What are the manifestations of morphine toxicity and how is it managed?

Morphine Toxicity: Manifestations and Management

Morphine toxicity primarily manifests as respiratory depression, CNS depression (drowsiness, confusion, hallucinations, myoclonic jerks), cardiovascular effects (hypotension, bradycardia), and gastrointestinal symptoms (nausea, vomiting, constipation), with management centered on immediate naloxone administration and supportive care. 1

Clinical Manifestations

Respiratory System (Most Critical)

• Respiratory depression is the primary and most life-threatening manifestation of morphine toxicity 1
• Occurs more frequently in elderly, debilitated patients, and those with hypoxia, hypercapnia, or upper airway obstruction 1
• Severe cases progress to apnea, requiring immediate intervention 1
• Rapid IV administration can cause chest wall rigidity 1
• Patients with COPD, cor pulmonale, or decreased respiratory reserve face substantially increased risk 1

Central Nervous System Toxicity

• CNS manifestations include drowsiness, cognitive impairment, confusion, hallucinations, and myoclonic jerks 2
• High doses given intravenously can cause CNS excitation resulting in convulsions 1
• Dysphoric reactions and toxic psychoses may occur after any dose 1
• Opioid-induced hyperalgesia (OIH) presents as significant pain escalation and generalized sensitivity to light touch 2
• These CNS symptoms are often caused by accumulation of toxic opioid metabolites, particularly morphine-6-glucuronide (M6G) 2

Cardiovascular Effects

• Hypotension is the major adverse cardiovascular reaction, especially with volume depletion or concurrent vasodilator therapy 2
• Morphine causes venodilation and modest reductions in heart rate through increased vagal tone 2
• High doses cause sympathetic hyperactivity and increased circulatory catecholamines 1
• Hypotension typically responds to supine positioning, IV saline boluses, and atropine when accompanied by bradycardia 2

Other Manifestations

• Nausea and vomiting occur in approximately 20% of patients 2
• Bowel dysfunction including constipation, bloating, incomplete evacuation 2
• Pruritus 2
• Pinpoint pupils (miosis) are a classic sign, though marked mydriasis may occur with hypoxia in overdose situations 1

Special Populations at Higher Risk

Elderly and Frail Patients

• Elderly trauma patients are particularly vulnerable to morphine accumulation with subsequent over-sedation and respiratory depression 2
• Require careful dose titration and close monitoring 2

Renal Failure Patients

• M6G accumulates in renal failure as it is renally excreted, leading to severe intoxication 3
• Morphine dosage must be carefully controlled and reduced in patients with renal impairment 1
• Start with lower doses and titrate slowly while monitoring for side effects 1

Patients with Increased Intracranial Pressure

• Use morphine with extreme caution in head injury or increased ICP 1
• Respiratory depression can elevate cerebrospinal fluid pressure through CO2 retention 1
• Pupillary changes may obscure intracranial pathology 1

Management of Morphine Toxicity

Immediate Interventions

• Naloxone (0.4 to 2.0 mg IV) is the specific antidote for respiratory depression from morphine overdose 2, 1
• Have naloxone and resuscitative equipment immediately available whenever morphine therapy is initiated 1
• Primary attention must be given to reestablishing adequate respiratory exchange through patent airway and assisted/controlled ventilation 1

Naloxone Administration Strategy

• Since naloxone's duration of reversal is shorter than morphine's duration of action, carefully monitor until spontaneous respiration is reliably reestablished 1
• If response is suboptimal or brief, administer additional naloxone as directed 1
• In physically dependent patients, titrate naloxone with smaller than usual doses to avoid precipitating acute withdrawal syndrome 1
• Do not administer naloxone in the absence of clinically significant respiratory or circulatory depression 1

Supportive Care

• Employ oxygen and vasopressors for circulatory shock and pulmonary edema 1
• Cardiac arrest or arrhythmias may require cardiac massage or defibrillation 1
• Hypotension usually responds to supine/Trendelenburg positioning or IV saline boluses 2
• Atropine for bradycardia; pressors rarely required 2

Management of CNS Toxicity

• Opioid dose reduction is the first-line approach for CNS toxicity symptoms 2
• Switching to another opioid agonist and/or another route may improve adverse effects, especially for CNS toxicity like OIH/allodynia and myoclonic jerks 2
• Additional strategies include co-analgesics, nerve blocks, or radiotherapy to achieve opioid reduction 2
• There is little evidence for methylphenidate in managing opioid-induced sedation and cognitive disturbance 2

Management of Other Side Effects

• Metoclopramide and antidopaminergic drugs for nausea/vomiting 2
• Antihistamines and 5-HT3 antagonists for pruritus; opioid rotation is an additional option 2
• Laxative therapy (combination of stool softener and stimulant laxative) should be prescribed prophylactically 2

Critical Pitfalls to Avoid

• Avoid concomitant use with other CNS depressants (benzodiazepines, skeletal muscle relaxants, gabapentinoids) outside highly monitored settings 2
• The combination increases risk of respiratory depression, hypotension, profound sedation, coma, or death 1
• Do not abruptly discontinue morphine after prolonged use; taper gradually to avoid withdrawal syndrome 1
• Be aware that rapid IV administration may cause chest wall rigidity 1
• In elderly patients, particularly those with renal impairment, start with substantially lower doses 2, 1