Case Presentation by Dr. Jessie Swan, MD
History of Present Illness:
A 62-year-old African American male was brought to the Emergency Department by EMS after being found lying on the ground inside an abandoned house. His friends had called EMS because he had been lying in the same spot for the past three days. Per EMS there were no pill bottles or alcohol bottles around the patient. The outdoor temperature was in the 20s and EMS states that the house was not heated; actually it felt colder inside the building than outdoors. You were unable to obtain any other history from the patient as he is only able to mumble incoherently.
Past Medical History (per EMR):
Social history (per EMR):
-Denied tobacco, alcohol or other drugs
Medication (per EMR):
-Norvasc 5mg daily
Vitals: BP 94/64, P 67, RR 14, T 28.4 °Celsius rectal, oxygen saturation unable to obtain.
GENERAL: He is lying in bed and appeared disheveled. Dressed in only one layer of long underwear under jeans and a jacket. He mumbled incoherently in response to stimuli.
HEAD: Without evidence of trauma.
EYES: Pupils are 3 mm, round and nonreactive to light bilaterally.
EARS, NOSE, MOUTH, AND THROAT: Throat was clear. Mucous membranes appear to be dry.
NECK: Trachea midline.
RESPIRATORY: Lungs revealed clear breath sounds bilaterally.
CARDIOVASCULAR: The patient had a heart rate of 67 beats/minute and rhythm was regular. He had faint palpable pulses in his wrist and feet bilaterally.
GASTROINTESTINAL: Abdomen is soft, nondistended, nontender to palpation. No palpable masses.
EXTREMITIES: No edema. He had cyanosis of his feet bilaterally.
SKIN: Extremely cold to the touch without evidence of skin rash. He had some previous signs of skin grafting and scarring in his right upper chest wall.
NEUROLOGIC: He had spontaneous eye opening. He did appear to follow some simple commands, He could not provide any further information. Patient was not flaccid however was weak in the upper and lower extremities. Localized to painful stimuli.
Labs / Imaging / ED course:
Na 132, K 3.8, Cl 86, Bicarb 5, BUN 58, Cr 3.09, Glucose 74, Anion gap 41
WBC 7.3, Hgb 13.5, Platelet 186, MCV 96.3
CPK 3932, Lactic Acid 10.9, Trop 0.247, EtOH 283
ABG: pH 6.84, PCO2 19.0, PO2 6.9, HCO3 2.0
CXR: Patchy multifocal airspace opacities noted bilaterally concerning for multifocal pneumonia and/or aspiration pneumonia.
The patient was covered with warm blankets and fluid resuscitated with a total of warmed 3L 0.9% NS. A femoral central line was placed using a Zoll triple-lumen central line femoral vein catheter and central rewarming was initiated. Patient was also started on Azithromycin and Ceftriaxone, given 2 Amps NaHCO3, and given a rectal aspirin. He was admitted to the MICU.
1. What is the acid/base disturbance?
a. Primary: non anion gap metabolic acidosis. Secondary: respiratory alkalosis
b. Primary: anion gap metabolic acidosis. Secondary: respiratory acidosis
c. Primary: anion gap metabolic acidosis. Secondary: respiratory alkalosis
d. Primary: non anion gap metabolic acidosis. Secondary: respiratory acidosis.
2. All of the following are common physiologic EKG findings associated with hypothermia EXCEPT?
b. Atrial fibrillation
c. J waves
d. Ventricular fibrillation
3. Under what circumstance is further intervention generally considered futile?
a. A potassium level >12mmol/L
b. After 2 hours of CPR
c. When the patient presents initially without signs of life and absent vital signs.
d. When, after rescue and initial intervention, the patient’s core temperature continues to drop.
Answers & Discussion:
Primary metabolic acidosis, with increased anion gap, mixed with a metabolic alkalosis, with superimposed respiratory acidosis
First: pH is 6.84 which is an acidosis
Second: pCO2 is low at 19, Bicarb is low at 2.0 so this is a primary metabolic acidosis
Third: Winters Formula PCO2=1.5(HCO3)+8±2; PCO2=9to13; actual CO2 is higher at 19 so there is a secondary respiratory acidosis
Fourth: Anion Gap=Na-(Cl+HCO3); Anion Gap=41; the anion gap is >12 so this is an anion gap metabolic acidosis
EXTRA: Fifth: Delta Gap=(AG-12)-(24-HCO3); Delta Gap=10; the delta gap is >6 so this represents an anion gap metabolic acidosis with a mixed metabolic alkalosis.
A. At a core temperature of 28 degrees Celsius oxygen consumption and the pulse rate are usually decreased by 50%.
B. Atrial fibrillation is common when the core temperature is less than 32 degrees Celsius and is generally not worrisome in the absence of other signs of cardiac instability. It rarely leads to a ventricular response.
