1) An epidemic of heroin adulterated with scopolamine resulting in severe anticholinergic toxicity was reported (Hamilton et al, 2000).
2) A case of amphetamine toxicity caused by use of adulterated heroin has been reported (Choudry & Doe, 1986).
3) Clenbuterol has also been found as an adulterant in heroin (Hieger et al, 2015; U.S. Drug Enforcement Administration, 2009).

a) Fever in a patient with a history of injection drug use should be presumed to be secondary to infection until proven otherwise.

a) Hypothermia has been reported in the setting of opioid overdose secondary to attempts by bystanders to revive patients by immersion in ice water (Osterhoudt & Perrone, 2002).

a) INCIDENCE: In a retrospective study of 726 patients, 94% of opioid overdose patients had pinpoint pupils (Sporer et al, 1996).

a) CHRONIC ABUSE: Rapidly developing profound bilateral sensorineural hearing loss, developing over several weeks, has occurred following chronic abuse of high dose acetaminophen with opioids. In 2 patients, vestibular function appeared to be spared, despite profound hearing loss. Audiometric testing suggested that the sensory end organ was the site of damage. Cochlear implantation was required in one patient to restore functional hearing (Oh et al, 2000).
b) HEROIN: A 27-year-old man with a history of hepatitis C virus infection and heroin abuse in abstinence for 3 years, presented with coma, depressed respiration, increased pulse rate, contracted pupils and vomiting after drinking 4 bottles of vodka and sniffing heroin. He also had hypoxia and hypercapnia, requiring oxygen administration. Following supportive care, including antibiotics for aspiration pneumonia, he regained consciousness 16 hours later and complained of sudden hearing loss on both ears. Standard pure-tone audiometry revealed symmetrical moderate bilateral sensorineural hearing loss. Both otoacoustic emissions and auditory brainstem response waves were absent, indicating both cochlear and retrocochlear involvement. All other physical, neurological and laboratory tests were normal. Following treatment with prednisolone (for 15 days) and magnesium (for 30 days), his symptoms gradually improved. On one month follow-up, audiometry, auditory brainstem responses and otoacoustic emissions were normal (Antonopoulos et al, 2012).
c) HEROIN: A 29-year-old woman with a history of heroin and cocaine abuse, presented with bilateral hearing loss and severe tinnitus after a heroin overdose. On presentation, she was agitated and distractible. She was treated with a course of prednisone and fitted with hearing aids. Her hearing loss gradually improved (Nair et al, 2010).
d) COMBINATION EXPOSURE: An 18-year-old woman developed moderately severe bilateral sensorineural hearing loss after abusing heroin, benzodiazepine, alcohol, and crack (smoked cocaine) for 2 days. Following supportive therapy, including high-dose prednisone for a month and pentoxifylline for 10 months, her hearing sensitivity gradually improved, except for residual high-frequency sensorineural hearing loss (Schweitzer et al, 2011).
e) MT-45 (DESIGNER OPIOID): An observational case series was conducted, involving 9 patients identified with a psychoactive substance intoxication, later identified as MT-45, a designer opioid, as either the sole drug or in combination with other agents (eg, alcohol, phencyclidine, oxycodone, benzodiazepines). Impaired hearing was one of the reported symptoms (Helander et al, 2014).

a) Hypotension from opioids may be due to opioid-induced arteriolar and venous dilation (Nelson, 1998).

a) Hypotension and shock may occur, especially in the presence of prolonged and severe hypoxia (Miller, 1980; Whipple et al, 1994; Lawrenson et al, 1993).
b) Hypotension and a decrease in mental status has occurred following overdose (Whipple et al, 1994). Severe hypotension (70/40 mmHg) and ventricular fibrillation has been reported at 12 hours following a mixed intravenous overdose of cocaine and heroin (McCann et al, 2002).
c) EPIDURAL: Accidental high thoracic epidural doses of sufentanil and bupivacaine resulted in severe hypotension and increased sensory and motor blockade (Wolff et al, 1992).
d) CASE REPORT: Profound circulatory shock was reported in a 17-year-old girl several hours following an intravenous heroin overdose. Systolic central venous pressure of 21 mmHg was recorded with heart rate of 156 beats per minute. Severe depression of myocardial contractility was noted. Volume loading and high dose dobutamine successfully reversed the shock, and recovery was then uneventful (Remskar et al, 1998).

a) Atrial fibrillation has been reported following abuse of crude heroin in an adult man (Lawrenson et al, 1993)

a) VENTRICULAR DYSRHYTHMIAS

a) Bradycardia may be seen and is due to an associated reduction in central nervous system stimulation (Nelson, 1998).

a) Bradycardia may develop in patients with severe respiratory depression (Prod Info AVINZA(R) extended-release oral capsules, 2005).
b) INCIDENCE: Only 2% of 726 patients presented with bradycardia following opioid overdoses as reported in a retrospective study of opioid overdoses in an urban setting (Sporer et al, 1996).

a) Tachycardia (heart rate, 156 beats per minute) and ECG readings of sinus tachycardia and nonspecific ST-T segment changes were reported in a previously healthy 17-year-old girl following an IV heroin overdose (Remskar et al, 1998).

a) Myocardial damage, with focal lesions formed by small mononuclear inflammatory cells and with degenerated, necrotic myocardial fibers and congestion, has been shown to occur as a result of prolonged hypoxic coma following opiate intoxication (Melandri et al, 1996).

a) SUMMARY
b) SPECIFIC AGENTS

a) Acute lung injury (pulmonary edema) may occur after severe opioid overdose (Glassroth et al, 1987; Jaffe & Martin, 1990; Dettmeyer et al, 2000; Warner-Smith et al, 2001; Sporer & Dorn, 2001) and may be a contributing factor in fatal overdoses.
b) INCIDENCE: In a retrospective study of 125 patients admitted to an urban ED with heroin overdose, 13 (10.4%) developed acute lung injury. Patients who developed acute lung injury had a lower respiratory rate on paramedic arrival, and had a shorter duration of heroin use than patients who did not develop acute lung injury. All patients who developed acute lung injury received naloxone in the prehospital setting (Sterrett et al, 2003).
c) BUTYRFENTANYL: CASE REPORT: An 18-year-old man with a past medical history of IV heroin abuse, developed hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage, after snorting an unknown amount of butyrfentanyl instead of acetyl fentanyl. Initially, he was found unconscious by his mother. His mental status improved after receiving 0.4 mg IV naloxone; however, he developed dyspnea and hemoptysis. A chest radiograph revealed bilateral "batwing"-shaped perihilar predominant airspace opacities with diffuse increased interstitial markings. Fentanyl and opiates immunoassays were both positive, but fentanyl was not present in high-performance liquid chromatography and mass spectrometry. Butyrfentanyl was detected using a high-performance gas chromatography obtained from the Bureau of Criminal Apprehension. At this time, his condition deteriorated, requiring intubation. Results from the cytology of the fluid from bronchoalveolar lavage obtained during bronchoscopy were consistent with diffuse alveolar hemorrhage. Echocardiography showed an ejection fraction of 55% to 60% with no wall-motion abnormalities. He was treated with fentanyl, midazolam, and dexmedetomidine to maintain adequate sedation. Following further supportive care, his condition improved gradually and he was extubated on day 4 and discharged 3 days later after receiving treatment for ventilator-associated pneumonia (Cole et al, 2015).
d) HEROIN: Non-cardiogenic pulmonary edema ("heroin-lung") is an infrequent, but severe, complication of heroin overdose and is generally abrupt in onset (immediate-2 hours) following intravenous heroin overdose (Duberstein & Kaufman, 1971). Delayed onset has been described 4 hours following intranasal heroin use (Steinberg & Karlinger, 1968) and 3, 9, 14 and 24 hours following oral methadone ingestions (Wilen et al, 1975; Sey et al, 1971).
e) CASE REPORT (HEROIN): An man presented with acute lung injury following an opiate overdose from smoking crude heroin. Pulmonary arterial wedge pressure was 12 mmHg with a cardiac output of 6.8 L/min (Lawrenson et al, 1993).
f) CASE REPORT (HEROIN): Symmetric alveolar pulmonary edema was shown on chest x-ray in a 17-year-old girl several hours after an intravenous heroin overdose (Remskar et al, 1998).
g) CASE REPORT (PAREGORIC): A 3-week-old infant who received 4 drops 6 times a day of paregoric developed pulmonary edema. With normal recovery, the majority of x-ray changes resolved within 24 to 48 hours (Rice, 1984).

a) BUTYRFENTANYL: CASE REPORT: An 18-year-old man with a past medical history of IV heroin abuse, developed hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage, after snorting an unknown amount of butyrfentanyl instead of acetyl fentanyl. Initially, he was found unconscious by his mother. His mental status improved after receiving 0.4 mg IV naloxone; however, he developed dyspnea and hemoptysis. A chest radiograph revealed bilateral "batwing"-shaped perihilar predominant airspace opacities with diffuse increased interstitial markings. Fentanyl and opiates immunoassays were both positive, but fentanyl was not present in high-performance liquid chromatography and mass spectrometry. Butyrfentanyl was detected using a high-performance gas chromatography obtained from the Bureau of Criminal Apprehension. At this time, his condition deteriorated, requiring intubation. Results from the cytology of the fluid from bronchoalveolar lavage obtained during bronchoscopy were consistent with diffuse alveolar hemorrhage. Echocardiography showed an ejection fraction of 55% to 60% with no wall-motion abnormalities. He was treated with fentanyl, midazolam, and dexmedetomidine to maintain adequate sedation. Following further supportive care, his condition improved gradually and he was extubated on day 4 and discharged 3 days later after receiving treatment for ventilator-associated pneumonia (Cole et al, 2015).

a) Persistence of abnormalities beyond 24 to 48 hours including atelectasis, fibrosis, bronchiectasis, granulomatous disease, and pneumomediastinum suggest the presence of aspiration or bacterial pneumonitis (Saba et al, 1974; Wilen et al, 1975; Glassroth et al, 1987). A frequent autopsy finding in heroin fatalities is undiagnosed pneumonia (Warner-Smith et al, 2001).

a) BULLOUS PULMONARY DAMAGE: Bullous pulmonary damage was found in 2 percent of a group of 387 illicit intravenous drug users. The drugs used by these patients were not specified (Goldstein et al, 1986).

a) Airway obstruction and bronchospasm, or status asthmaticus, have been associated with inhalation of heated heroin. Eosinophils have been detected in the peripheral blood and/or respiratory secretions in these patients. More investigation is needed to determine the factors and the mechanisms involved (Del Los Santos-Sastre et al, 1986; Cygan et al, 2000).
b) HEROIN

a) A marked increase in cerebral deoxygenated hemoglobin following heroin IV injections in 7 heroin-dependent patients was reported (Hock et al, 2002).

a) Acute overdosage of any of the opioid drugs may result in coma, pulmonary edema and cessation of respiration, depending on the dose and degree of tolerance. Prolonged coma may result due to delayed gastric emptying (Melandri et al, 1996a). .
b) INCIDENCE: 64% of 52 patients in a case series of acute opiate overdoses admitted to an ED were reported to have a rating of <8 on the Glasgow Coma Scale (Cook et al, 1998).
c) REMIFENTANIL: A primiparous woman who had received epidural fentanyl with bupivacaine (three 10-mL dose of bupivacaine 0.1% with fentanyl 2 mcg/mL) for labor pain, became unconscious and developed respiratory arrest within 5 minutes of self-administering the first dose of remifentanil (programmed regimen: 40 mcg/mL, 1-mL bolus [40 mcg], 2-min lockout) patient-controlled analgesia (PCA). She recovered within 30 to 60 seconds of supportive care. The PCA machine was examined and it was determined that 160 mcg was inadvertently delivered over 4 attempts (Pruefer & Bewlay, 2012).
d) CASE REPORT: A 25-year-old woman with a 2-year history of heroin inhalation was found comatose in her car. On presentation to the ED, she had a Glasgow Coma Scale score (GCS) of 6, a heart rate of 109 beats/min, and a blood pressure of 168/44 mmHg. Neuroimaging studies revealed hydrocephalus with enlarged ventricles, communicating ventriculomegaly, and cerebellar enhancement. All laboratory results, serial CT scans, and a second MRI were normal. Her cerebellar radiologic changes were improved after an external ventricular drain (EVD) was placed; however, she developed tremor and cogwheeling. She received acetazolamide 500 mg every 12 hours and dexamethasone to treat hydrocephalus. During multiple EVD clamping trials, her intracranial pressures increased and she became obtunded. On day 13 of hospitalization, she received a ventriculoperitoneal shunt (VPS) and she was discharged to a rehabilitation facility with a GCS of 15. On a 3-month follow-up, her symptoms had improved, but she sustained cognitive deficits with a low-pressure headache. Large improvement and increased pachymeningeal enhancement in postgadolinium T1 sequences were observed in a brain MRI (Bui et al, 2015).

a) Decreased mental status is one of the most prominent symptoms in a narcotic overdose, which may progress to coma (Whipple et al, 1994).
b) CASE REPORT: A 52-year-old woman developed only nausea and mild drowsiness after inadvertently receiving 3 mL (3 mg) of diamorphine intrathecally instead of 0.5% bupivacaine for spinal anesthesia for a total knee replacement surgery. She recovered after 48 hours of observation (Jafar & Chowdhry, 2014).

a) ALFENTANIL: A case of jerking movements progressing to seizures and unconsciousness was reported in a 60-year-old man given 25 mcg/kg alfentanil over 30 seconds (Strong & Matson, 1989).

a) Seizures may occur following overdoses, but are unusual following therapeutic dosing. Seizures may be related to hypoxia (Nelson, 1998). Rarely, use of naloxone to reverse opioid overdose has been reported to provoke seizures (Remskar et al, 1998).

a) Toxic Myelopathy

a) Myoclonic activity has been reported in two patients on high-dose spinal opioid therapy for pain (Parkinson et al, 1990).

a) A man developed leukoencephalopathy after heroin overdose presented with axial myoclonus involving the neck flexors, pectoral muscles and abdominal musculature (Hill et al, 2000).

a) MT-45 (DESIGNER OPIOID): An observational case series was conducted, involving 9 patients identified with a psychoactive substance intoxication, later identified as MT-45, a designer opioid, as either the sole drug or in combination with other agents (eg, alcohol, phencyclidine, oxycodone, benzodiazepines). Reported symptoms included paresthesia in the extremities, severe CNS depression, respiratory depression, cyanosis, miosis, and impaired vision and hearing. Routes of administration included oral, IV, nasal, and rectal. Naloxone was administered to 7 of the 9 patients, with 4 of the patients responding well to the treatment (Helander et al, 2014).

a) Stroke may occur as an infrequent complication of heroin abuse (Vila & Chamorro, 1997).
b) CASE REPORT: Ballistic movements after IV heroin overdose were reported in 2 adult patients. In one patient, an MRI revealed bilateral ischemic lesions of the globus pallidus, indicating generalized cerebral hypoxia during a comatose state. The second patient, with an acute left hemiballismus, had an MRI which showed an ischemic infarct in the right striatum. This patient was suspected to have an embolic stroke (Vila & Chamorro, 1997).
c) CASE REPORT: A 28-year-old woman presented with altered mental status after using heroin. Physical examination revealed negative clonus, pinpoint and sluggish pupils, disorientation, persistent confusion, and expressive aphasia. A computed tomographic scan of the head revealed a large 5.1 x 5-cm intraparenchymal hemorrhage in the left frontal lobe, vasogenic edema, and a 5-mm midline shift. Surgical intervention was not considered because of the stable appearance of a repeat imaging. Despite a mild improvement in her cognitive function, she continued to be confused with significant memory loss during her hospitalization. She was discharged to a long-term facility with a diagnosis of hemorrhagic stroke secondary to heroin abuse after other etiologies were ruled-out (Kumar et al, 2015).

a) Heroin-induced spongiform leukoencephalopathy, a result of fluid accumulation within the myelin sheaths, has been reported following heroin intoxication, primarily after inhaling the pyrolysate generated by heating heroin base on aluminum foil ("chasing the dragon").
b) In the initial stage of illness patients demonstrate soft speech, cerebellar ataxia, restlessness and apathy. During the intermediate stage pseudobulbar reflexes, spastic paresis, tremors, myoclonic jerking, hyperreflexia, worsening gait disturbances and choreoathetoid movements may develop. In the terminal stages central fevers, stretching spasms, hypotonia, areflexia and akinetic mutism may develop followed by brain death (Wolters et al, 1982). Progression occurs over weeks or months and not all patients progress through all stages. Mortality is approximately 25%.
c) MRI is the diagnostic modality of choice. Diffusion-weighted (DW) magnetic resonance imaging (MRI) findings may show restriction of water diffusion in white matter at the intermediate stage of disease (Chen et al, 2000). A characteristic pattern may be seen on MRI (Kriegstein et al, 1997) consisting of spongiform demyelination as the morphological substrate of lesions which are hyperintense on T2-weighted MRI and hypodense on CT (Weber et al, 1998).
d) Blood and CSF are typically normal, and cranial CT may be normal early in the course of illness (Long et al, 2003).
e) Autopsy findings include spongiform degeneration of white matter, vacuolization and fluid accumulation in myelin sheaths (Long et al, 2003).
f) CASE REPORTS

a) MT-45 (DESIGNER OPIOID): An observational case series was conducted, involving 9 patients identified with a psychoactive substance intoxication, later identified as MT-45, a designer opioid, as either the sole drug or in combination with other agents (eg, alcohol, phencyclidine, oxycodone, benzodiazepines). Paresthesia in the extremities was one of the reported symptoms (Helander et al, 2014).

a) Delayed postanoxic encephalopathy with cortical blindness was reported following a heroin overdose in a 43-year-old man. Two weeks following the overdose, a MRI revealed bilateral infarcts in the putamen, caudate and parietal and occipital lobes (McDonald et al, 1995) .
b) Hypoxic encephalopathy was reported in a 17-year-old man who 4 days after hospital admission developed encephalopathy as a result of inhaling an unknown quantity of heroin (Zuckerman et al, 1996).
c) An atypical course following acute heroin intoxication has included encephomyelo-polyradiculoneuropathy with diffuse impairment of the central and peripheral nervous system in one patient (Batora et al, 2002).

a) Acute transverse myelitis has been associated with intravenous or intranasal insufflation of heroin. A period of heroin abstinence followed by a single use of heroin has led to paralysis. Concurrent symptoms have included urinary retention, heroin-associated rhabdomyolysis, and onset of paraplegia after awakening from sleep. Normal CSF findings on routine analysis are reported in most cases, although pleocytosis and increased total protein may occur. MRI findings may, in some cases, be consistent with acute transverse myelitis. Following rehabilitation, patients often recover after several weeks (McCreary et al, 2000).

a) HEROIN

a) CASE REPORT: A 25-year-old woman with a 2-year history of heroin inhalation was found comatose in her car. On presentation to the ED, she had a Glasgow Coma Scale score (GCS) of 6, a heart rate of 109 beats/min, and a blood pressure of 168/44 mmHg. Neuroimaging studies revealed hydrocephalus with enlarged ventricles, communicating ventriculomegaly, and cerebellar enhancement. All laboratory results, serial CT scans, and a second MRI were normal. Her cerebellar radiologic changes were improved after an external ventricular drain (EVD) was placed; however, she developed tremor and cogwheeling. She received acetazolamide 500 mg every 12 hours and dexamethasone to treat hydrocephalus. During multiple EVD clamping trials, her intracranial pressures increased and she became obtunded. On day 13 of hospitalization, she received a ventriculoperitoneal shunt (VPS) and she was discharged to a rehabilitation facility with a GCS of 15. On a 3-month follow-up, her symptoms had improved, but she sustained cognitive deficits with a low-pressure headache. Large improvement and increased pachymeningeal enhancement in postgadolinium T1 sequences were observed in a brain MRI (Bui et al, 2015).
b) CASE REPORT: A 28-year-old man who became unconscious after using heroin inhalation, developed progressive parkinsonism over the next 4 weeks. He also complained about worsening headaches that started a few days before presentation. Physical examination showed sluggish pupils, downward ocular deviation, and intermittent tonic spasms. A brain MRI showed supratentorial symmetric white matter lesions typical of heroin-induced leukoencephalopathy, ventriculomegaly with sulcal effacement and tonsillar herniation. Brainstem compression from cerebellar swelling obliterated the 4th ventricle. He regained consciousness after the placement of ventriculostomy and treatment with dexamethasone; however, his conditioned worsened and despite further supportive care, including mannitol therapy, he died about 2 months after the onset of his illness (Dastur & Chang, 2015).

