Clinical Effects
USES:
Morphine is primarily used for the treatment of pain. Morphine may be abused for euphoric effects by multiple routes (ie, injection, insufflation, smoking, ingestion).
EPIDEMIOLOGY: Overdose is not common, but may be more common in patients with chronic opioid abuse or dependence, and may be life threatening.
PHARMACOLOGY:
Morphine binds primarily at the Mu opiate receptors at therapeutic doses. Morphine is an opiate, a group of naturally occurring compounds derived from the poppy, Papaver somniferum
TOXICOLOGY
Therapeutic and toxic effects are mediated by different opioid receptors. Mu 1: Supraspinal and peripheral analgesia, sedation, and euphoria. Mu 2: Spinal analgesia, respiratory depression, physical dependence, GI dysmotility, bradycardia and pruritus. Kappa 1: Spinal analgesia and miosis. Kappa 2: Dysphoria and psychotomimesis. Kappa 3: Supraspinal analgesia. Chronic opioid users develop tolerance to the analgesic and euphoric effects, but not to the respiratory depression effects.
OVERDOSE:
MILD TO MODERATE POISONING: Euphoria, drowsiness, constipation, nausea, vomiting and pinpoint pupils. Mild bradycardia or hypotension may be present. SEVERE POISONING: Respiratory depression leading to apnea, hypoxia, coma, bradycardia, or acute lung injury. Rarely, seizures may develop from hypoxia. Death may result from any of these complications. INTRATHECA LINJECTION: Hypotension, respiratory depression, hypertension, CNS depression, agitation, and protracted seizures have been reported after intrathecal morphine overdose. EPIDURAL OVERDOSE: Even large epidural overdoses have only caused CNS and respiratory depression.
Treatment
Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Patients may only need observation. MANAGEMENT OF SEVERE TOXICITY: Administer oxygen and assist ventilation for respiratory depression. Naloxone is the antidote indicated for severe toxicity (respiratory or CNS depression). Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone, or in patients who develop severe acute lung injury.
Decontamination:
PREHOSPITAL: Morphine overdoses may be life-threatening. Activated charcoal should be considered early after a significant oral ingestion, if a patient can protect their airway and is without significant signs of toxicity. If a patient is displaying signs of moderate to severe toxicity, do NOT administer activated charcoal because of the risk of aspiration. HOSPITAL: Consider activated charcoal if a patient presents soon after an ingestion and is not manifesting signs and symptoms of toxicity. Activated charcoal is generally not recommended in patients with significant signs of toxicity because of the risk of aspiration. Gastric lavage is not recommended as patients usually do well with supportive care.
Airway management:
Administer oxygen and assist ventilation for respiratory depression. Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone, or in patients who develop severe acute lung injury.
Antidote:
NALOXONE, an opioid antagonist, is the specific antidote. Naloxone can be given intravascularly, intramuscularly, subcutaneously, intranasally or endotracheally. The usual dose is 0.4 to 2.0 mg IV. In patients with suspected opioid dependence, incremental doses of 0.2 mg IV should be administered, titrated to reversal of respiratory depression and coma, to avoid precipitating acute opioid withdrawal. Doses may be repeated every 2 to 3 minutes up to 20 mg. Very high doses are rarely needed. A CONTINUOUS infusion is likely to be necessary after a controlled-release morphine ingestion. A suggested starting rate is two-thirds of the dose effective for initial reversal that is administered each hour; titrate as needed. DURATION of effect is usually 1 to 2 hours. Morphine has a longer duration of effect, so it is necessary to observe the patient at least 4 hours after the last dose of naloxone to ensure that the patient does not have recurrent symptoms of toxicity. Naloxone can precipitate withdrawal in an opioid-dependent patients, which is usually not life-threatening; however it can be extremely uncomfortable for the patient.
Seizure:
Seizures are rare, but may be a result of hypoxia. Treatment includes ensuring adequate oxygenation, and administering intravenous benzodiazepines; propofol or barbiturates may be indicated, if seizures persist. Patients with seizures and myoclonus after massive intrathecal morphine overdose have required barbiturate coma with continuous EEG monitoring.
