A Case of Altered Mental Status

History of Present Illness:

A 64-year-old female presents to the Emergency Department by Emergency Medical Services for altered mental status and shallow breathing.  EMS provided supportive care en route.  The patient was unable to provide any history for herself.  EMS states that the “patient's roommate” activated the 911 system.  EMS has a limited history for the patient.

1. What else would you ask EMS before they leave?

The patient’s daughter arrived shortly after patient arrival in the ED.  She states that she last talked to the patient on Friday and she was "completely normal."  Patient’s daughter does not know who the PMD is and states she has history of “psychiatric issues” and pre-diabetes.

Initial Vitals:

1145 hrs:  94 bpm, 28 resp, 148/78 mmHg, 94% on 15L NRB

2. Are there any other vital signs you could've obtained?

Primary Examination:

The patient's physical examination is significant for her being in moderate distress and ill-appearing. She is not maintaining her airway and she has shallow rhonchorous breath sounds bilaterally, right greater than left.  Her pulses are equal and with a rate of 95.  Her heart sounds are regular.  Her abdomen is soft, non rigid, without guarding.  Her extremities are normal without signs of trauma or ecchymoses.  Her pupils are 3 mm, sluggishly reactive.  Her skin is warm and dry.  Her neurologic examination is severely limited.  Her eyes are open and she localizes to pain, but does not answer any questions or follow command.

3. What other physical exam findings would be pertinent for this patient?

Resuscitation:

Patient had two 18g peripheral lines placed and bloods were drawn for lab tests.  Patient was given RSI with 20mg of Etomidate and 100mg Succinylcholine, subsequently intubated with direct laryngoscopy.  Foley catheter with temperature probe was placed to show a core temperature of 94.3F.  IVF boluses were ordered 0.9% NS 1 liter.  The patient was sedated for the ventilator with Propofol.

4. What are the initial vent settings for this 65-kg patient and why?

Diagnostic Interventions:

1206 hrs: Initial ABG

pH pCO2 pO2 HCO3 Lactate SpO2 BE Na K
7.05 47 317 13 6.7 100% -17 145 3.8

 

1232 hrs: CBC, CMP, Cardiac Enzymes, UA

WBC Hgb Hct Plt RDW Bands MCV MCH
4.1 13.7 42 114 14 1 90.7 29.6

 

Na K Cl HCO3 BUN Cr Glu GFR
145 4.3 103 13 49 4.28 265 11

 

Ca Alb T.Pro T.Bili ALT AST Alk Phos
6.1 3.2 5.8 0.4 16 47 45

 

CPK CKMB Troponin
696 30.1 <0.06

 

pH SpGr LE Nitrites Urobil Prot Glu Blood Ket
6.0 1.020 NEG NEG 0.2 100 100 MOD NEG

 

1300 hrs: Chest radiography shows a right-sided infiltrate.

5. What is the reaction and intervention to the ABG?

6. What are your next interventions after seeing the portable CXR?

7. What are you next interventions after seeing the CMP?

1320 hrs: Computed tomography of the head is unremarkable.

1327 hrs: EKG is as demonstrated below.

8. Are there any interventions to take regarding the EKG results?

Therapeutic Interventions:

1340 hrs: 3L bolus of Lactated Ringers ordered for patient.
Ceftriaxone and Azithromycin were ordered for the patient according to the CAP algorithm.

1450 hrs: Magnesium 2g given IVPB.

Reassessment, Additional HPI:

1502 hrs: Repeat VBG following IVF and Abx

pH pCO2 pO2 HCO3 Lactate SpO2 BE Na K
7.03 51 53 13.5 6.3   -17.1 143 4.5

 

1552 hrs: T 95.2 (foley), 77 bpm, 22 resp (ventilated), 114/68 O2 95%
Bair hugger was placed on patient to warm her.

1636 hrs: Repeat ABG

pH pCO2 pO2 HCO3 Lactate SpO2 BE Na K
7.07 48 63 13.9 4.2 80 -15.8 143 4.1

 

Patient has no source of infection or ischemia at this time.  The lactate remains elevated, with no signs of shock, despite aggressive IVF management.  Patient is in renal failure and there was no past history of renal failure. There were no labs for comparison.  Pulmonary consult was contacted and the patient was approved for ICU at 1619 hrs.  She was admitted shortly thereafter and continued to slowly improve.

9. What is the diagnosis?  Was something missing? Would you have done anything differently?

10. Now what?

Pathophysiology of Valproic Acid (VPA) Overdose:

  1. VPA decreases inter-mitochondrial carnitine stores.  This occurs through inhibition of the carnitine transporter, which brings carnitine into the cell.
  2. VPA traps mitochondrial CoA.  Acyl carnitine is depleted and β-oxidation is inhibited, which causes decreased ATP production.  ATP production is a dependent on carnitine transporter function.
  3. Carnitine depletion.  Impaired transport of Long Chain Fatty Acids across the inter-mitochondrial membrane interrupts β-oxidation. Accumulation of toxic by-products interrupts Krebs, Urea and Cori cycles.  Ammonia levels rise in relation to metabolic derangement.
  4. Omega-oxidation. Interruption of β-oxidation causes ω-oxidation to occur, causes formation of 4-EN-VPA, a suspected hematotoxin.

Clinical Findings and Diagnostics:

  • Physical Signs & Symptoms:
    • Neuro: AMS, from lethargy to coma.  Nystagmus, ataxia, tremor not always seen.  Neurotoxicity worse in acute-on-chronic cases.
    • GI: pancreatitis, GI distress, anorexia.

  • Metabolic Derangements:

    • Hypernatremia, hypocalcemia early.  
    • Hypocarnitinemia, hyperammonemia and metabolic acidodis occurs as the overdose continues.
    • Hyperammonemia (> 80 mcg/dL) is seen in 16-52% of chronic VPA users, also seen in acute-on-chronic overdoses (our patient).  Acute OD not common to have elevation in ammonia.
    • Metabolic acidosis and elevated lactate levels seen in massive overdose and have a poor prognosis. 

  • Bone Marrow suppression: seen 3-5 days out in massive oversdoses.  Pancytopenia should resolve spontaneously in a few days.
  • Hepatotoxicity:

    • Aminotranferases transiently elevate and are dose-dependent.  Hepatitis responds to carnitine replenishment
    • May see a Reye’s-like syndrome

  • Diagnosis:

    • VPA level > 50-100 mg/L
    • Serum ammonia level

Treatment:

  • Supportive care is usually all that is needed.
  • Resuscitate as any other patient.
  • Consider GI Decontamination with whole-bowel irrigation for enteric coated or extended release formulations. Multi-dose activated charcoal (MDAC) can be considered if the ingestion is known.
  • Carnitine is recommended if there is evidence of hyperammonemia or hepatotoxicity.

The loading dose is 100 mg/kg IV over 30 minutes followed by 15 mg/kg over 10-30 minutes q4h. 

  • The AAP recommends its use for children < 2 years or with chronic neuromuscular disorders, ketogenic diets.
  • Hemodialysis is an option but generally not required

Reference:

Goldfrank’s Manual of Toxicologic Emergencies .  2007. Chapter 47 Anticonvulsants. P 403-413.