Senior Report 7.2

Case Presentation by Dr. Andrew Klutman

CC: 73 yo male brought in by EMS for confusion and difficulty in breathing

HPI: According to EMS, up until yesterday the patient was his normal self other than his worsening chronic back pain. He woke up and simply did not feel well. As the day progressed he became more tired and slept most of the day. In the middle of the night, the patient had trouble sleeping. He started developing a cough and began running a slight fever. His wife woke found him sleeping in the recliner this morning. She attempted to wake him up but had difficulty arousing him which is when she called EMS. Upon arrival the patient’s saturations were in the high 80’s so EMS placed him on a non-rebreather. The patient is unable to provide any history

ROS: Unable to obtain due to clinical condition

PMH: CAD – NSTEMI, HTN, DM, COPD and chronic back pain
Surgical Hx: Hernia repair, right knee replacement 3 years ago
Allergies: None
Medications: Insulin, metformin, carvedilol, aspirin
Social: 20+ pack year history for tobacco, occasional alcohol and no illicit drugs

Physical Exam:
Vitals: T 38.2 HR 125 BP 130/86 RR 20 Sats 96% on a non-rebreather
General: Patient is drowsy but will open his eyes to stimulation
Eyes: Eyes are non-icteric, non-injected, pupils are round, equal and reactive to light
HENT: Head is normal cephalic, atraumatic. Neck is supple without nuchal rigidity. Patient does have a gag reflex. No JVD
CV: Tachycardic but regular rhythm. No murmurs. Palpable pulses in his upper and lower extremities
RESP: Diffuse crackles. Patients respirations are deep and slightly tachypnic.
Abdomen: Soft, non-distended, no obvious tenderness to palpations. Fecal occult negative, good rectal tone.
Extremities: Though he does not follow commands he does move all extremities spontaneously.
Skin: Warm to touch but no obviously rashes or lesions.
Neuro: Patient will not follow commands but does move extremities spontaneously. He does speak some words you can understand but do not make sense. He opens his eyes spontaneously. His eyes are noted to move past midline. No clonus.

Labs:

Electrolytes: Na-132 K-3.1 Cl-92 CO2-14 BUN-60 Cr-2.1 Glu-310

CBC: WBC-18 HGB-9.9 PLT-199 HCT-100

INR: 1.73 PT:

Lactate: 4.1

Troponin: .489

VBG: pH-7.29 pCO2-19.7

TSH: 1.734

ECG:

Chest XR:

Head CT:

1. What is the correct interpretation of the patient’s acid-base status
a. Acute respiratory acidosis and chronic metabolic alkalosis
b. Chronic metabolic acidosis and acute respiratory alkalosis
c. Acute metabolic acidosis with incomplete respiratory compensation
d. Acute respiratory acidosis with incomplete metabolic compensation

2. What do you feel is the most likely diagnosis
a. NSTEMI
b. CVA
c. CHF
d. Salicylate toxicity

3. How would you treat this patient’s underlying problem?
a. Initiate heparin for an NSTEMI
b. Stroke consult – consider TPA
c. Early goal directed therapy
d. Serum/urine alkalization with NaCO3

Bonus Question (academic purposes only)

Would you intubate this patient, why, why not and any special concerns?

Answers and Discussion

1) B – its the only one with a mixed metabolic acidosis and respiratory alkalosis
2) D
3) D – Initiate alkalization in order to minimize CNS toxicity

Question 1. Typically when considering salicylate toxicity most of us know to look for an acute respiratory alkalosis characteristic of salicylate toxicity. The mechanism of action is stimulation of the CNS respiratory center causing hyperpnea (rapid, deep breaths) ultimately leading to a fall in pCO2 and a respiratory alkalosis. This respiratory alkalosis predominates in the early stages, usually within 24 hours, of salicylate toxicity. Later stages of severe salicylate toxicity is characterized by accumulation of organic acids, mainly lactic acid and ketones, causing a metabolic acidosis as well. Salicylates drive the metabolic acidosis by uncoupling oxidative phosphorylation leading to increased energy production and utilization within the cells causing increased dependence upon an anaerobic metabolism. In this case, the patient’s lactate was elevated above 4 and if a UA was obtained it would likely show ketones. The interesting aspect of salicylate toxicity is that there are no “givens.” Just because there is not an anion gap does not mean that it is not the underlying cause. Depending upon when the patient presents in their toxicity course will determine what acid/base disorder you may see. Therefore, you can have any combination of acid-base discrepancies. Depending on timing, level of toxicity, co-ingestions and underlying co-morbidities you may not appreciate a respiratory alkalosis which is seen early but not necessarily late in their toxicity. However, looking at this patient we have:

Electrolytes: Na-132 K-3.1 Cl-92 CO2-14 BUN-60 Cr-2.1 Glu-310

VBG: pH-7.29 pCO2-19.7

The first step is to decide if this is acidosis or alkalosis. So obviously this is an acidosis as the pH is less than 7.38. Step 2 is deciding the primary process. Here we have a low HCO3 and CO2 so this a metabolic acidosis. Next is to access compensation. As we decided that this is a primary metabolic acidosis we can use Winter’s formula; PCO2=1.5(HCO3) + 8 (+/- 2). Applying the formula we expect a PCO2 of 27-31. As his pCO2 is below that value, the patient has a metabolic acidosis along with a primary respiratory alkalosis.

