Management of Opioid Analgesic Overdose

Management of Opioid Analgesic Overdose from Sun YaiCheng

Management of Opioid Analgesic Overdose

N Engl J Med 2012;367:146-55

Clinical Manifestations

The classic toxidrome of apnea, stupor, and miosis suggests the diagnosis of opioid toxicity

Diagnosis

Physical examination (hypopnea or apnea, miosis, and stupor) should lead the clinician to consider the diagnosis of opioid analgesic overdose.
Quantitative measures of drug concentrations are useless in cases of overdose.

Management

Patients with apnea need a pharmacologic or mechanical stimulus in order to breathe.

Naloxone

• onset <2 minutes (IV)
• duration 20 to 90 minutes
• Once the respiratory rate improves after the administration of naloxone, the patient should be observed for 4 to 6 hours before discharge is considered.

Decision Tree for Managing Opioid Analgesic Overdose in Adults.

葡萄催芽劑中毒

奪命晚餐 4人暴斃 死狀詭異
「沒見過這麼離奇的案子」

2011年 7月7日 蘋果日報  

情殺奪4命 南投神祕中毒大逆轉

2011年 8月23日 蘋果日報  

ETHYLENE CHLOROHYDRIN

Ethylene chlorohydrin, a cellulose ester solvent, is a colorless liquid with an odor resembling a mixture of ethyl alcohol and ether. Ethylene chlorohydrin is used as a solvent in industry. 

In agriculture, it is used to speed up sprouting of potatoes, to treat seeds to inhibit biological activity, and to hasten grape germination.

CLINICAL EFFECTS

SEVERE
Nausea, vomiting, coma, seizures, tachycardia, GI bleeding, metabolic acidosis, hypotension, and respiratory failure. Reported deaths have been due to metabolic acidosis and respiratory failure.

MILD/MODERATE
Nausea, vomiting, tachycardia, tachypnea, weakness, lethargy, transient confusion, sore throat or mouth pain, dizziness, transient hypertension, hypokalemia and transient renal insufficiency.

ONSET
Toxic effects generally develop within 2 hours after exposure.

VITAL SIGNS
Tachypnea, hypotension, and irregular pulse.

CARDIOVASCULAR
Circulatory shock and sinus tachycardia.

RESPIRATORY
Respiratory tract irritation, cough, and respiratory failure, non-cardiogenic pulmonary edema, capillary engorgement, and interstitial hemorrhages of the lungs.

NEUROLOGIC
Incoordination, vertigo, confusion, paresthesias, spastic contracture of the hands, seizures, cerebral edema, giddiness, headache, CNS depression, weak or absent reflexes, paralysis, and mental disturbances.

GASTROINTESTINAL
Nausea and vomiting.

HEPATIC
Liver glutathione depletion, inactivation of drug-metabolizing enzymes, hemorrhage, liver damage, and hepatic necrosis.

ACID-BASE
Metabolic acidosis.

PATIENT DISPOSITION

All symptomatic patients should be admitted to the hospital.
Symptoms may occur within 3 hours of exposure. Symptomatic patients should be monitored for at least 48 hours for level of consciousness, respirations, seizures, and BP.

ORAL/PARENTERAL EXPOSURE

Do NOT induce emesis

GASTRIC LAVAGE
Consider after ingestion of a potentially life-threatening amount of poison if it can be performed soon after ingestion (generally within 1 hour).

ACTIVATED CHARCOAL

SEIZURES
Administer a benzodiazepine IV.
Consider phenobarbital or propofol if seizures recur after diazepam 30 mg (adults) or 10 mg (children > 5 years).
Monitor for hypotension, dysrhythmias, respiratory depression, and need for endotracheal intubation. Evaluate for hypoglycemia, electrolyte disturbances, hypoxia.

ACUTE LUNG INJURY
Maintain ventilation and oxygenation and evaluate with frequent ABG or pulse oximetry monitoring.

HYPOTENSION
Infuse 10 to 20 mL/kg isotonic fluid. If hypotension persists, administer dopamine or norepinephrine

EXPERIMENTAL THERAPY

ETHANOL THERAPY

Ethanol (ETOH) partially inhibits the formation of toxic metabolites.

LOADING DOSE:
Administer 10 mL/kg of 10% ETOH in D5W over 30 minutes.

MAINTENANCE DOSE
Administer 1 to 2 mL/kg/hr of 10% ETOH in D5W by IV infusion. Aim at achieving and maintaining 100 to 130 mg/mL blood ethanol levels.

N-ACETYLCYSTEINE (NAC)

N-Acetylcysteine (NAC) may be helpful to promote resynthesis of glutathione in liver cells and increase conjugation and detoxification.

ORAL NAC DOSING
loading dose of 140 mg/kg followed by 70 mg/kg administered every 4 hours.

