What is the management approach for a patient with phenobarbitone (barbiturate) poisoning, considering potential complications such as respiratory depression, cardiac arrest, and seizures?

Management of Phenobarbitone (Phenobarbital) Poisoning

For severe phenobarbitone poisoning, immediately initiate aggressive supportive care with airway protection and mechanical ventilation as needed, administer multiple-dose activated charcoal (MDAC) at 15-20 grams every 6 hours after securing the airway, and strongly consider extracorporeal treatment (ECTR) via hemodialysis for patients with prolonged coma, shock after fluid resuscitation, or respiratory depression requiring mechanical ventilation. 1, 2

Immediate Supportive Care (First Priority)

Airway and Respiratory Management:

• Intubate and provide mechanical ventilation for any patient exhibiting respiratory depression, as barbiturates suppress the medullary respiratory center and death commonly results from aspiration pneumonia 1, 2, 3
• Monitor for shallow or Cheyne-Stokes breathing patterns, decreased respiratory minute volume, and development of hypoxia with respiratory acidosis 3
• Patients with chronic obstructive pulmonary disease are at particularly high risk for respiratory depression even at therapeutic doses 1, 2

Cardiovascular Stabilization:

• Administer intravenous fluids aggressively for hypotension and shock, as phenobarbitone depresses medullary vasomotor centers and directly affects myocardium and vascular smooth muscle 3
• Monitor for development of shock syndrome with weak rapid pulse, cold clammy skin, and rising hematocrit 3
• Patients with congestive heart failure are more vulnerable to cardiovascular collapse 1, 2

Continuous Monitoring:

• Track vital signs, CNS status (Glasgow Coma Scale), pulmonary function, and cardiovascular parameters continuously 2
• Obtain serum phenobarbitone concentrations: therapeutic range is 10-25 mg/L, coma occurs >50 mg/L, and potentially fatal levels are >80 mg/L 1, 2
• Check for co-ingestion of other CNS depressants (alcohol, opiates, benzodiazepines) which create additive life-threatening effects 1, 2

Enhanced Elimination: Multiple-Dose Activated Charcoal (MDAC)

MDAC is the cornerstone of enhanced elimination and should be used in ALL significant phenobarbitone poisoning cases 1, 2, 4:

• Administer 15-20 grams orally every 6 hours (initial dose may be 50-100 grams) 2, 4
• Only administer after securing the airway to prevent aspiration 2
• MDAC achieves phenobarbitone clearance of approximately 84 mL/min, which is dramatically superior to endogenous renal clearance of only 1-3 mL/min 1, 4
• Can reduce elimination half-life from 80-120 hours down to approximately 6 hours 1, 4
• Results in 62-93% elimination of absorbed dose within 24 hours 4
• Continue MDAC even during extracorporeal treatment for maximal drug removal 1, 2

Do NOT induce emesis 3

Extracorporeal Treatment (ECTR): For Severe Cases

Indications for ECTR (Strong Recommendations - Level 1D) 1, 2:

ECTR via hemodialysis is strongly recommended when ANY of the following are present:

• Prolonged coma is present or expected 1
• Shock persists after fluid resuscitation 1
• Toxicity persists despite MDAC treatment 1
• Respiratory depression necessitating mechanical ventilation 1
• Serum phenobarbitone concentration rises or remains elevated despite MDAC (weaker recommendation - Level 2D) 1

Choice of ECTR Modality:

• Intermittent hemodialysis is the preferred mode (Level 1D recommendation), achieving phenobarbitone clearance of 23-174 mL/min (up to 188 mL/min with high-flux dialysis) 1
• Hemoperfusion is an acceptable alternative if hemodialysis unavailable (Level 1D), with clearance rates of 26-290 mL/min 1
• Continuous renal replacement therapy (CRRT) is acceptable if other modalities unavailable (Level 3D), though less effective with clearance around 7-9 mL/min 1, 5

Timing and Duration:

• Initiate ECTR as soon as technically possible, ideally within 24 hours of exposure 1
• Continue until clinical improvement is apparent (Level 1D recommendation) 1
• Continue MDAC during ECTR for synergistic drug removal 1, 2

Rationale for ECTR: The EXTRIP Workgroup consensus supports ECTR because: (1) death commonly occurs despite full supportive care alone, (2) no effective antidote exists, (3) ECTR significantly enhances removal compared to endogenous elimination, (4) ECTR reduces duration of coma and complications like pneumonia and kidney failure, and (5) complications from ECTR are infrequent 1

Clinical Assessment Parameters

Serum Levels:

• Obtain serum phenobarbitone concentrations to confirm diagnosis and severity 1, 2
• However, clinical status should guide ECTR decisions, NOT serum levels alone, as concentrations don't reliably predict toxicity duration or severity 1, 2
• Ingested dose estimates are often inaccurate and should not be the sole basis for ECTR decisions 1

Clinical Manifestations to Monitor:

• CNS: sluggishness, incoordination, slow speech, drowsiness progressing to coma; pupils may be constricted initially but show hypoxic dilation late; EEG may show "burst-suppression" pattern 1, 3
• Pulmonary: respiratory depression, atelectasis, pulmonary edema, bronchopneumonia 1, 3
• Cardiovascular: hypotension, compromised cardiac contractility, shock 1, 3
• Other: hypothermia (temperatures as low as 32°C), renal failure 3

Interventions NOT Recommended

• Urinary alkalinization as monotherapy is inferior to MDAC and should not be used as primary therapy 2, 6
• Gastric lavage has limited utility given delayed gastric emptying in barbiturate toxicity and risk of aspiration 1
• Emesis induction is contraindicated 3

Critical Pitfalls to Avoid

• Do not delay intubation in patients with altered mental status, as aspiration pneumonia is a leading cause of death 1, 3
• Do not withhold ECTR based solely on serum levels - clinical deterioration with shock or prolonged coma mandates ECTR regardless of concentration 1
• Do not administer MDAC without airway protection in obtunded patients 2
• Be aware that chronic phenobarbitone users develop tolerance to sedative effects but NOT to lethal respiratory depression, and rapid removal via ECTR may precipitate withdrawal 1
• Do not use ECTR for short-acting barbiturates (pentobarbital) as they have larger volumes of distribution and ECTR is minimally effective 1