C. J waves (Osborne waves) appear secondary to an exaggerated outward potassium current leading to a repolarization abnormality. These waves are detectable in 80% of the patients with a core body temperature lower than 30°C. J waves are seen in lead II and precordial leads V2-V6.
D. Ventricular findings are serious when seen in hypothermic patients. Ventricular arrhythmias are very difficult to correct in these patients and often result in asystole.
A. A severely elevated serum potassium level is associated with nonsurvival. It is an indication of hypoxia before cooling. If the serum potassium level is higher than 12mmol/L termination of CPR should be considered. The highest recorded levels of serum potassium in patients with hypothermia who were successfully resuscitated are 11.8 in children and 7.9 in adults. At a level between 10 and 12 it is recommended that consideration of ECMO or CPB should be made. A level below 10 should prompt continued CPR until the patient is rewarmed as survival without neurologic impairment may be possible
B. The longest reported duration of CPR in a hypothermic patient who subsequently achieved full neurologic recovery is 190 minutes in a patient receiving extracorporeal rewarming.
C. Stage HT IV of the Swiss staging system is characterized by a core temperature of <24ºC with no vital signs. In these patients appropriate treatment includes active external and minimally invasive rewarming techniques, airway management as required, ECMO or CPB if cardiac instability is refractory to medical management, plus CPR with up to three doses of epinephrine and defibrillation with further dosing guided by clinical response.
D. A drop in temperature, indicating continued core cooling after rescue, is a documented phenomena. This may also be the result of discrepancies between different methods of temperature measurement.
Case Presentation by Dr. Joe Wollman, MD
History of Present Illness:
A 71-year-old Caucasian woman is brought to the emergency department from a long-term health care facility with altered mental status. The patient was reported to be agitated and combative with nursing staff at the care facility. At her baseline the patient is alert and oriented x2, and is able to perform some of her Basic Activities of Daily Living (including feeding and functional mobility) but now appears confused and has been unable to respond appropriately to questions and commands.
Past Medical History (per EMS report):
Vitals: BP 79/36, P 123, RR 25, T 38.4, O2 sat 95% room air, Wt 52 kg.
General: Lethargic elderly woman appears agitated when disturbed.
HEENT: Normocephalic, atraumatic. Anicteric sclera. No conjunctival injection, but pallor present. Tympanic membranes non-bulging, non-erythematous. Edentulous with dry mucus membranes. No posterior oropharyngeal exudates. No lymphadenopathy.
Cardiovascular: No JVD. Regular rhythm, no murmurs, and no peripheral edema.
Respiratory: Coarse breath sounds with rhonchi auscultated over bilateral anterior lung fields, no rales or wheezes.
Gastrointestinal: Abdominal is soft, non-distended.
Musculoskeletal: Extremities warm to touch with brisk capillary refill.
Genitourinary: Foley catheter in place draining dark yellow urine.
Neurologic: GCS 11 (opens eyes to voice, inappropriate words, localizes to painful stimuli). Extra ocular movements intact. Pupils 5 mm and equally reactive to light.
Labs / Imaging / ED course:
Blood sugar is 110. WBC is 15,000 with 68% neutrophils, 3% bands, and 23% lymphocytes.
Urinalysis shows 3+ leukocyte esterase, nitrite negative, trace blood, 50 WBC and 3 RBC per HPF with many bacteria present.
Chest x-ray shows poor inspiratory effort with slight enlargement of the cardiac silhouette, but no signs of pulmonary edema, and no focal consolidations.
The patient receives bolus IV fluids (2 liters) with repeat blood pressure measured as 88/55. Arterial blood gas reveals a pH of 7.21, and a lactic acid of 9 mmol/L.
1. Please select the most accurate statement:
a. Infection is the primary cause of death in approximately two-thirds (66%) of individuals aged 65 years and older.
b. Urinary tract infection is second only to respiratory tract infection as the most common site of infection in nursing homes.
c. Less than one-third (33%) of patients with an indwelling catheter and bacteriuria develop UTI symptoms.
d. Systemic antimicrobials are recommended to prevent catheter associated urinary tract infections in patients requiring long-term catheterization.
2. In patients with septic shock, the strongest predictor of survival/mortality is:
a. Whether or not initial antimicrobial therapy has appropriate coverage.
b. Time to initiation of antimicrobial therapy with appropriate coverage.
c. APACHE II score at ICU admission.
d. Time to initiation of vasopressor/inotropic support.
e. Volume of fluids infused in the first hour of hypotension.
3. Regarding fluid resuscitation of patients with severe sepsis and septic shock, which statement is most accurate?
a. Mortality rates are lower in patients who receive crystalloid solution verses patients who receive albumin solution.
b. There is no statistically significant difference in mortality rates in patients who receive hydroxyethyl starch or pentastarch verses patients who receive crystalloid.
c. Liberal fluid resuscitation has not been shown to prolong duration of mechanical ventilation even if Acute Respiratory Distress Syndrome develops.
d. Mechanically ventilated patients require higher Central Venous Pressures for resuscitation.
Answers & Discussion
The clinical significance of asymptomatic bacteriuria in catheterized patients is uncertain. Only 10 to 25% of those with bacteriuria develop symptoms of UTI (1, 2, 3). Infection is the primary cause of death in approximately one third (33%) of individuals aged 65 and older (4). Urinary tract infections are the most common site of infection in nursing homes (5). The CDC recommends against the routine use of systemic antimicrobials to prevent catheter associated urinary tract infections in patients requiring either short or long-term catheterization (6).
In a retrospective cohort study performed by Kumar and Wood between 1989 and 2004, with the objective to determine the prevalence and impact on mortality of delays in initiation of effective antimicrobial therapy from initial onset of recurrent/persistent hypotension of septic shock, multivariate analysis (including APACHE II score and multiple therapeutic variables), time to initiation of effective antimicrobial therapy was the single strongest predictor of outcome (7).
Mechanically ventilated patients may require higher CVP targets (i.e. 12-15 mmHg rather than 8-12) to account for impediments in filling (8). The SAFE trial (an RTC involving 6997 critically ill patients) showed no differences in mortality between resuscitation with crystalloid verses albumin (9). Scandinavian Starch for Severe Sepsis and Septic Shock trial (an RTC involving 804 patients) showed increased mortality at 90 days with hydroxyethyl starch verses crystalloid (10). The VISEP trial, designed compare pentastarch to crystalloid was stopped due to trend toward increased 90-day mortality with pentastarch (11). In patients with ARDS who are hemodynamically resuscitated, a liberal approach to IV fluid administration prolongs duration of mechanical ventilation (12).
1. Catheter-associated urinary tract infection is rarely symptomatic: a prospective study of 1,497 catheterized patients. Tambyah PA, Maki DG Arch Intern Med. 2000;160(5):678.
2. Clinical and economic consequences of nosocomial catheter-related bacteriuria. Saint S. Am J Infect Control. 2000;28(1):68.
3. Complications of Foley catheters–is infection the greatest risk? Leuck AM, Wright D, Ellingson L, Kraemer L, Kuskowski MA, Johnson JR. J Urol. 2012 May;187(5):1662-6.
4. Common infections in older adults. Mouton CP, Bazaldua OV, Pierce B, Espino DV. Am Fam Physician. 2001;63(2):257.
5. Important sites and pathogens causing infections in long-term care facilities. Richards M, Stuart R, Up to Date. 2013.
6. CAUTI guidelines 2009 – Category IB recommendation.
7. Duration of hypotension before initiation of effective antimicrobial therapy is the critical determinant of survival in human septic shock. Kumar A, Roberts D. Crit Care Med. 2006;34(6):1589.
8. Surviving Sepsis Campaign. Dellinger RP, Levy MM, Rhodes A. Critical Care Medicine. 2/2013;41(2):580–637.
9. A comparison of albumin and saline for fluid resuscitation in the intensive care unit. Finfer S, Bellomo R. N Engl J Med. 2004;350(22):2247.
10. Hydroxyethyl starch 130/0.42 versus Ringer’s acetate in severe sepsis. Perner A, Haase N, Guttormsen AB. N Engl J Med. 2012;367(2):124.
11. Intensive insulin therapy and pentastarch resuscitation in severe sepsis. Brunkhorst FM, Engel C, Bloos F, Meier-Hellmann A. N Engl J Med. 2008;358(2):125.
12. Comparison of two fluid-management strategies in acute lung injury. National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome (ARDS) Clinical Trials Network, Wiedemann HP, Wheeler AP, N Engl J Med. 2006;354(24):2564).
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
Medications: Insulin, metformin, carvedilol, aspirin
Social: 20+ pack year history for tobacco, occasional alcohol and no illicit drugs
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.
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:
VBG: pH-7.29 pCO2-19.7
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
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
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.
- In altered mental status, especially in the elderly, really look at the SDS.
- If any salicylate level is detectable, consider chronic salicylate poisoning.
- Toxicity can look like just about anything, do not write it off too soon.
- Clinical picture really drives the necessity for dialysis.
- Intubate with extreme caution.
Additional information and resources:
American college of Medical Toxicology page for salicylism for more information.
UpToDate: Salicylate (aspirin) poisoning in adults.
Your local friendly Toxicologist