a) High doses of opioids or combination opioid agonists/antagonists have been reported to cause a paradoxical pain reaction which resolves upon cessation of the drug.

a) Wound botulism, which has been associated with subcutaneous or intramuscular black tar heroin injections, has caused potentially lethal, descending, flaccid paralysis when Clostridium botulinum spores germinated in the wound which released neurotoxins (Passaro et al, 1998).

a) A case of paraplegia below T12, compartment syndrome in one leg and eventual limb amputation was reported in a 29-year-old man with a known history of heroin abuse following a prolonged period of immobility (prolonged 'lotus' posture) as a result of acute heroin overdose (Kumar et al, 1999).

a) Fentanyl, sufentanil, and alfentanil were administered as toxic doses to rats in a study of neurotoxicity. All three drugs produced histologic evidence of limbic system injury (Kofke et al, 1996).

a) DELAYED GASTRIC EMPTYING: Most members of the opioid group tend to delay gastric emptying so that reversal with an opioid antagonist may result in a return of peristalsis and further absorption of drug which results in prolonged coma (Jaffe & Martin, 1990).

a) CASE REPORT: A 52-year-old woman developed only nausea and mild drowsiness after inadvertently receiving 3 mL (3 mg) of diamorphine intrathecally instead of 0.5% bupivacaine for spinal anesthesia for a total knee replacement surgery. She recovered after 48 hours of observation (Jafar & Chowdhry, 2014).

a) Cramping and constipation may occur (Prod Info Infumorph(R), 1993; Prod Info Duragesic(R), 2001).

a) Hyperamylasemia has been reported (Jaffe & Martin, 1990). Theoretically, pancreatitis is a possible adverse effect of opioid overdoses.

a) Acute tubular necrosis secondary to rhabdomyolysis and myoglobinuria have been associated with impure heroin and the complications of seizures associated with opioid overdose (Nicholls et al, 1982; Krige et al, 1983; Chan et al, 1990; Rice et al, 2000; McCann et al, 2002; Kumar et al, 1999).

a) Focal glomerulosclerosis, membranous glomerulonephritis (associated with chronic hepatitis B), and immune complex proliferative glomerulonephritis (associated with endocarditis) have been described with heroin abuse (Cunningham et al, 1983; Dubrow et al, 1985).

a) Heroin-associated nephropathy is a poorly explained cause of end stage renal disease (Cunningham et al, 1983; doSameiroFaria et al, 2003).

a) Renal amyloidosis is associated with long term parenteral heroin abuse (Dubrow et al, 1985; Neugarten et al, 1986).

a) CASE REPORT: A case of priapism, present for 12 hr prior to ED admission, was reported in a 41-year-old man which began 4 hours following a dose of IV heroin. Similar episodes had occurred in the past, all following heroin use. When medical therapy failed, both corpora cavernosa were drained and irrigated with lidocaine-epinephrine solution. Four days later the patient had another episode of heroin-induced priapism requiring surgical intervention (Nocchi & D'az, 1999).

a) Leukocytosis was reported in 90% of 18 hospital admissions in Taiwan due to heroin overdoses (Chan et al, 1995).
b) Extreme leukocytosis (31.0 x 10(9)/L) without leftward shift in a 17-year-old girl was reported after an intravenous heroin overdose (Remskar et al, 1998).

a) Following a mixed intravenous heroin/cocaine overdose, an adult developed disseminated intravascular coagulation and acute renal failure and hyperkalemia subsequent to rhabdomyolysis . The patient died 2 months later with multiorgan failure (McCann et al, 2002).

a) Pruritus is a common adverse event following the administration of opiates, particularly morphine sulfate (Larijani et al, 1996).

a) CASE REPORT/INTRATHECAL: A 33-year-old woman in active labor was inadvertently given 45 mcg of sufentanil (a 9-fold increase; intended does 5 mcg) into the intrathecal space and complained of pruritus within 2 minutes of receiving the dose along with some difficulty swallowing (Coleman et al, 2009). The infant was delivered within 12 minutes of the event and had apgar scores of 8 and 9 at 1 and 5 minutes. The woman received naloxone shortly after delivery for complaints of severe pruritus, which the authors suggested may have limited the development of other adverse events. The patient and infant were discharged the following day.

a) BLACK TAR HEROIN ADULTERATED WITH CINNAMON: A 38-year-old heroin user (500 mg IV twice daily) developed a painful and petechial rash on the palmar aspect of the left forearm soon after injecting (IV) black tar heroin adulterated with cinnamon. She did not experience any euphoria or opioid-like symptoms; however, she developed mild heroin withdrawal symptoms, including myalgia, palpitation, and anxiety. On presentation, she was mildly tachycardic (101 beats/min) and hypertensive (BP 142/86 mmHg). Following supportive care, including warm compresses and NSAIDs, her symptoms resolved (Hendrickson, 2015).

a) CASE REPORT: Diffuse cutaneous scleroderma of the hands, arms and face was reported in a 38-year-old man 3 years after successful detoxification from a 10 year history of IV heroin abuse. Subsequently, multiple telangiectases and painful ulcers of the fingers appeared. Four years earlier, while still using IV heroin, he had begun experiencing Raynaud's phenomenon (Biasi et al, 1998).

a) DESOMORPHINE

a) HEROIN: CASE REPORT: A 57-year-old man developed extravasation injury following heroin injections, and presented with a skin lesion on the posterior region of the left forearm with extensive necrosis of skin and subcutaneous layer, involving the underlying muscle planes. The lesion had a sanious, fibrinous, secreting and smelly bottom. He received ciprofloxacin for 2 weeks after the lesion culture was positive for Pseudomonas aeruginosa. He was treated with daily dressing before the chemical debridement of the lesion using a topical ointment containing a collagenase plus hyaluronic acid (Bionect Start(R)). Each dressing contained 4 phases: disinfection with sodium hypochlorite 0.05% and povidone-iodine solution 10%, cleansing with saline solution, the application of a layer of 2 mm Binect Start(R) and covering with a pre-medicated patch. His symptoms gradually improved and a complete wound healing was observed 3 months after presentation (Onesti et al, 2014).