Question 2. The reason I chose this case is because in my 2 years and 7 months of residency I have developed new appreciation for the power of the endocrine system, influenza and now aspirin. Bottom-line, aspirin may improve mortality in an MI but it can cause some serious problems. Looking at this patient his aspirin toxicity could easily have been mistaken for heart failure, dementia, sepsis, MI and DKA. Unfortunately chronic aspirin toxicity frequently has a delayed diagnosis due to it’s similarities to the diagnosis listed above. Instead, it is often diagnosed days after admission when the ICU consults Dr. Hedge or Dr. King. Think about it, how many times have you honestly considered aspirin toxicity in an elderly patient, on aspirin, with mental status changes. Unless you are Craig Sharkey, I would be willing to bet rarely.

So how can you make the diagnosis? Early symptoms include tinnitus, vertigo, nausea, vomiting and diarrhea. But how often are ED Doc’s privileged to early symptoms? As discussed above, most clinicians “hang their hats” on a respiratory alkalosis. But what about a patient with COPD or other chronic CO2 trappers? Could this patient have a normal pCO2 and HCO3 and still be in physiological respiratory alkalosis? I feel that he most definitely could have but as most of us realize, there definitely would be some ethical problems conducting toxic substance ingestion randomized controlled trials in humans to prove this. So, what else can we look for?

The SDS provides great incite. Generally salicylate levels above 40mg/dL are considered toxic. Salicylate levels should be obtained every 2 hours in patients until 2 consecutive levels show a downward trend below 40 and the patient is asymptomatic with a normal respiratory rate. Levels may not begin to rise until 5-6 hours after ingestion due to pylorospasm, bezoar formation or enteric coated pills. Also of note, 10-30 g of acute aspirin ingestion for adults and 3g for children is usually considered fatal. Chronic ingestion and toxicity is harder to quantify. My point was to illustrate that in this patient a therapeutic aspirin level should at least perk your interest for possible chronic toxicity.

Vital signs are frequently not useful in suspecting ASA toxicity either. Do not let vital signs talk you out of aspirin toxicity. Low grade fevers are common. This may occur due to ASA uncoupling oxidative phosphorylation in mitochondria. The uncoupling causes generation of heat ultimately leading to fever. Toxic aspirin patients typically present with hyperpnea as well. These patients take deep, rapid breaths so paying attention to their breathing can be pivotal. Along the same lines, tachycardia is frequently present. These patients can be agitated, dehydrated due to vomiting/diarrhea and increased osmotic diuresis, and in general distress.

Though not always necessary, imaging can help in completing the diagnosis. This patient has an chest x-ray showing non-cardiogenic pulmonary edema. This can be very subtle on x-ray or very prominent as in this case. The edema is most likely related to increased membrane permeability and acidosis. The patient also had a head CT that showed cerebral edema. The progressive acidemia facilitates the ability of salicylic acid to cross the blood brain barrier leading to cerebral edema again likely through increased membrane permeability.

Finally, salicylate toxicity can also cause thrombocytopenia.

Question 3. As with all resuscitations of critically ill patients, we follow the ABC’s upon presentation. The exception is intubation as it should only be reserved for patients with obvious respiratory failure or impending collapse. Even the brief apnea during RSI is enough to worsen the patients acidosis causing the protonation of anions to salicylic acid allowing them to cross the BBB and worsening the patients CNS toxicity. Once intubated, the acidosis is exacerbated with ventilator asynchrony and relative ventilator related hypoventilation. If you must intubate these patients, shoot for tidal values in the 6-8 mL/kg and high ventilation rates. Also avoid deep sedation or long acting paralytics which blunt the patients ability to breath over the vent. You need to match the patient’s own minute ventilation if you intubate them. If you do not, their Co2 will rise and worsen their acidosis which can be fatal.

The base-line treatment of salicylate toxicity is sodium bicarb. The goal is to first correct the CNS acidosis and decreased the BBB permeability to salicylic acid. It is theorized that it’s the CNS toxicity that kills these patients. The secondary affects of bicarb is alkalization of the urine facilitating aspirin excretion. The initial dose of bicarb is 1-2 mEq/kg IV bolus. Then you should start the patient on a bicarb infusion of 100-150 mEq in D5. This is made by placing 3 amps of NaHCO3 in a liter of D5water. The rate is titrated to a urine pH of 7.5-8 which commonly comes out to 1.5-2 times maintenance. Hypokalemia also needs to be corrected to facilitate urine alkalinization. You also need to check serum pH frequently to be sure you are not over alkalinizing them. Your target serum pH is 7.45-7.5. These patients will need a foley to monitor urine output, check Q1H urine pHs until your target is reached. It is also imperative that you know they are making urine. Place a arterial line for frequent blood draws and blood pressure monitoring.

In our patient, he has altered mental status which is likely due to the CNS toxicity and edema, but also neurohypoglycopenia (decreased cerebral glucose). In animal models, it has been demonstrated that even if the patient is normoglycemic or even hyperglycemic, they have low CNS glucose. As expected, no studies have been conducted on humans but the recommendation is to maintain a normal glucose level of 80-120 or even slightly higher.

The big question here is when do we perform hemodialysis. The serum salicylate hard number is > 100 mg/dL. Talking with the Toxicologist, much of it depends on the clinical picture. For instance, our patient has a rather poor clinical picture. He has renal failure, altered mental status, pulmonary and cerebral edema which each alone is an indication for dialysis. Pulmonary edema greatly complicates fluid resusitation and bicarb therapy. Renal failure hinders bicarb therapy and aspirin secretion. And as discussed above, altered mental status and cerebral edema carries an extremely high mortality. So be rather aggressive in patients with the above findings or those who mental status are not improving with conventional treatment. Lastly, contact your toxicologist regarding activated charcoal.

Key Points: