Intern Report 8.16

Case Discussion presented by Wissam Rhayem, MD

 

Chief Complaint:  “Chest Pain”

History of Present Illness:

This is a 26 y/o male prisoner presenting with a chief complaint of chest pain and palpitations.

The patient has a history of Wolff-Parkinson-White and poly-substance abuse. He states that he takes 20-40 mg of Xanax daily along with any Ativan, Klonopin, and Seroquel that he can obtain. The story is unclear, but the patient claims that he has been taking Xanax while in prison. The patient has been in prison for the last 9 days. He denies nausea, vomiting, headache, diarrhea, constipation, visual changes, fever, chills, or difficulty breathing.

Medications: Xanax 20-40 mg daily; Ativan; Klonopin; Seroquel; none are prescription

PMH: Wolff-Parkinson-White

Social History: + cannabis; + cigarettes; + alcohol weekly

 

Physical Exam:

VITALS: BP 127/80 HR 104 bpm T 36.1°C RR 16 bpm SpO2 98%

General: severe distress; agitated; not oriented

HEENT: pupils 3 mm; PERRL; EOMI; atraumatic

CV: regular rate and rhythm; no murmurs, rubs, or gallops

Pulmonary: breath sounds are clear bilaterally without rales, rhonchi or wheezing.

GI: soft, nontender, nondistended; no palpable masses

Musculoskeletal: no deformity; full ROM in all four extremities

Skin: no cyanosis; good perfusion in all four extremities; palpable pulses in all extremities

Neuro: not oriented; uncooperative; no focal deficits; normal deep tendon reflexes

Psych: uncooperative; agitated; labile mood; hostile; belligerent; pressured speech

Labs/Studies:

EKG: no delta wave; shortened PR interval; normal sinus rhythm

BMP: Na 139; K 4.0; Cl 104; CO2 30; BUN 11; Creatinine 0.99; Glucose 117

CBC: WBC 9.1; HgB 14.7; Hct 44.2; Plt 220

UDS: + BZDA; + cannabinoids

TROP: < 0.017 x 2

 

Medical Course:

While the patient is waiting for transfer to CDU,  his mental status begins to deteriorate. Now at 24 hours after initial presentation, he starts having visual hallucinations and becoming very agitated and delirious. He is demanding “footballs” and “candy bars.” The patient is screaming and is very verbally abusive. He is tugging violently at his restraints and is fighting to get out of bed. He does not respond to an initial 10 mg of IV Valium (diazepam). He is then given 10 mg, then 20 mg, then 40 mg, then 80 mg of IV Valium, each 5 minutes apart, until light sedation is achieved. At this point, he reports that his chest pain has resolved.

After about 90 minutes of sleep the patient sits straight up in bed, screaming for a urinal. The patient is now tachycardic and hypertensive. He is given a urinal and voids 900 mL of urine. Tachycardia and hypertension immediately resolve. He is noted to have tongue fasciculations and hand tremors at this time. He starts to become extremely agitated again and is given 20 mg, then 40 mg, then 80 mg, and then 160 mg of IV Valium each 5 minutes apart until he sleeps. A foley is placed to avoid further urinary retention.

Hospital pharmacy warns that they are running out of Valium. A propofol drip is then started. In the process of starting the drip, the patient becomes agitated again and requires 40 mg of IV Valium, followed by another 40 mg of IV Valium 5 minutes later. The drip is started at 20 mcg/kg/min. The patient is lightly sedated at this point, but continues trying to get out of bed. The drip is increased to 30 mcg/kg/min and the patient achieves light sleep. He is asleep soundly and snoring but responds to verbal stimuli. Saturations remain at 98% without supplementary oxygen. He is admitted to the MICU.

 

Questions:

1. Which of these is indicated in treatment of acute benzodiazepine overdose?

A. activated charcoal

B. gastric lavage

C. flumazenil

D. naloxone

E. supportive care

 

2. What are sequelae of benzodiazepine withdrawals?

A. agitation

B. seizures

C. hallucinations

D. nausea

E. all of the above

 

3. Which BZDA has a risk of propylene glycol poisoning when given IV for prolonged periods?

A. ativan/lorazepam

B. versed/midazolam

C. xanax/alprazolam

D. klonopin/clonazepam

E. onfi/clobazam

 

Bonus:

4. What is the approximate LD50 of Valium (diazepam)?

A. 1 mg/kg

B. 10 mg/kg

C. 100 mg/kg

D. 1000 mg/kg

E. unknown

 

Answers:

1. E

2. E

3. A

4. E

Discussion:

GOAL: The benzodiazepines are a class of medications that are critical to the armamentarium of emergency medicine physicians. In order to never harm a patient, it is important to touch up on some important facts and continue to think critically about the medication and the patient every single time one places an order for a benzodiazepine. Learning the short-term and long-term effects as well as the limitations of medications allows physicians to be more confident when using these medications.