a) Rhabdomyolysis, myoglobinuria, and subsequent acute tubular necrosis (ATN) have been associated with impure heroin injections, prolonged coma, or as a complication of seizures associated with opioid overdose (Nicholls et al, 1982; Krige et al, 1983; Sporer, 1999; Rice et al, 2000). In a mixed overdose of cocaine and heroin, rhabdomyolysis and hyperkalemia led to cardiac arrest (McCann et al, 2002).
b) INCIDENCE: A 22% (4 of 18 patients) incidence of rhabdomyolysis occurred in heroin overdoses in one case series (Chan et al, 1995a).
c) CASE REPORTS

a) Compartment syndrome may occur in a comatose patient following abuse of narcotic injections, such as heroin (Franc-Law et al, 2000; Sporer, 1999; Kumar et al, 1999).
b) CASE REPORT: A mixed intravenous overdose of cocaine and heroin has resulted in lower limb compartment syndrome requiring fasciotomy (McCann et al, 2002).
c) CASE REPORT: A case of bilateral tibial compartment syndrome, severe hyperkalemia (9.2 mmol/L) and rhabdomyolysis (CPK 226,311 U/L), after abusing an unknown amount of opiates, benzodiazepines and cannabinoids with death resulting, was reported in a 35-year-old man(Ochoa-Gomez et al, 2002).
d) CASE SERIES: The most frequent signs/symptoms in 4 cases of opiate (heroin) induced acute atraumatic compartment syndrome (AACS) were edema, pain, tension, and skin changes. The implicated mechanism of opiate-induced AACS was limb compression due to prolonged comatose state (Crush Syndrome). Prolonged limb compression tended to progress to complications such as cardiac dysrhythmias, hypotension, azotemia and renal failure. Long-term sequelae of motor loss, sensory disruption and development of contracture were reported (Franc-Law et al, 2000).

a) Hypoglycemia has been reported in a young adult man following heroin and amphetamine abuse. The patient presented in a coma and was restored to consciousness with a dextrose infusion. After losing consciousness again, he responded to naloxone (Kao et al, 1994).

a) No teratogenic effects or adverse effects on embryofetal development were observed in animals at doses up to 115 times the human exposure (Prod Info VIBERZI oral tablets, 2015).

a) There was no evidence of teratogenicity or fetal harm when rats were given subQ nalbuphine at doses up to 100 mg/kg/day (approximately 6 times the maximum recommended human dose (MRHD)) and when rabbits were given IV nalbuphine at doses up to 32 mg/kg/day (approximately 4 times the MRHD) (Prod Info nalbuphine hydrochloride subcutaneous injection, IM injection, IV injection, solution, 2007).

a) In animal studies, there were no teratogenic effects observed when pregnant rats (5 mg/kg) and rabbits (0.8 mg/kg) were given remifentanil at doses up to 400 times and 125 times, respectively, the maximum recommended human dose on a mg/m(2) basis. Rats administered remifentanil throughout late gestation and lactation at IV doses up to 5 mg/kg (400 times the maximum recommended human dose on a mg/m2 basis) showed no significant effect (survival, development, or reproductive performance) on the F1 generation (Prod Info ULTIVA(R) IV injection, 2007).

a) In a retrospective serial, cross-sectional analysis that estimated 21,732 infants with NAS and 3,716,916 other hospital births in 2012, reported the following complications in NAS patients compared to other hospital births: low birthweight (24.4% vs 7.2%), transient tachypnea of the newborn (11.7% vs 3.1%), meconium aspiration syndrome (2.8% vs 0.4%), respiratory distress syndrome (4.5% vs 2%), jaundice (32.8% vs 19.1%), feeding difficulty (17.3% vs 3%), seizures (1.4% vs 0.1%) and possible sepsis (14.8% vs 2.2%; p less than 0.001) (Patrick et al, 2015).

1) NALORPHINE (Briggs et al, 1998)

1) ALFENTANIL HYDROCHLORIDE* (Prod Info ALFENTA(R) IV injection, 2008)
2) ALPHAPRODINE* (Briggs et al, 1998)
3) ETHOHEPTAZINE* (Briggs et al, 1998)
4) OPIUM (Prod Info opium tincture (DEODORIZED) oral solution, 2008)
5) OPIUM ALKALOIDS/BELLADONNA EXTRACT (Prod Info Belladonna & Opium rectal suppositories, 2005)
6) PAREGORIC SYRUP (Prod Info paregoric oral solution, 1996)
7) PENTAZOCINE* (Briggs et al, 1998)

a) *Risk Factor D if used for prolonged periods or in high doses at term (Briggs et al, 1998).

1) ANILERIDINE* (Briggs et al, 1998)
2) HEROIN* (Briggs et al, 1998)
3) NALBUPHINE (Prod Info nalbuphine hydrochloride subcutaneous injection, IM injection, IV injection, solution, 2007)

a) *Risk Factor D if used for prolonged periods or in high doses at term (Briggs et al, 1998).

a) No adverse effects on prenatal and postnatal development were reported in the offspring of animals at doses approximately 10 times the human exposure (Prod Info VIBERZI oral tablets, 2015).

a) There were decreases in neonatal body weight and survival rates at birth and during lactation when subQ nalbuphine was given at doses approximately 4 times the maximum recommended human dose to female and male rats prior to mating and throughout gestation and lactation or to pregnant rats during the last third of gestation and throughout lactation (Prod Info nalbuphine hydrochloride subcutaneous injection, IM injection, IV injection, solution, 2007).

a) Eluxadoline was detected in the milk of lactating animals after administration of doses 1.8, 3, and 10 times the human exposure (Prod Info VIBERZI oral tablets, 2015).

a) After ingestion of poppy seeds, opioids show up in the urine within 5 hours (Beck et al, 1990).
b) Soaking the seeds in water removed 45.6% of free morphine and 48.4% of free codeine (Lo & Chua, 1992). Soaked seeds have less potential for producing elevated urine levels.

a) The Department of Defense (DOD) and Health and Human Services (HHS) have set an opiate urine screening cutoff concentration of 2000 ng/mL and a confirmation cutoff concentration for total morphine of either 2000 ng/mL (HHS) or 4000 ng/mL (DOD). A specific heroin marker, 6-acetylmorphine (6-AM), was added to the testing if a urine tested positive for morphine. A cutoff for 6-AM is 10 ng/mL. A test coming back above the cutoffs for both morphine and heroin are considered positive for heroin. A test above the cutoff for morphine but not for heroin is considered positive for morphine (Moore et al, 2001).
b) A urinary codeine concentration (following multiple doses of anti-cough syrup) larger than 300 ng/mL and the ratio of morphine to codeine to be less than 3 has been proposed as criteria for a positive codeine intake (as opposed to morphine) (Hsu et al, 2000).

a) Past opiate usage can be detected by means of hair analysis as well as the diagnosis of poisoning associated with opiate addiction. Hair analysis may be accomplished by means of RIA, HPLC, or GC/MS. Hair analysis may provide both hair drug content and hair profile. A single opiate ingestion may not be detectable through hair analysis, which may be a drawback of this method (Staub, 1993). GC/MS method has been used for analyzing cocaine and its metabolites, opiates, and cannabinoids in human hair (Jurado et al, 1995).

a) On site saliva drug testing (Cozart RapiScan), which detects the parent drug for opiates, is based on the principle of competitive lateral flow immunoassay using digital photography to provide a semi-quantitative end point. Sensitivity and specificity were both 100% for codeine for 9 hours after ingestion. Tests are positive as long as codeine saliva concentrations are above 5 ng/mL by GC/MS (Jehanli et al, 2001).

