Abstract
The rate of exposure to analgesics including opioids and sedatives continues to rise each year. Rates of opioid abuse and deaths due to overdose are highest among non-Hispanic whites males, between 20 and 64 years old, from low socioeconomic and rural populations.
Keywords
Opioid Overdose
Epidemiology
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The rate of exposure to analgesics including opioids and sedatives continues to rise each year [1].
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Rates of opioid abuse and deaths due to overdose are highest among non-Hispanic whites males, between 20 and 64 years old, from low socioeconomic and rural populations [2].
History
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Know type of opioid used (if possible), route of exposure, amount taken, time ingested, possible co-ingestion of other substances, and prior history of opioid abuse. If the patient is not able to provide this information, it should be ascertained from family members/friends. Empty prescription bottles will also provide important information.
Serum Half-Life (t 1/2) of Commonly Prescribed Opioids (Table 7.1)
Serum half-life (t 1/2) of the drug ingested is an important factor in the length of duration and dosing of naloxone. Naloxone’s t 1/2 and duration is shorter than most opioids; therefore, overdose of long acting or extended release opioids may require multiple IV boluses of naloxone or continuous infusion (see treatment).
Physical Exam Found in Opioid Overdose
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Vitals: Examine for hypothermia, bradycardia
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Psych: Possible euphoria
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Neuro: Depressed mental status, somnolence, decreased arousal, coma (e.g., especially with Tramadol/Meperidine) [3] can have restlessness, agitation, confusion, jerking, and/or seizures [4]
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HEENT: Miosis
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Cardio: Evaluate for hypovolemia
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Resp: Decreased respiratory rate (remember normal may be 8–12 breaths/min particularly at night), decreased tidal volume
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Pulmonary edema: Rales/hypoxia/frothy sputum seen in patients with overdose of heroin and other opioids [5]
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GI: Decreased bowel sounds
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Skin: Track/needle marks commonly found in the forearms and sometimes in feet
Differential Diagnosis
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Ethanol/Benzo/Clonidine intoxication
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Hypoglycemia
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CVA (altered mental status)
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Pontine hemorrhage (presents with miosis)
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Ketamine overdose (CNS and respiratory depression)
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PCP overdose (CNS depression and miosis)
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Sepsis (hypovolemia/altered mental status)
Workup
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Labs
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Blood glucose level: Rule out hypoglycemia
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UTOX: Rule out ingestion of another toxic substance and know what substance they ingested
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CBC, Blood Cx, UA, rule out infection
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ABG: Assess respiratory status
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BMP: Detect electrolyte abnormalities
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EKG: Methadone causes QTc prolongation/Torsades de Pointes [6]
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Imaging
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CXR: Reserved for patient with hypoxia or abnormal lung sounds. May reveal opioid-induced pulmonary edema.
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CT Head without contrast: Rule out CVA/mass effect/herniation
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Treatment
If no respiratory depression and patient is arousable, with holding opioid along with IVF hydration and monitored vital signs may be adequate
In Severe Cases Consider
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Naloxone: μ-opioid receptor competitive antagonist
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Pharmacology:
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Onset: IV: 2–3 min
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Duration: 10–15 min as it quickly redistributes in adipose tissues [4]
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Half-life: 45–100 min
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*The effective dosing and length of naloxone administration will depend on the type of ingested opioid and its affinity to the mu receptor, amount of ingested opioid, patient’s weight, and the degree of penetration into CNS. Most of the time this information is unattainable and dosing should be started empirically [7].
IV/IM naloxone is used to maintain adequate ventilation
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If respiratory rate >12 and O 2 Sat >90 on RA → closely monitor the patient’s vital signs. Naloxone can be held, and opioid will be cleared by normal metabolism.
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Significant hypoxemia, significant hypotension, or respiratory rate < 6–8 can treat with naloxone [4].
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Ensure adequate respiration with bag-valve mask prior to naloxone administration. Because of its possible side effects, naloxone use should be avoided if possible and only used when absolutely necessary.
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IV bolus:
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Initial dose of naloxone should be 0.4–1 mg can be diluted with 10 ml saline and 0.1–0.2 mg IV bolus can be given every 1–2 min if required [4]. If patient respiratory status (O2 saturation and respiratory rate) does not improve, consider increasing frequency to every 2 min until improvement is seen or a maximum dose of 15 mg is given [7]. Bolus dose increase should only be given if 0.1–0.2 mg is not effective after multiple doses to avoid side effects of naloxone [4].
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If no improvement is seen after a few doses, especially after 15 mg total it is unlikely that the underlying etiology is opioid overdose. A total of 15 mg should be avoided if necessary as naloxone can cause serious complications.
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If patient continues to have recurrent respiratory depression after IV bolus, then IV continuous infusion of naloxone should be considered.
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IV continuous infusion:
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If patient overdosed on long acting or extended release opioid (i.e., Methadone, fentanyl patch), patient should be monitored in ICU setting and started on continuous naloxone infusion. Orotracheal intubation can be an alternate option especially if patient is found to have pulmonary edema [7].
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Initial bolus dose of IV naloxone is given followed by continuous infusion of naloxone 4 mg diluted in 1 L of 0.45 % saline. The rate of infusion can be started at 100 cm3/h (0.4 mg/h). The infusion rate, length of duration, and concentration can be adjusted depending on the resolution of patient’s clinical symptoms [8]. Stop infusion when patient’s saturation has improved or if patient is having acute withdrawal symptoms. Observe for another 4–6 h.