Acute lung injury:
Acute lung injury can develop in a small proportion of patients after an acute opioid overdose. The pathophysiology is unclear. Patients should be observed for 4 to 6 hours after overdose to evaluate for hypoxia and/or the development of acute lung injury. Continuous oxygen therapy, pulse oximetry, PEEP and mechanical ventilation may be necessary.
Hypotensive episode:
Hypotension is often reversed by naloxone. Initially treat with a saline bolus, if patient can tolerate a fluid load; then add adrenergic vasopressors to raise mean arterial pressure if hypotension persists.
Intrathecal injection:
Massive intrathecal overdose can cause severe toxicity. Keep the patient upright if possible (may not be useful unless overdose is recognized immediately if solution is isobaric). Immediately drain AT LEAST 20 mL CSF; drainage of up to 70 mL has been tolerated in adults. Follow with CSF exchange (remove serial 20 mL aliquots CSF and replace with equivalent volumes of warmed, preservative free normal saline or lactated ringers). Consult a neurosurgeon immediately for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline or lactated ringers through ventricular catheter, drain fluid from lumbar catheter). The optimal volume and duration is not known. In one case, irrigation with 900 mL of lactated ringers over 1 hour was associated with a 97% reduction in CSF morphine concentration.
Monitoring of patient:
Monitor vital signs frequently, pulse oximetry, and continuous cardiac monitoring. Monitor for CNS and respiratory depression. Morphine plasma levels are not clinically useful or readily available. Urine toxicology screens may confirm exposure, but are rarely useful in guiding therapy. Obtain acetaminophen and salicylate concentrations levels in a patient with a suspected overdose. Routine lab work is usually not indicated, unless it is helpful to rule out other causes or if the diagnosis of opioid toxicity is uncertain. Obtain a chest x-ray for persistent hypoxia. Consider a head CT and/or lumbar puncture to rule out an intracranial mass, bleeding or infection, if the diagnosis is uncertain.
Enhanced elimination procedure: Hemodialysis and hemoperfusion are not of value because of the large volume of distribution.
Patient disposition: HOME CRITERIA:
Respiratory depression may occur at doses just above a therapeutic dose. Children should be evaluated in the hospital and observed as they are generally opioid-naive and may develop respiratory depression. Adults should be evaluated by a health care professional if they have received a higher than recommended (therapeutic) dose, especially if opioid-naive.
OBSERVATION CRITERIA
Patients with deliberate ingestions and all children with ingestions should be sent to a health care facility for observation for at least 4 hours, as peak plasma levels and symptoms will likely develop within this time period. Patients that have ingested a sustained-release or long-acting product have the potential to manifest symptoms in a delayed fashion and should be observed for 12 to 24 hours. Patients who are treated with naloxone should be observed for 4 to 6 hours after the last dose, for recurrent CNS depression or acute lung injury.
ADMISSION CRITERIA:
Patients with significant persistent central nervous depression should be admitted to the hospital. Patients needing more than 2 doses of naloxone should be admitted as they may have taken a longer-acting opioid and may need additional doses. Patients with coma, seizures, dysrhythmias, or delirium or those needing a naloxone infusion or intubated patients should be admitted to an intensive care setting. Patients with overdose of sustained release products who develop significant CNS or respiratory depression should be admitted.
CONSULT CRITERIA:
Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear. Refer patients for substance abuse counseling if indicated.
Range Of Toxicity
TOXICITY
The toxicity of morphine for an individual varies with tolerance developed from habitual use. In general, infants and children have unusual sensitivity to opioid agents. With timely administration of naloxone and respiratory support, patients will generally survive overdoses that would otherwise be lethal. Massive intrathecal overdose (in the range of 250 mg to 510 mg) causes life-threatening toxicity.
USES:
Morphine is primarily used for the treatment of pain. Morphine may be abused for euphoric effects by multiple routes (ie, injection, insufflation, smoking, ingestion).
EPIDEMIOLOGY: Overdose is not common, but may be more common in patients with chronic opioid abuse or dependence, and may be life threatening.