1) The detection limit (sensitivity) is 0.5 mcg/mL for morphine or its equivalent.
2) The assays do not detect long-acting methadone, L-alpha-acetyl-methadol (LAAM), or its metabolites.
3) CDC proficiency testing and clinical studies show this method to correlate well with GC, GLC, HPLC, RIA, and TLC.
4) RELIABILITY

1) CASE REPORT: An 18-year-old boy with a past medical history of IV heroin abuse, developed hemoptysis, acute lung injury, hypoxic respiratory failure, and diffuse alveolar hemorrhage, after snorting an unknown amount of butyrfentanyl instead of acetyl fentanyl. Fentanyl and opiates immunoassays were both positive, but fentanyl was not present in high-performance liquid chromatography and mass spectrometry. Butyrfentanyl was detected using a high-performance gas chromatography obtained from the Bureau of Criminal Apprehension. Following further supportive care, his condition improved gradually and he was extubated on day 4 and discharged 3 days later after receiving treatment for ventilator-associated pneumonia (Cole et al, 2015).

a) Naloxone, a pure opioid antagonist, reverses coma and respiratory depression from all opioids. It has no agonist effects and can safely be employed in a mixed or unknown overdose where it can be diagnostic and therapeutic without risk to the patient.
b) Indicated in patients with mental status and respiratory depression possibly related to opioid overdose (Hoffman et al, 1991).
c) DOSE: The initial dose of naloxone should be low (0.04 to 0.4 mg) with a repeat dosing as needed or dose escalation to 2 mg as indicated due to the risk of opioid withdrawal in an opioid-tolerant individual; if delay in obtaining venous access, may administer subcutaneously, intramuscularly, intranasally, via nebulizer (in a patient with spontaneous respirations) or via an endotracheal tube (Vanden Hoek,TL,et al).
d) Recurrence of opioid toxicity has been reported to occur in approximately 1 out of 3 adult ED opioid overdose cases after a response to naloxone. Recurrences are more likely with long-acting opioids (Watson et al, 1998)

a) INITIAL BOLUS DOSE: Because naloxone can produce opioid withdrawal in an opioid-dependent individual leading to severe agitation and hypertension, the initial dose of naloxone should be low (0.04 to 0.4 mg) with a repeat dosing as needed or dose escalation to 2 mg as indicated (Vanden Hoek,TL,et al).
b) Larger doses may be needed to reverse opioid effects. Generally, if no response is observed after 8 to 10 milligrams has been administered, the diagnosis of opioid-induced respiratory depression should be questioned (Howland & Nelson, 2011; Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008). Very large doses of naloxone (10 milligrams or more) may be required to reverse the effects of a buprenorphine overdose (Gal, 1989; Jasinski et al, 1978).
c) REPEAT DOSE: The effective naloxone dose may have to be repeated every 20 to 90 minutes due to the much longer duration of action of the opioid agonist used(Howland & Nelson, 2011).
d) NALOXONE DOSE/CHILDREN
e) NALOXONE DOSE/NEONATE
f) NALOXONE/ALTERNATE ROUTES
g) NALOXONE/CONTINUOUS INFUSION METHOD
h) NALOXONE/PREGNANCY

a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.

a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
b) ADVERSE EFFECTS/CONTRAINDICATIONS

a) Naloxone, a pure opioid antagonist, reverses coma and respiratory depression from all opioids. It has no agonist effects and can safely be employed in a mixed or unknown overdose where it can be diagnostic and therapeutic without risk to the patient.
b) Indicated in patients with mental status and respiratory depression possibly related to opioid overdose (Hoffman et al, 1991).
c) DOSE: The initial dose of naloxone should be low (0.04 to 0.4 mg) with a repeat dosing as needed or dose escalation to 2 mg as indicated due to the risk of opioid withdrawal in an opioid-tolerant individual; if delay in obtaining venous access, may administer subcutaneously, intramuscularly, intranasally, via nebulizer (in a patient with spontaneous respirations) or via an endotracheal tube (Vanden Hoek,TL,et al).
d) Recurrence of opioid toxicity has been reported to occur in approximately 1 out of 3 adult ED opioid overdose cases after a response to naloxone. Recurrences are more likely with long-acting opioids (Watson et al, 1998)

a) INITIAL BOLUS DOSE: Because naloxone can produce opioid withdrawal in an opioid-dependent individual leading to severe agitation and hypertension, the initial dose of naloxone should be low (0.04 to 0.4 mg) with a repeat dosing as needed or dose escalation to 2 mg as indicated (Vanden Hoek,TL,et al).
b) Larger doses may be needed to reverse opioid effects. Generally, if no response is observed after 8 to 10 milligrams has been administered, the diagnosis of opioid-induced respiratory depression should be questioned (Howland & Nelson, 2011; Prod Info naloxone HCl IV, IM, subcutaneous injection solution, 2008). Very large doses of naloxone (10 milligrams or more) may be required to reverse the effects of a buprenorphine overdose (Gal, 1989; Jasinski et al, 1978).
c) REPEAT DOSE: The effective naloxone dose may have to be repeated every 20 to 90 minutes due to the much longer duration of action of the opioid agonist used(Howland & Nelson, 2011).
d) NALOXONE DOSE/CHILDREN
e) NALOXONE DOSE/NEONATE
f) NALOXONE/ALTERNATE ROUTES
g) NALOXONE/CONTINUOUS INFUSION METHOD
h) NALOXONE/PREGNANCY

a) ALTERNATIVE ROUTES: If IV access is unavailable, the intramuscular or subcutaneous route may be used. However, the effect of a 1 mg dose may delayed by 5 to 15 minutes (Howland, 2006a).
b) WITHDRAWAL SYNDROME: Using higher dosages or shorter intervals is likely to increase the risk of symptoms related to acute withdrawal (i.e., nausea, vomiting, elevated blood pressure, and anxiety) (Prod Info REVEX(R) injection, 2006).

a) To minimize barotrauma and other complications, use the lowest amount of PEEP possible while maintaining adequate oxygenation. Use of smaller tidal volumes (6 mL/kg) and lower plateau pressures (30 cm water or less) has been associated with decreased mortality and more rapid weaning from mechanical ventilation in patients with ARDS (Brower et al, 2000). More treatment information may be obtained from ARDS Clinical Network website, NIH NHLBI ARDS Clinical Network Mechanical Ventilation Protocol Summary, http://www.ardsnet.org/node/77791 (NHLBI ARDS Network, 2008)

a) ADULT DOSE: Initially 5 to 10 mg IV, OR 0.15 mg/kg IV up to 10 mg per dose up to a rate of 5 mg/minute; may be repeated every 5 to 20 minutes as needed (Brophy et al, 2012; Prod Info diazepam IM, IV injection, 2008; Manno, 2003).
b) PEDIATRIC DOSE: 0.1 to 0.5 mg/kg IV over 2 to 5 minutes; up to a maximum of 10 mg/dose. May repeat dose every 5 to 10 minutes as needed (Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008).
c) Monitor for hypotension, respiratory depression, and the need for endotracheal intubation. Consider a second agent if seizures persist or recur after repeated doses of diazepam .

a) DIAZEPAM may be given rectally or intramuscularly (Manno, 2003). RECTAL DOSE: CHILD: Greater than 12 years: 0.2 mg/kg; 6 to 11 years: 0.3 mg/kg; 2 to 5 years: 0.5 mg/kg (Brophy et al, 2012).
b) MIDAZOLAM has been used intramuscularly and intranasally, particularly in children when intravenous access has not been established. ADULT DOSE: 0.2 mg/kg IM, up to a maximum dose of 10 mg (Brophy et al, 2012). PEDIATRIC DOSE: INTRAMUSCULAR: 0.2 mg/kg IM, up to a maximum dose of 7 mg (Chamberlain et al, 1997) OR 10 mg IM (weight greater than 40 kg); 5 mg IM (weight 13 to 40 kg); INTRANASAL: 0.2 to 0.5 mg/kg up to a maximum of 10 mg/dose (Loddenkemper & Goodkin, 2011; Brophy et al, 2012). BUCCAL midazolam, 10 mg, has been used in adolescents and older children (5-years-old or more) to control seizures when intravenous access was not established (Scott et al, 1999).

a) MAXIMUM RATE: The rate of intravenous administration of lorazepam should not exceed 2 mg/min (Brophy et al, 2012; Prod Info lorazepam IM, IV injection, 2008).
b) ADULT DOSE: 2 to 4 mg IV initially; repeat every 5 to 10 minutes as needed, if seizures persist (Manno, 2003; Brophy et al, 2012).
c) PEDIATRIC DOSE: 0.05 to 0.1 mg/kg IV over 2 to 5 minutes, up to a maximum of 4 mg/dose; may repeat in 5 to 15 minutes as needed, if seizures continue (Brophy et al, 2012; Loddenkemper & Goodkin, 2011; Hegenbarth & American Academy of Pediatrics Committee on Drugs, 2008; Sreenath et al, 2009; Chin et al, 2008).

a) ADULT LOADING DOSE: 20 mg/kg IV at an infusion rate of 50 to 100 mg/minute IV. An additional 5 to 10 mg/kg dose may be given 10 minutes after loading infusion if seizures persist or recur (Brophy et al, 2012).
b) Patients receiving high doses will require endotracheal intubation and may require vasopressor support (Brophy et al, 2012).
c) PEDIATRIC LOADING DOSE: 20 mg/kg may be given as single or divided application (2 mg/kg/minute in children weighing less than 40 kg up to 100 mg/min in children weighing greater than 40 kg). A plasma concentration of about 20 mg/L will be achieved by this dose (Loddenkemper & Goodkin, 2011).
d) REPEAT PEDIATRIC DOSE: Repeat doses of 5 to 20 mg/kg may be given every 15 to 20 minutes if seizures persist, with cardiorespiratory monitoring (Loddenkemper & Goodkin, 2011).
e) MONITOR: For hypotension, respiratory depression, and the need for endotracheal intubation (Loddenkemper & Goodkin, 2011; Manno, 2003).
f) SERUM CONCENTRATION MONITORING: Monitor serum concentrations over the next 12 to 24 hours. Therapeutic serum concentrations of phenobarbital range from 10 to 40 mcg/mL, although the optimal plasma concentration for some individuals may vary outside this range (Hvidberg & Dam, 1976; Choonara & Rane, 1990; AMA Department of Drugs, 1992).

a) If seizures persist after phenobarbital, propofol or pentobarbital infusion, or neuromuscular paralysis with general anesthesia (isoflurane) and continuous EEG monitoring should be considered (Manno, 2003). Other anticonvulsants can be considered (eg, valproate sodium, levetiracetam, lacosamide, topiramate) if seizures persist or recur; however, there is very little data regarding their use in toxin induced seizures, controlled trials are not available to define the optimal dosage ranges for these agents in status epilepticus (Brophy et al, 2012):

a) Infuse 10 to 20 milliliters/kilogram of isotonic fluid and keep the patient supine. If hypotension persists, administer dopamine or norepinephrine. Consider central venous pressure monitoring to guide further fluid therapy.

a) DOSE: Begin at 5 micrograms per kilogram per minute progressing in 5 micrograms per kilogram per minute increments as needed (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). If hypotension persists, dopamine may need to be discontinued and a more potent vasoconstrictor (eg, norepinephrine) should be considered (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).
b) CAUTION: If ventricular dysrhythmias occur, decrease rate of administration (Prod Info dopamine hcl, 5% dextrose IV injection, 2004). Extravasation may cause local tissue necrosis, administration through a central venous catheter is preferred (Prod Info dopamine hcl, 5% dextrose IV injection, 2004).

a) PREPARATION: 4 milligrams (1 amp) added to 1000 milliliters of diluent provides a concentration of 4 micrograms/milliliter of norepinephrine base. Norepinephrine bitartrate should be mixed in dextrose solutions (dextrose 5% in water, dextrose 5% in saline) since dextrose-containing solutions protect against excessive oxidation and subsequent potency loss. Administration in saline alone is not recommended (Prod Info norepinephrine bitartrate injection, 2005).
b) DOSE

a) Benzodiazepines are the mainstay of therapy. Cyproheptadine, a 5-HT antagonist, is also commonly used. Severe cases have been managed with benzodiazepine sedation and neuromuscular paralysis with non-depolarizing agents(Claassen & Gelissen, 2005).

a) Control agitation and muscle activity. Undress patient and enhance evaporative heat loss by keeping skin damp and using cooling fans.
b) MUSCLE ACTIVITY: Benzodiazepines are the drug of choice to control agitation and muscle activity. DIAZEPAM: ADULT: 5 to 10 mg IV every 5 to 10 minutes as needed, monitor for respiratory depression and need for intubation. CHILD: 0.25 mg/kg IV every 5 to 10 minutes; monitor for respiratory depression and need for intubation.
c) Non-depolarizing paralytics may be used in severe cases.

a) Cyproheptadine is a non-specific 5-HT antagonist that has been shown to block development of serotonin syndrome in animals (Sternbach, 1991). Cyproheptadine has been used in the treatment of serotonin syndrome (Mills, 1997; Goldberg & Huk, 1992). There are no controlled human trials substantiating its efficacy.
b) ADULT: 12 mg initially followed by 2 mg every 2 hours if symptoms persist, up to a maximum of 32 mg in 24 hours. Maintenance dose 8 mg orally repeated every 6 hours (Boyer & Shannon, 2005).
c) CHILD: 0.25 mg/kg/day divided every 6 hours, maximum dose 12 mg/day (Mills, 1997).

a) Monitor vital signs regularly. For mild/moderate asymptomatic hypertension, pharmacologic intervention is usually not necessary.