IV NAC DOSING
150 mg/kg NAC in 200 ml of D5W administered over 15 minutes followed by 50 mg/kg in 500 ml D5W over the next 4 hours. Finally, 100 mg/kg NAC in 1000 ml D5W over the next 16 hours. 

Reference: 

POISINDEX® Managements 
Last Modified: May 13, 2011

Acute Radiation Syndrome

Acute Radiation Syndrome from Sun YaiCheng

Units of Radiation

Exposure
Conventional unit: Roentgen

Absorbed dose
Conventional unit: rad
International system of unit: Gray
1 Gy = 100 rad

Dose equivalent
Conventional unit: Roentgen equivalents man (rem)
International system of unit: Sievert
1 Sv = 100 rem

Acute Radiation Syndrome

Stage I: Prodromal stage (chiefly gastrointestinal)

• Onset: minutes to hours (ARS is fatal if GI symptoms develop within 2-4 hrs)
• Duration: 48-72 hrs 
• Presentation: nausea, vomiting; also diarrhea, cramps

Stage II: Latent stage (chiefly hematopoietic)

• Onset: hours to days
• Duration: 1.5-2 wks
• Presentation: asymptomatic → bone marrow supression

Stage III: Manifest stage (multisystem involvement)

• Onset: 3-5 wks
• Duration: variable

• Presentation:

CNS/CVS (>15 Sv)
Cardiorespiratory/GI system (>5 Sv)
Reticuloendothelial system (>1 Sv) 

Stage IV: Recovery or Death

• Onset: weeks
• Duration: weeks to months
• Presentation: leading cause of death before recovery is sepsis

Prognosis According to the Lymphocyte Count within the First 48 Hours after Acute Exposure to Penetrating Whole-Body Radiation

MINIMAL LYMPHOCYTE COUNT PER MM2	APPROXIMATE ABSORBED DOSE (GY)	EXTENT OF INJURY	PROGNOSIS
1400–3000 (normal range)	0–0.4	No clinically significant injury	Excellent
1000–1499	0.5–1.9	Clinically significant but probably nonlethal	Good
500–999	2–3.9	Severe	Fair
100–499	4–7.9	Very severe	Poor
<100	≥8	Most severe	High incidence of death even with hematopoietic stimulation

Commonly Treated Forms of Internal Contamination

Radionuclide	Treatment	Mechanism of Action	Usual Administration
Iodine	Potassium iodide	Blocks thyroid uptake	130 milligrams PO for adults
Plutonium	Ca-DTPA or Zn-DTPA	Chelation	1 gram in 250 mL NS or 5% dextrose in water over 60 min
Tritium	Water	Dilution	Oral: 3–4 L a day for 2 wk
Cesium	Prussian blue	Decrease GI uptake	1 gram in 100–200 mL water three times a day for several days
Uranium	Bicarbonate	Alkalinization of urine	2 ampules in 1 L NS at 125 mL/h

Top 10 Key Points For Medical Management of Radiation Casualties

1. Patients should be medically stabilized from their traumatic injuries before radiation injuries are considered, then evaluated for either external radiation exposure or radioactive contamination.
2. An external radiation exposure outside the person does not make the person radioactive. Even such lethally exposed patients are no hazard to medical staff.
3. Nausea, vomiting, diarrhea, and skin erythema within 4 hours may indicate very high external radiation exposures. Such patients will show obvious lymphopenia in 8 to 24 hours. Evaluate with serial CBCs. 
4. Radioactive material may have been deposited on or in the person (contamination). More than 90% of surface radioactive contamination may be removed by removal of the clothing. Most remaining contamination on exposed skin is effectively removed with soap, warm water, and a washcloth. 
5. Protect yourself from radioactive contamination by observing standard precautions, including protective clothing, gloves, and a mask.
6. Radioactive contamination in wound or burns should be handled as if it were simple dirt.
7. In a terrorist incident, there may be continuing exposure of the public that is essential to evaluate. Initially suggest sheltering and a change of clothing or showering. Administration of potassium iodide is indicated only when there has been a confirmed release of radioiodine.
8. When there is any type of radiation incident, many persons will want to know whether they have been exposed or are contaminated. Provision needs to be made to potentially screen thousands of such persons.
9. Clinically significant acute radiation syndrome seldom if ever occurs in people receiving less than 1 Gy of whole-body radiation.
10. The principles of time/distance/shielding are key. Radiation dose is diminished by reducing time spent in the radiation area (moderately effective), increasing distance from a radiation source (very effective), or using metal or concrete shielding (less practical).

Reference

Radiation Injuries. Tintinalli's Emergency Medicine: A Comprehensive Study Guide, 2011, pp 56-61

Disaster Management and Emergency Preparedness. Advanced Trauma Life Support, 2008, pp 333-334

Medical Treatment of Radiological Casualties: Current Concepts. Ann Emerg Med. 2005;45:643-652

Serotonin Syndrome

Serotonin Syndrome from Sun YaiCheng

The Serotonin Syndrome
N Engl J Med 2005;352:1112-20.