PHARMACOLOGY:
Morphine binds primarily at the Mu opiate receptors at therapeutic doses. Morphine is an opiate, a group of naturally occurring compounds derived from the poppy, Papaver somniferum
TOXICOLOGY
Therapeutic and toxic effects are mediated by different opioid receptors. Mu 1: Supraspinal and peripheral analgesia, sedation, and euphoria. Mu 2: Spinal analgesia, respiratory depression, physical dependence, GI dysmotility, bradycardia and pruritus. Kappa 1: Spinal analgesia and miosis. Kappa 2: Dysphoria and psychotomimesis. Kappa 3: Supraspinal analgesia. Chronic opioid users develop tolerance to the analgesic and euphoric effects, but not to the respiratory depression effects.
OVERDOSE:
MILD TO MODERATE POISONING: Euphoria, drowsiness, constipation, nausea, vomiting and pinpoint pupils. Mild bradycardia or hypotension may be present. SEVERE POISONING: Respiratory depression leading to apnea, hypoxia, coma, bradycardia, or acute lung injury. Rarely, seizures may develop from hypoxia. Death may result from any of these complications. INTRATHECA LINJECTION: Hypotension, respiratory depression, hypertension, CNS depression, agitation, and protracted seizures have been reported after intrathecal morphine overdose. EPIDURAL OVERDOSE: Even large epidural overdoses have only caused CNS and respiratory depression.
Treatment
Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Patients may only need observation. MANAGEMENT OF SEVERE TOXICITY: Administer oxygen and assist ventilation for respiratory depression. Naloxone is the antidote indicated for severe toxicity (respiratory or CNS depression). Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone, or in patients who develop severe acute lung injury.
Decontamination:
PREHOSPITAL: Morphine overdoses may be life-threatening. Activated charcoal should be considered early after a significant oral ingestion, if a patient can protect their airway and is without significant signs of toxicity. If a patient is displaying signs of moderate to severe toxicity, do NOT administer activated charcoal because of the risk of aspiration. HOSPITAL: Consider activated charcoal if a patient presents soon after an ingestion and is not manifesting signs and symptoms of toxicity. Activated charcoal is generally not recommended in patients with significant signs of toxicity because of the risk of aspiration. Gastric lavage is not recommended as patients usually do well with supportive care.
Airway management:
Administer oxygen and assist ventilation for respiratory depression. Orotracheal intubation for airway protection should be performed early in cases of obtundation and/or respiratory depression that do not respond to naloxone, or in patients who develop severe acute lung injury.
Antidote:
NALOXONE, an opioid antagonist, is the specific antidote. Naloxone can be given intravascularly, intramuscularly, subcutaneously, intranasally or endotracheally. The usual dose is 0.4 to 2.0 mg IV. In patients with suspected opioid dependence, incremental doses of 0.2 mg IV should be administered, titrated to reversal of respiratory depression and coma, to avoid precipitating acute opioid withdrawal. Doses may be repeated every 2 to 3 minutes up to 20 mg. Very high doses are rarely needed. A CONTINUOUS infusion is likely to be necessary after a controlled-release morphine ingestion. A suggested starting rate is two-thirds of the dose effective for initial reversal that is administered each hour; titrate as needed. DURATION of effect is usually 1 to 2 hours. Morphine has a longer duration of effect, so it is necessary to observe the patient at least 4 hours after the last dose of naloxone to ensure that the patient does not have recurrent symptoms of toxicity. Naloxone can precipitate withdrawal in an opioid-dependent patients, which is usually not life-threatening; however it can be extremely uncomfortable for the patient.
Seizure:
Seizures are rare, but may be a result of hypoxia. Treatment includes ensuring adequate oxygenation, and administering intravenous benzodiazepines; propofol or barbiturates may be indicated, if seizures persist. Patients with seizures and myoclonus after massive intrathecal morphine overdose have required barbiturate coma with continuous EEG monitoring.
Acute lung injury:
Acute lung injury can develop in a small proportion of patients after an acute opioid overdose. The pathophysiology is unclear. Patients should be observed for 4 to 6 hours after overdose to evaluate for hypoxia and/or the development of acute lung injury. Continuous oxygen therapy, pulse oximetry, PEEP and mechanical ventilation may be necessary.
Hypotensive episode:
Hypotension is often reversed by naloxone. Initially treat with a saline bolus, if patient can tolerate a fluid load; then add adrenergic vasopressors to raise mean arterial pressure if hypotension persists.
Intrathecal injection:
Massive intrathecal overdose can cause severe toxicity. Keep the patient upright if possible (may not be useful unless overdose is recognized immediately if solution is isobaric). Immediately drain AT LEAST 20 mL CSF; drainage of up to 70 mL has been tolerated in adults. Follow with CSF exchange (remove serial 20 mL aliquots CSF and replace with equivalent volumes of warmed, preservative free normal saline or lactated ringers). Consult a neurosurgeon immediately for placement of a ventricular catheter and begin ventriculolumbar perfusion (infuse warmed preservative free normal saline or lactated ringers through ventricular catheter, drain fluid from lumbar catheter). The optimal volume and duration is not known. In one case, irrigation with 900 mL of lactated ringers over 1 hour was associated with a 97% reduction in CSF morphine concentration.
Monitoring of patient:
Monitor vital signs frequently, pulse oximetry, and continuous cardiac monitoring. Monitor for CNS and respiratory depression. Morphine plasma levels are not clinically useful or readily available. Urine toxicology screens may confirm exposure, but are rarely useful in guiding therapy. Obtain acetaminophen and salicylate concentrations levels in a patient with a suspected overdose. Routine lab work is usually not indicated, unless it is helpful to rule out other causes or if the diagnosis of opioid toxicity is uncertain. Obtain a chest x-ray for persistent hypoxia. Consider a head CT and/or lumbar puncture to rule out an intracranial mass, bleeding or infection, if the diagnosis is uncertain.
Enhanced elimination procedure: Hemodialysis and hemoperfusion are not of value because of the large volume of distribution.
Patient disposition: HOME CRITERIA:
Respiratory depression may occur at doses just above a therapeutic dose. Children should be evaluated in the hospital and observed as they are generally opioid-naive and may develop respiratory depression. Adults should be evaluated by a health care professional if they have received a higher than recommended (therapeutic) dose, especially if opioid-naive.
OBSERVATION CRITERIA
Patients with deliberate ingestions and all children with ingestions should be sent to a health care facility for observation for at least 4 hours, as peak plasma levels and symptoms will likely develop within this time period. Patients that have ingested a sustained-release or long-acting product have the potential to manifest symptoms in a delayed fashion and should be observed for 12 to 24 hours. Patients who are treated with naloxone should be observed for 4 to 6 hours after the last dose, for recurrent CNS depression or acute lung injury.
ADMISSION CRITERIA:
Patients with significant persistent central nervous depression should be admitted to the hospital. Patients needing more than 2 doses of naloxone should be admitted as they may have taken a longer-acting opioid and may need additional doses. Patients with coma, seizures, dysrhythmias, or delirium or those needing a naloxone infusion or intubated patients should be admitted to an intensive care setting. Patients with overdose of sustained release products who develop significant CNS or respiratory depression should be admitted.
CONSULT CRITERIA:
Consult a poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear. Refer patients for substance abuse counseling if indicated.
Range Of Toxicity
TOXICITY
The toxicity of morphine for an individual varies with tolerance developed from habitual use. In general, infants and children have unusual sensitivity to opioid agents. With timely administration of naloxone and respiratory support, patients will generally survive overdoses that would otherwise be lethal. Massive intrathecal overdose (in the range of 250 mg to 510 mg) causes life-threatening toxicity.
Anda baru saja membaca artikel yang berkategori Morphine /
pharmacology /
Toxicity
dengan judul Morphine Pharmacology Over Dose Treatment and Range Of Toxicity. Anda bisa bookmark halaman ini dengan URL https://medipub.blogspot.com/2011/04/morphine-pharmacology-over-dose_19.html. Terima kasih!
Ditulis oleh:
Unknown - Tuesday, 19 April 2011
