Porphyric Crisis

Porphyric Crisis (Acute Neurovisceral Crisis) 

Background: 

-The porphyrias are caused by enzyme deficiencies in the heme production pathway. Such deficiencies may be due to inborn errors of metabolism or exposure to environmental toxins or infectious agents.

-The disease was named porphyria due to the red discoloration of urine in affected patients, (figure 1).

-Crises are four to five times more common in women and usually occur in their early 30s.

Figure 1: Porphyria Red Urine

Triggering factors: 

Enzyme-inducing drugs: 

-Barbiturates (Thiopental, Methohexital), Etomidate, Enflurane, Alcuronium, Mepivacaine, Pentazocine, Nifedipine, Verapamil, Diltiazem, Phenytoin, Hydralazine, Phenoxybenzamine, Aminophylline 

Physiological: 

-Menstruation, Fasting, Dehydration, Stress, Infection, Anemia, Endogenous hormones 

Habits: 

-Smoking, Alcohol 

Clinical Picture: 

CNS: 

-Autonomic neuropathy (Fever, Pain, Constipation, Gastroparesis, Postural hypotension) 

-Peripheral neuropathy (Skeletal muscle weakness, Quadriparesis, Bulbar palsy, Respiratory failure) 

-Cranial nerve palsy 

-Seizures 

-Psychiatric features (Mood disturbance, Confusion, Psychosis) 

CVS: 

-Tachycardia, Hypertension 

GIT: 

Acute abdominal pain, Vomiting, Diarrhea, Dehydration, Electrolyte disturbance (↓ [Na⁺, K⁺, Mg⁺²]) 

Management: 

Remove triggering factors (above) 

Specific R: 

-Hematin, Heme arginate / Heme albumin, Somatostatin, Plasmapheresis 

Symptomatic R: 

-Pain: Substantial doses of Opioids 

-Nausea and Vomiting: Prochlorperazine, Ondansetron 

-Anxiety: Lorazepam, Midazolam in low doses 

-Insomnia: Zopiclone 

-Delirium: Haloperidol 

-Tachycardia & Hypertension: β-adrenergic blocking agents, Glyceryl trinitrate 

-Seizures: Benzodiazepines, Levetiracetam, Clonazepam, Gabapentin, Vigabatrin, Magnesium sulphate 

-Sedation: Propofol, Alfentanil infusions. The clinical safety of prolonged midazolam infusion is unknown. 

-Thromboembolic prophylaxis: LMW heparins 

-Stress ulcer prevention: IV Omeprazole, Ranitidine 

-Correction of electrolytes

Mechanical Ventilation for Respiratory failure

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Carcinoid Crisis

Carcinoid Crisis

Definition:

-Carcinoid crisis is the most serious and life-threatening complication of carcinoid syndrome and is generally found in people who already have carcinoid syndrome.

-Carcinoid crisis occurs when all of the symptoms of carcinoid syndrome come at the same time. 

Causes:

➧ Spontaneous 

➧ Precipitating factors: 

-Stress, Sympathetic stimulation 

-Hypotension 

-Histamine releasing drugs 

-Tumour manipulation 

-Regional anesthesia due to hypotension 

-Infection 

-Chemotherapy 

Clinical picture:

-Tachycardia, Arrhythmia 

-Hypotension, Shock 

-Flushing, Hyperthermia 

-Bronchospasm 

-Abdominal pain, Diarrhea 

Management:

Inhibit growth h. & vasoactive peptides release:

-Somatostatin analogs (Octreotide, Lanreotide) 

Anti-serotonin:

-Methesergide, Ketanserin, Cyproheptadine, Ondansetron, Alpha-methyl dopa 

Anti-kallikrein:

-Corticosteroids, Aprotinin

Anti-histamine:

-H1 blockers (Diphenhydramine) & H2 blockers (Ranitidine) 

R of Bronchospasm:

-Salbutamol, Aminophylline 

R of Diarrhea:

-Loperamide 

R of Hypotension:

-Vasopressin, Phenylephrine 

R of Hypertension:

-Alpha-blockers, Beta-blockers 

R of Rt. Heart failure:

-Digitalis, Diuretics

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Sodium Nitroprusside Toxicity

Sodium Nitroprusside Toxicity:

Mechanism of Action:

After parenteral injection, sodium nitroprusside enters red blood cells, where it receives an electron from the iron (Fe⁺²) of oxyhemoglobin. This non-enzymatic electron transfer results in unstable nitroprusside radical and methemoglobin (Hb Fe⁺³). The former moiety spontaneously decomposes into five cyanide ions and the active nitroso (NO) group. 

The cyanide ions can be involved in one of three possible reactions: 

1) Binding to methemoglobin to form cyan-methemoglobin.

2) Undergoing a reaction in the liver and kidney catalyzed by rhodanase enzyme to form thiocyanate + thiosulfate.

3) Binding to tissue cytochrome oxidase, which interferes with normal oxygen utilization.

N.B. Sodium nitroprusside toxicity is usually related to prolonged administration or occurs in patients with renal or hepatic failure. 

Mechanisms of Toxicity:

1) Direct vasodilation: resulting in hypotension and dysrhythmias (most common).

2) Thiocyanate toxicity: (occurs infrequently).

3) Cyanide toxicity: (in rare cases).

4) Methemoglobinemia: (in very rare cases).

Thiocyanate toxicity :

Symptoms:

Anorexia, nausea, abdominal pain, fatigue, and mental status changes, including psychosis, weakness, seizures, tinnitus, and hyperreflexia. 

Treatment: 

-Toxicity can be minimized by avoiding prolonged administration of nitroprusside and by limiting drug use in patients with renal insufficiency (as thiocyanate is usually excreted in the urine). 

-Thiocyanate can be removed by dialysis (if necessary). 

Cyanide toxicity:

-An early sign of cyanide toxicity is the acute resistance to the hypotensive effects of increasing doses of sodium nitroprusside (tachyphylaxis). (It should be noted that tachyphylaxis implies acute tolerance to the drug following multiple rapid injections, as opposed to tolerance, which is caused by more chronic exposure). 

-Acute cyanide toxicity occurs when the cyanide ions bind to tissue cytochrome oxidase and interfere with normal oxygen utilization. This leads to metabolic acidosis, cardiac arrhythmias, and increased venous oxygen content (as a result of the inability to utilize oxygen). 

Symptoms: 

-Cyanide toxicity is often associated with the odor of almonds on breath and can result in metabolic acidosis, tachycardia, mental status changes, respiratory arrest, coma, and death. 

Treatment: 

-Cyanide toxicity can usually be avoided if the cumulative dose of sodium nitroprusside is less than 0.5 mg/kg/h. 

-Mechanical ventilation with 100% oxygen to maximize oxygen availability. 

-Administering sodium thiosulfate (150 mg/kg over 15 min) or 3% sodium nitrate (5 mg/kg over 5 min), which oxidizes hemoglobin to methemoglobin, or by limiting the administration of nitroprusside. 

Methemoglobinemia:

-Methemoglobinemia occurs due to excessive doses of sodium nitroprusside or sodium nitrate, if the level is greater than 15 %, it can result in symptomatic cellular hypoxia.

Treatment: 

-Methylene blue (1–2 mg/kg of a 1% solution over 5 min), which reduces methemoglobin to hemoglobin.

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