Clinical triad of the serotonin syndrome:

1. Mental-status changes
   

   agitation and delirium

2. Autonomic hyperactivity
   

   tachycardia, mydriasis, diaphoresis, the presence of bowel sounds and diarrhea

3. Neuromuscular abnormalities
   

   Hyperreflexia, inducible clonus, myoclonus, ocular clonus, spontaneous clonus, peripheral hypertonicity, and shivering

Diagnosis

• The presence of tremor, clonus, or akathisia without additional EPS should consider the diagnosis. 

• Physical examination should include a focused assessment of DTR, clonus, and muscle rigidity, in addition to an evaluation of the size and reactivity of the pupils, the dryness of the oral mucosa, the intensity of bowel sounds, skin color, and the presence or absence of diaphoresis.

Hunter Serotonin Toxicity Criteria
QJM 2003;96:635-42

Differential Diagnosis

Condition	Serotonin syndrome	Anticholinergic “toxidrome”	NMS	Malignant hyperthermia
Medication History	Proserotonergic drug	Anticholinergic agent	Dopamine antagonist	Inhalational anesthesia
Onset	<12 hr	<12 hr	1–3 days	30 min to 24 hr
Vital Signs	Hypertension, tachycardia, tachypnea, Hyperthermia (>41.1°C)	Hypertension (mild), tachycardia, tachypnea, hyperthermia (typically < 38.8°C)	Hypertension, tachycardia, tachypnea, hyperthermia (>41.1°C)	Hypertension, tachycardia, tachypnea, hyperthermia (can be as high as (46.0°C)
Pupils	Mydriasis	Mydriasis	Normal	Normal
Mucosa	Sialorrhea	Dry	Sialorrhea	Normal
Skin	Diaphoresis	Erythema, hot and dry	Pallor, diaphoresis	Mottled, diaphoresis
Bowel Sounds	Hyperactive	Decreased or absent	Normal or decreased	Decreased
Neuromuscular Tone	Increased, predominantly in lower extremities	Normal	“Lead-pipe” rigidity present in all muscle groups	Rigor mortis–like rigidity
Reflexes	Hyperreflexia, clonus	Normal	Bradyreflexia	Hyporeflexia
Mental Status	Agitation, coma	Agitated delirium	Stupor, alert Mutism, coma	Agitation

Management

1. Removal of the precipitating drugs 

2. Provision of supportive care 

3. Control of agitation

Control of agitation with benzodiazepines is essential in the management of the serotonin syndrome, regardless of its severity. 

Physical restraints are ill-advised and may contribute to mortality by enforcing isometric muscle contractions that are associated with severe lactic acidosis and hyperthermia.

4. Administration of 5-HT2a antagonists

Cyproheptadine

Initial dose: po 12 mg and then 2 mg q2h if symptoms continue
Maintenance dose: po 8 mg q6h

Olanzapine, sublingual 10 mg

Chlorpromazine, intramuscular 50-100 mg

5. Control of autonomic instability

Hypotension should be treated with low doses of direct-acting sympathomimetic amines (e.g., norepinephrine, phenylephrine, and epinephrine).

Hypertension and tachycardia should be treated with short-acting agents such as nitroprusside and esmolol.

6. Control of hyperthermia

In severely ill patients with hyperthermia (temperature >41.1°C), immediate paralysis should be induced with non-depolarizing agents such as vecuronium, followed by orotracheal intubation and ventilation.

There is no role for antipyretic agents in the management of the serotonin syndrome.

相關文章：SSRI & Serotonin Syndrome (中文 prezi 版)

Carbon Monoxide Poisoning

Carbon Monoxide Poisoning from Sun YaiCheng

Carbon Monoxide Poisoning
N Engl J Med 2009;360:1217-25.

Short-Term Management

• Non-rebreather reservoir face mask supplied with high-flow O2, or 100% O2.
• It should be provided until the CO-Hb <5%.

Evaluation

• Neurologic examination
• Exposure history (duration, source, and whether others were exposed)
• ABG, CO-Hb (CO-Hb >3% in nonsmokers or >10% in smokers confirms exposure to CO)
• ECG and cardiac enzymes
• Intentional poisoning: alcohol, BZD, narcotics, amphetamines...

Guidelines

The Undersea and Hyperbaric Medical Society recommends HBO therapy for patients with serious CO poisoning (transient or prolonged unconsciousness, abnormal neurologic signs, cardiovascular dysfunction, or severe acidosis) or patients who are >36 years of age, were exposed >24 hours (including intermittent exposures), or have a CO-Hb level >25%.

