Xt nghiệm phn tch chất độc c thể xc nhận c morphiniques trong nước tiểu. Tuy nhin, khng tm thấy được chất độc trong trường hợp ngộ độc buprnorphine.

  - Xt nghiệm tm cc dược chất hướng thần kinh (psychotropes) (như amphtamines, cocaine, barbituriques, benzodiazpines canabis, marjuana, haschisch...) lc no cũng cần thiết.
 
 * Ghi ch:   
    Cc trị số bnh thường của kh trong mu (Gazomtrie artrielle normale):
    - PaO2: ty thuộc vo tuổi của bệnh nhn (PaO2 tnh bằng mmHg = 104,2 - 0,27 tuổi)
    - PaCO2: 35 - 44 mmHg ;
    - Bicarbonates (HCO3) : 22 - 28 mmol/L
    - SaO2 : 95-100 %


 
Cảm ơn trước mọi gp , đng gp kinh nghiệm tri liệu  của cc bạn v đồng nghiệp, xin gởi về :
docteur_nguyen@yahoo.fr  hay  khoi1952buu@yahoo.com

 
* Ti liệu đọc thm:
(http://www.rxlist.com/narcan-drug.htm)
Naloxone hydrochloride, a narcotic antagonist, is a synthetic congener of oxymorphone. In structure it differs from oxymorphone in that the methyl group on the nitrogen atom is replaced by an allyl group.
It has the following molecular formula C19H21NO4HCl with a molecular weight of 363.84.
The chemical name for naloxone hydrochloride is: (-)-17-Allyl-4, 5a-epoxy-3,14-dihydroxymorphinan-6-one hydrochloride
Naloxone hydrochloride occurs as a white to slightly off-white powder, and is soluble in water, in dilute acids, and in strong alkali; slightly soluble in alcohol; practically insoluble in ether and in chloroform.
Naloxone Hydrochloride Injection is a sterile solution intended for intramuscular, subcutaneous or intravenous use. Each mL contains naloxone hydrochloride 400 micrograms (0.4 mg), sodium chloride 8.6 mg, methylparaben 1.8 mg and propylparaben 0.2 mg in Water for Injection. pH 3.0-4.5; hydrochloric acid and/or sodium hydroxide used, if needed, for pH adjustment. Sealed under nitrogen.
INDICATIONS
Naloxone Hydrochloride Injection is indicated for the complete or partial reversal of narcotic depression, including respiratory depression, induced by opioids including natural and synthetic narcotics, propoxyphene, methadone and the narcotic-antagonist analgesics: nalbuphine, pentazocine and butorphanol. Naloxone Hydrochloride Injection is also indicated for the diagnosis of suspected acute opioid overdosage.
DOSAGE AND ADMINISTRATION
Naloxone Hydrochloride Injection may be administered intravenously, intramuscularly, or subcutaneously. The most rapid onset of action is achieved by intravenous administration, and this route is recommended in emergency situations.
Since the duration of action of some narcotics may exceed that of naloxone, the patient should be kept under continued surveillance, and repeated doses of naloxone hydrochloride should be administered, as necessary.
Intravenous Infusion
Naloxone Hydrochloride Injection may be diluted for intravenous infusion in 0.9% Sodium Chloride Injection or 5% Dextrose Injection. The addition of 2 mg of naloxone hydrochloride in 500 mL of either solution provides a concentration of 0.004 mg/mL. Mixtures should be used within 24 hours. After 24 hours, the remaining unused solution must be discarded. The rate of administration should be titrated in accordance with the patient's response.
Naloxone Hydrochloride Injection should not be mixed with preparations containing bisulfite, metabisulfite, long-chain or high molecular weight anions, or any solution having an alkaline pH. No drug or chemical agent should be added to Naloxone Hydrochloride Injection unless its effect on the chemical and physical stability of the solution has first been established.
Usage in Adults
Narcotic Overdose-Known or Suspected: An initial dose of 0.4 mg to 2 mg of naloxone hydrochloride may be administered intravenously. If the desired degree of counteraction and improvement in respiratory functions is not obtained, it may be repeated at 2 to 3 minute intervals. If no response is observed after 10 mg of naloxone hydrochloride have been administered, the diagnosis of narcotic induced or partial narcotic induced toxicity should be questioned. Intramuscular or subcutaneous administration may be necessary if the intravenous route is not available.
Postoperative Narcotic Depression: For the partial reversal of narcotic depression following the use of narcotics during surgery, smaller doses of naloxone hydrochloride are usually sufficient. The dose of naloxone hydrochloride should be titrated according to the patient's response. For the initial reversal of respiratory depression, Naloxone Hydrochloride Injection should be injected in increments of 0.1 to 0.2 mg intravenously at two- to three- minute intervals to the desired degree of reversal, i.e., adequate ventilation and alertness without significant pain or discomfort. Larger than necessary dosage of naloxone hydrochloride may result in significant reversal of analgesia and increase in blood pressure. Similarly, too rapid reversal may induce nausea, vomiting, sweating or circulatory stress.
Repeat doses of naloxone hydrochloride may be required within one- to two-hour intervals depending upon the amount, type (i.e., short or long acting) and time interval since last administration of narcotic. Supplemental intramuscular doses have been shown to produce a longer lasting effect.
Usage in Children
Narcotic Overdose-Known or Suspected: The usual initial dose in children is 0.01 mg/kg body weight given intravenously. If this dose does not result in the desired degree of clinical improvement, a subsequent dose of 0.1 mg/kg body weight may be administered. If an intravenous route of administration is not available, Naloxone Hydrochloride Injection may be administered intramuscularly or subcutaneously in divided doses. If necessary, Naloxone Hydrochloride Injection can be diluted with Sterile Water for Injection.
Postoperative Narcotic Depression: Follow the recommendations and cautions under Usage in Adults - Postoperative Narcotic Depression (above). For the initial reversal of respiratory depression, naloxone hydrochloride should be injected in increments of 0.005 mg to 0.01 mg intravenously at two- to three-minute intervals to the desired degree of reversal.