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Stop naloxone administration if signs of opioid withdrawal are seen (see below)
Goal of treatment with naloxone → maintain adequate ventilation
Caution: Naloxone Use/Overdose Can Cause
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Acute pain crisis [4]
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Acute withdrawal symptoms: Seizures, cardiac arrhythmias, severe hypertension, nausea, vomiting, piloerection, diarrhea, yawning, lacrimation, rhinorrhea
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Severe abdominal pain, psychosis, myocardial infarction [4]
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Pulmonary edema: Most likely due to increased afterload secondary to catecholamine surge in the setting of iatrogenic reversal (naloxone) of opioid toxicity. This can cause interstitial edema [5, 9].
Opioid Withdrawal
Etiology
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Natural: Chronic users of opioids develop physical dependence and are predisposed to withdrawal once they stop taking the drug, run out of medications or rapidly decrease their dose
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Iatrogenic: High-dose or rapidly infused naloxone administered to a patient who is overdosed with an opioid may precipitate excess catecholamine release and consequently pulmonary edema and cardiac arrhythmias
HistoryMost patients experiencing withdrawal symptoms will have been on the opiates for at least several weeks but this can start earlier. Withdrawal symptoms can begin even with slight decreases in opioid doses in some patients [4]. Symptoms may present 6–12 h after last dose of short-acting opioid and 24–48 h after last methadone dose. Common symptoms/complaints are listed in Table 7.2.
Physical Exam
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Vitals: Tachycardia/arrhythmias (rare), hypertension, tachypneic
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GI: Hyperactive bowel sounds
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Neuro/Psych: Agitated, anxiousness, tremors
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HEENT: Mydriasis, lacrimation, rhinorrhea
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Skin: Piloerection, diaphoretic
Differential Diagnosis
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Ethanol/Benzo withdrawal
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Sympathomimetic intoxication
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Cholinergic agent toxicity
Treatment
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Opioid withdrawal is usually not life threatening but patients especially those with comorbidities can be placed at heightened risk of increased intracranial pressure and unstable angina due to the sympathetic tone [4]
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Even to healthy patients, opioid withdrawal is very uncomfortable to experience [4]
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Outpatient management may be sufficient for most withdrawal symptoms
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In severe case—Continuous monitoring of vital signs and possible telemetry
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If patient is hypovolemic due to excessive vomiting/diarrhea, treat with IVF, and consider inpatient treatment
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If withdrawal accompanied by serious cardiopulmonary disease (i.e., cardiac arrhythmias, hypertension, pulmonary edema) or suicidal ideation or psychotic symptoms, then patient should be monitored in acute setting [10].
Opioid agonist therapy (not given in cases of iatrogenic produced withdrawal, should be treated by a trained specialist)
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Restart opiates in patients where this is appropriate, can consider IV or IM dose in severe cases
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Opiate taper can be initiated if goal is for patient to be off the opiates
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For example: If a patient is chronically on Percocet 10/325 five times a day, instead of just stopping this medications abruptly, you can decrease the dose by 5–10 mg each week as tolerated
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Opiate tapers are usually only given to compliant patients who are not at risk of suicide attempt, not using concurrent illicit substances, and not getting opiates from other doctors
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Other options to consider:
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Switch to long half-life pure opioid agonist such as methadone, sustained release morphine or oxycodone, and transdermal fentanyl patches [4]
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Methadone (can be dosed once daily): Long-acting synthetic opioid agonist; taper dose weekly by 3 % of the initial dose
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Use of partial agonist/antagonist opioids: Buprenorphine (4–16 mg PO daily) is another option. Taper over several weeks [10].
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Non-opioid Adjunctive Medications
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Clonidine shown to reduce opioid withdrawal symptoms [11] (caution of hypotension)
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0.1–0.2 mg every 4 h prn, taper after day 3 with total treatment lasting about 10 days [10].
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*Acute withdrawal symptoms due to naloxone treatment should be managed symptomatically. Naloxone should be stopped immediately if withdrawal symptoms are seen.
Symptomatic Treatment
Symptomatic treatment may not be necessary for mild symptoms in patients who will be restarted on opiates (Table 7.3)
Benzodiazepine Withdrawal
Many features of benzo withdrawal are similar to that of opioid withdrawal. Some signs of benzo withdrawal include hyperarousal, tremors, seizures, delirium, delusions, hallucinations, nausea, vomiting, tachycardia, and diaphoresis. Unlike opioid withdrawal, benzo withdrawal can be very dangerous, life threatening, and can cause seizures; these patients should be sent to an expert or managed in an inpatient setting [4].
Abbreviations
- ABG:
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Arterial blood gases
- BMP:
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Basic metabolic panel
- CBC:
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Complete blood count
- CNS:
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Central nervous system
- CVA:
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Cerebrovascular accident
- CXR:
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Chest X-ray
- Cx:
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Culture
- EKG:
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Electrocardiogram
- GI:
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Gastrointestinal
- HEENT:
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Head, eyes, ears, neck, throat
- IM:
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Intramuscular
- IV:
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Intravenous
- O2 :
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Oxygen
- PCP:
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Phencyclidine
- prn:
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As needed
- UA:
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Urinalysis
- UTOX:
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Urine toxicology
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Paul, G. (2015). Opioid Overdose and Withdrawal. In: Sackheim, K. (eds) Pain Management and Palliative Care. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2462-2_7
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