A Clinical Policies Subcommittee of the American College of Emergency Physicians states that hyperbaric oxygen "is a therapeutic option for CO poisoned patients; however, its use cannot be mandated....

Conclusions and Recommendations

• Patients who have had CO poisoning should be treated immediately with normobaric oxygen (with a fraction of inspired oxygen as high as possible).
• Clinicians evaluating patients with acute poisoning should consider HBO therapy.
• Patients should be informed that they may not fully recover after poisoning, and they should be given referrals as appropriate for their sequelae.
• Patients should be informed that they may not fully recover after poisoning.
• In one randomized trial, 46% of poisoned patients treated with normobaric oxygen had cognitive sequelae 6 weeks after poisoning, and 45% had affective sequelae.

相關文章： 一氧化碳中毒  (中文版)

Acetylcysteine for Acetaminophen Poisoning

Acetaminophen Poisoning

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Acetylcysteine for Acetaminophen Poisoning

N Engl J Med. July 17, 2008;359:285-92

4 Stages of Acetaminophen Poisoning 

1. Preclinical toxic effects (normal ALT) 
2. Hepatic injury (elevated ALT) 
3. Hepatic failure (hepatic injury with hepatic encephalopathy) 
4. Recovery

Clinical Use

It is prudent to administer acetylcysteine to any patient with an elevated ALT and a history of ingesting more than 4 g of acetaminophen per day.

The Rumack–Matthew Nomogram

Dosing of N-Acetylcysteine 

FDA-approved protocols for treatment of acute acetaminophen ingestion:

• Oral acetylcysteine is loading dose 140 mg/kg, with maintenance doses 70 mg/kg Q4H for 17 doses. 
• IV loading dose is 150 mg/kg over 15 to 60 minutes, followed by infusion 50 mg/kg over 4 hours, and finally infusion 100 mg/kg over 16 hours.

Many toxicologists would recommend repeating the measurements of ALT and acetaminophen concentrations as the patient approaches the end of the 16-hour infusion period and continuing treatment if the ALT is elevated or if the acetaminophen concentration is measurable.

OPD therapy may be considered for patients with a 

• confirmed accidental
• repeated supra-therapeutic ingestion
• supra-therapeutic acetaminophen concentration (threshold of <70 µg /ml)
• low-grade elevation of the ALT (<3 times the upper limit of the reference)

The patient can be discharged with 3 maintenance doses to be taken every 4 hours and be re-evaluated 12 hours after the loading dose. 

Treatment can be discontinued if the patient meets the criteria for stopping therapy (i.e., the ALT is decreasing, and acetaminophen concentration is undetectable).

Patients receiving intravenous acetylcysteine for liver failure should be hospitalized in ICU. Treatment is continued until the hepatic encephalopathy resolves and the ALT and creatinine and INR have substantially improved or until the patient receives a liver transplant.

Side Effects of N-acetylcysteine

• Vomiting is common with oral administration. 
• The most commonly reported adverse effects of intravenous N-acetylcysteine are anaphylactoid reactions (15%), including rash, pruritus, angioedema, bronchospasm, tachycardia, and hypotension.

United Kingdom National Health Service guideline recommends treating patients who have acute acetaminophen overdose and a acetaminophen concentration above the probable-toxicity line (the line that begins at 200 µg/ml at 4 hours after ingestion) and high-risk (alcoholic or malnourished) patients who have a concentration above high-risk line that begins at 100 µg/ml at 4 hours.

American College of Emergency Physicians recommends acetylcysteine therapy for any patient with acute acetaminophen ingestion and a timed serum concentration above the line that begins at 150 µg/ml at 4 hours, as well as for any patient with liver injury or liver failure.

SSRI & Serotonin Syndrome

SSRI on Prezi

 Serotonin Syndrome

Sternbach 診斷標準(1991)： 必備條件加上十項主要條件的三項以上。 必備條件:

• 增加單一神經激胺作用的藥物劑量或加入另一種促進神經激胺作用的藥物。
• 排除其他因藥物疾病或神經精神疾病所導致的異常。

主要條件:

1. 神智改變
2. 躁動                             
3. 動作不協調                  
4. 肌跳躍(myoclonus)    
5. 顫抖                          
6. 震顫
7. 反射增強
8. 流汗
9. 腹瀉
10. 發燒

Hunter Serotonin Toxicity Criteria QJM 2003;96:635-42

一氧化碳中毒

Carbon Monoxide Poisoning from Sun YaiCheng

一氧化碳中毒 (AILS Course)

急性一氧化碳中毒的處置重點：

1. 急性一氧化碳中毒之病患，應立即給予高濃度氧氣治療 (100% O2)
2. 評估急性一氧化碳中毒病患的臨床症狀，以決定是否需高壓氧治療 (HBO)
   
3. 病患出院前須告知神經精神後遺症之風險 (Delayed Neuropsychologic Sequelae)