Usage in Neonates
When using naloxone hydrochloride injection in neonates, a product containing 0.02 mg/mL should be used.
Narcotic-Induced Depression: The usual initial dose is 0.01 mg/kg body weight administered intravenously, intramuscularly or subcutaneously. This dose may be repeated in accordance with adult administration guidelines for postoperative narcotic depression.
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
HOW SUPPLIED
Naloxone Hydrochloride Injection is available in the following packages:
0.4 mg/mL
1 mL DOSETTE ampuls packaged in 10s (NDC 0641-1451-33)
1 mL DOSETTE vials packaged in 10s (NDC 0641-0442-23)
10 mL Multiple Dose vials packaged individually (NDC 0641-2521-41)
STORAGE
Protect from light Store at controlled room temperature 15- 30 C ( 59- 86 F).
SIDE EFFECTS
Abrupt reversal of narcotic depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures and cardiac arrest In postoperative patients, larger than necessary dosage of naloxone hydrochloride may result in significant reversal of analgesia and in excitement
Hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been associated with the use of naloxone hydrochloride postoperatively (see PRECAUTIONS and DOSAGE AND ADMINISTRATION: Usage in Adults - Postoperative Narcotic Depression).
DRUG INTERACTIONS
No information provided.
WARNINGS
Naloxone Hydrochloride Injection should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on oploids. In such cases, an abrupt and complete reversal of narcotic effects may precipitate an acute abstinence syndrome.
The patient who has satisfactorily responded to naloxone should be kept under continued surveillance and repeated doses should be administered, as necessary, since the duration of action of some narcotics may exceed that of naloxone.
Naloxone is not effective against respiratory depression due to non-opiold drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respirations should be mechanically assisted.
PRECAUTIONS
In addition to Naloxone Hydrochloride Injection, other resuscitative measures, such as maintenance of a free airway, artificial ventilation, cardiac massage and vasopressor agents should be available and employed, when necessary, to counteract acute narcotic poisoning.
Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, and pulmonary edema have been reported. These have occurred in postoperative patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, Naloxone Hydrochloride Injection should be used with caution in patients with pre-existing cardiac disease or patients who have received potentially cardiotoxic drugs.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenicity and mutagenicity studies have not been performed with naloxone hydrochloride. Reproductive studies in mice and rats demonstrated no impairment of fertility.
Pregnancy
Teratogenlc Effects - Pregnancy Category B. Reproduction studies have been performed in mice and rats at doses up to 1000 times the human dose and have revealed no evidence of impaired fertility or harm to the fetus due to naloxone hydrochloride. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Naloxone Hydrochloride Injection is administered to a nursing woman.
OVERDOSE
There is no clinical experience with naloxone hydrochloride overdosage in humans.
In the mouse and rat, the intravenous LD50 is 150 5 mg/kg and 109 4 mg/kg, respectively. In acute subcutaneous toxicity studies in newborn rats, the LD50 (95% CL) is 260 (228-296) mg/kg. Subcutaneous injection of 100 mg/kg/day in rats for 3 weeks produced only transient salivation and partial ptosis following injection; no toxic effects were seen at 10 mg/kg/day for 3 weeks.
CONTRAINDICATIONS
Naloxone Hydrochloride Injection is contraindicated in patients known to be hypersensitive to it.
CLINICAL PHARMACOLOGY
Naloxone prevents or reverses the effects of opioids including respiratory depression, sedation and hypotension. Also, it can reverse the psychotomimetic and dysphoric effects of agonist-antagonists such as pentazocine.
Naloxone hydrochloride is an essentially pure narcotic antagonist, i.e., it does not possess the "agonistic" or morphinelike properties characteristic of other narcotic antagonists; naloxone hydrochloride does not produce respiratory depression, psychotomimetic effects or pupillary constriction. In the absence of narcotics or agonistic effects of other narcotic antagonists, it exhibits essentially no pharmacologic activity.
In the presence of physical dependence on narcotics, naloxone will produce withdrawal symptoms; it has not been shown to produce tolerance nor to cause physical or psychological dependence.
Mechanism of Action
While the mechanism of action of naloxone is not fully understood, the preponderance of evidence suggests that naloxone antagonizes the oploid effects by competing for the same receptor sites.
When Naloxone Hydrochloride Injection is administered intravenously, the onset of action is generally apparent within two minutes; the onset of action is only slightly less rapid when it is administered subcutaneously or intramuscularly. The duration of action is dependent upon the dose and route of administration of naloxone hydrochloride. Intramuscular administration produces a more prolonged effect than intravenous administration. The requirement for repeat doses of naloxone hydrochloride, however, will also be dependent upon the amount, type and route of administration of the narcotic being antagonized.
Following parenteral administration, naloxone hydrochloride is rapidly distributed in the body. It is metabolized in the liver, primarily by glucuronide conjugation and excreted in urine. In one study, the serum half-life in adults ranged from 30 to 81 minutes (mean 64 12 minutes). In a neonatal study, the mean plasma half-life was observed to be 3.1 0.5 hours.
PATIENT INFORMATION
See WARNINGS, PRECAUTIONS and CONTRAINDICATIONS.