a) Administer 10 to 20 mL/kg 0.9% saline bolus and place patient supine. Further fluid therapy should be guided by central venous pressure or right heart catheterization to avoid volume overload.
b) Pressor agents with dopaminergic effects may theoretically worsen serotonin syndrome and should be used with caution. Direct acting agents (norepinephrine, epinephrine, phentolamine) are theoretically preferred.
c) NOREPINEPHRINE

a) DIAZEPAM
b) LORAZEPAM
c) RECURRING SEIZURES
d) PHENOBARBITAL

a) Chlorpromazine is a 5-HT2 receptor antagonist that has been used to treat cases of serotonin syndrome (Graham, 1997; Gillman, 1996). Controlled human trial documenting its efficacy are lacking.
b) ADULT: 25 to 100 mg intramuscularly repeated in 1 hour if necessary.
c) CHILD: 0.5 to 1 mg/kg repeated as needed every 6 to 12 hours not to exceed 2 mg/kg/day.

a) BROMOCRIPTINE: It has been used in the treatment of neuroleptic malignant syndrome but is NOT RECOMMENDED in the treatment of serotonin syndrome as it has serotonergic effects (Gillman, 1997). In one case the use of bromocriptine was associated with a fatal outcome (Kline et al, 1989).

a) The goal of therapy for analgesia is to use the smallest effective dose. The following summarizes usual adult dosages.
b) Please refer to the manufacturer's information for more specific information on individual agents.

a) To accelerate the time to upper and lower gastrointestinal recovery following partial large or small bowel resection surgery or primary anastomosis: 12 mg (1 capsule) given 30 minutes to 5 hours prior to surgery followed by 12 mg twice daily beginning the day after surgery for a maximum of 7 days; MAXIMUM: 15 doses. Alvimopan is only distributed to hospitals that have registered and are participating in the ENTEREG(R) Access Support and Education (EASE) program (Call 1-877-282-4786 for further information) (Prod Info ENTEREG(R) oral capsules, 2012).

a) ORAL: USUAL DOSE: 100 mg orally 2 times daily (Prod Info VIBERZI oral tablets, 2015).
b) ORAL: DOSE IN PATIENTS WHO DO NOT HAVE A GALLBLADDER: 75 mg orally 2 times daily (Prod Info VIBERZI oral tablets, 2015).

a) ORAL: 10% tincture, 0.6 mL 4 times daily; maximum 6 mL/day (Prod Info opium tincture, 2003)
b) ORAL: Paregoric (2 mg morphine per 5 mL), 5-10 mL 1 to 4 times daily. Maximum 40 mL/day (Prod Info Paregoric, 1998).
c) RECTAL: 30 to 60 mg once to twice daily not to exceed 4 doses daily (Prod Info B&O SUPPRETTES(R) No. 15A and No. 16A rectal suppositories, 2002).

a) NOTE: Remifentanil is not recommended as the sole agent in general anesthesia because loss of consciousness cannot be assured and because of a high incidence of apnea, muscle rigidity, and tachycardia. It is synergistic with other anesthetics, and the doses of thiopental, propofol, isoflurane, and midazolam may need to be reduced by up to 75% with concomitant administration of remifentanil. Administration must be individualized based on patient response (Prod Info Ultiva(R), remifentanil hydrochloride, 1999).
b) PARENTERAL: IV infusion of 0.5 to 1 mcg/kg/min, with an initial dose of 1 mcg/kg administered over 30 to 60 seconds for general anesthesia and continuing as an analgesic (Prod Info Ultiva(R), remifentanil hydrochloride, 1996).

a) PARENTERAL: 8 to 30 mcg/kg IV with 100% oxygen and a muscle relaxant, then 0.5 to 10 mcg/kg as needed in response to signs of lightening of anesthesia. Maximum dose of 30 mcg/kg/procedure (Prod Info sufentanil citrate injection, 2003).

a) The following table presents approximate equivalent analgesic doses for various opioids. These doses are primarily based on single-dose studies in healthy adults and do not reflect individual variation due to tolerance, weight or age.

a) The goal of therapy for analgesia is to use the smallest effective dose. The following summarizes usual pediatric dosages.
b) Please refer to manufacturer's information for more specific information on individual agents.

a) Safety and effectiveness have not been established in pediatric patients (Prod Info VIBERZI oral tablets, 2015).

a) PARENTERAL (Initial): 0.25 micrograms/kilogram/minute (Prod Info Ultiva(R), 2004)
b) PARENTERAL (Maintenance): 0.05 to 1.3 micrograms/kilogram/minute; supplemental doses of 1 micrograms/kilogram every 2 to 5 min if needed (Prod Info Ultiva(R), 2004)

a) PARENTERAL: 10 to 25 micrograms/kilogram with 100% oxygen, additional doses of up to 25 to 50 micrograms for maintenance of anesthesia (Prod Info sufentanil citrate injection, 2003).

a) REMIFENTANIL

a) AH-7921
b) ALFENTANIL
c) ALPHAPRODINE
d) ANILERIDINE
e) HEROIN
f) METHYLFENTANYL
g) SUFENTANIL

a) Begin treatment immediately.
b) Keep animal warm and do not handle unnecessarily.
c) Remove the patient and other animals from the source of contamination or remove dietary sources.

a) ASPCA Animal Poison Control Center, 1717 S Philo Road, Suite 36 Urbana, IL 61802
b) It is an emergency telephone service which provides toxicology information to veterinarians, animal owners, universities, extension personnel and poison center staff for a fee. A veterinary toxicologist is available for consultation.
c) Contact information: (888) 426-4435 (hotline) or www.aspca.org (A fee may apply. Please inquire with the poison center). The agency will make follow-up calls as needed in critical cases at no extra charge.

a) EMESIS/GASTRIC LAVAGE -
b) ACTIVATED CHARCOAL/CATHARTIC -

a) Administer naloxone 0.02 milligram/kilogram (1 milliliter per 40 pounds body weight) intramuscularly, or intravenously if patient is in shock or severe respiratory depression.

a) SEIZURES/LARGE ANIMALS: May be controlled with diazepam.
b) SEIZURES/DOGS & CATS:

a) FLUIDS: Begin intravenous administration of lactated ringers or other solution at a rate of up to 60 milliliters/kilograms/hour.
b) DOPAMINE: If the patient does not respond to volume loading, administer dopamine (DOGS & CATS) at a dose not to exceed 2 to 5 micrograms/kilogram/minute.
c) DOBUTAMINE: If inadequate cardiac function is contributing to poor peripheral perfusion, administer dobutamine (DOGS & CATS): 3 to 10 micrograms/kilogram/minute.
d) NOREPINEPHRINE:

a) Admit all symptomatic patients and begin treatment.
b) Keep the patient for 8 hours after cessation of clinical signs in case of relapse.

1) SUMMARY
2) Treatment should always be done on the advice and with the consultation of a veterinarian.
3) Additional information regarding treatment of poisoned animals may be obtained from a Veterinary Toxicologist or the National Animal Poison Control Center.
4) ASPCA ANIMAL POISON CONTROL CENTER

1) GENERAL TREATMENT