1. Which of these is indicated in treatment of benzodiazepine overdose?

E. SUPPORTIVE CARE

We are taught in our didactic teachings and USMLE exams that Flumazenil is the antidote for benzodiazepine overdose. Yet, in the setting of the Emergency Department, there is relatively little utility to Flumazenil, for more than one reason. Primarily, Flumazenil has been known to lower seizure threshold in chronic Benzodiazepine users, and this is a risk that is just not worth taking when the patient rarely needs anything more than supportive care. Additionally, there is rarely a situation during which we can be fully confident that the patient we are treating has no other co-ingestions in addition to the benzodiazepines, and there are many documented cases in literature demonstrating seizures in patients with co-ingestions that receive Flumazenil.

There is no place for gastric lavage or activated charcoal in the treatment of benzodiazepine overdose. In fact, in treatment of benzodiazepine overdose without co-ingestion of another drug or alcohol, the patient is likely to benefit most from simple supportive therapy with IV fluids and airway protection. If the patient is not responding well, or requires a rapid return of mental status, such as in the case of accidental iatrogenic overdose, the patient may be treated with Flumazenil. Flumazenil may be given in boluses of 0.3 mg IV spaced at 5 minute intervals for a maximum of 3 mg/hr.

2. What are the sequelae of benzodiazepine withdrawals

E. ALL OF THE ABOVE

Benzodiazepines themselves work at the GABA receptors of cell membranes, allowing for an increase in opening frequency of the chloride ion channel, which hyper polarizes the cell, therefore causing an increased potentiation of the GABA neurotransmitter’s overall inhibitory properties. Therefore, sudden lack of the drug after prolonged use causes a hyperactive state so to speak. The patient may become incredibly agitated or aggressive, even psychotic. Patients can have hallucinations, seizures, insomnia, muscle spasms, and delirium.

3. Which BZDA has a risk of propylene glycol poisoning when given IV for prolonged periods?

A. ATIVAN/LORAZEPAM

Propylene glycol is used as a diluent in the formulation of IV preparations of both Ativan (lorazepam) and Valium (diazepam) to help dissolve the drug into the solution. The prolonged IV administration of either of these two drugs causes an increase in the concentrations of propylene glycol, which causes a constellation of symptoms of toxicity much like that of ethylene glycol. These begin with CNS depression, seizures, coma, and GI irritation. This can follow with tachypnea, pulmonary edema, tachycardia, hypertension, pneumonitis, or shock. Finally, the toxicity affects the kidneys, causing flank pain, hematuria, oliguria, or proteinuria. This can be fatal, and therefore avoiding the use of these two medications in prolonged IV administration is recommended.

4. What is the approximate LD50 of Valium (diazepam)?

E. UNKNOWN

It is true that this is truly unknown. Mice have an LD50 of ~700 mg/kg whereas rats have nearly ~1200 mg/kg. The important point is that Valium has an incredibly high therapeutic index of 1000:1, meaning the lethal dose is 1000 times higher than the effective dose. This is a comforting fact when administering such large doses as was given above. As patients are supportively monitored, there is often times recovery without permanent symptoms from acute intoxication. There are cases of acute ingestion of 2000 mg and 500 mg of diazepam with suicidal intent documented in case studies in 1978. The patients both fell into moderately deep comas but awoke with just supportive care and were discharged from the hospital within 48 hours of admission.

References:

Rapid Recovery From Massive Diazepam Overdose. David J. Greenblatt, MD; Elaine Woo, MD; Marcia Divoll Allen, RN; Paul J. Orsulak, PhD; Richard I. Shader, MD. JAMA. 1978;240(17):1872-1874.

Fatal seizures after flumazenil administration in a patient with mixed overdose. Haverkos, DiSalvo, Imhoff. Ann Pharmacother. 1994 Dec;28(12):1347-9.

Senior Report 8.15

Case Presentation by Brian Holowecky, MD

CHIEF COMPLAINT  “I have a sore throat and I cannot breathe”

HISTORY OF PRESENT ILLNESS
54-year-old female presents to the emergency department brought by ambulance for sore throat. She states she has had a sore throat since this morning and it has been getting progressively worse. Her throat feels like it is “closing up.” She called the ambulance because she was having increasing difficulty catching her breath. She feels a swelling in her throat which is causing her to be unable to drink or eat anything. She has a history of allergy to lisinopril. She has had angioedema reactions.  She admits to using crack cocaine last night out of a pipe in which she has done many times in the past. No fevers. No upper respiratory symptoms recently. No recent coryza symptoms. On further questioning she states that but used a larger amount of cocaine than usual last night.

REVIEW OF SYSTEMS:  Negative except as in HPI

PAST MEDICAL/SURGICAL HISTORY  History of angioedema, Hypertension, diabetes, asthma, bipolar disorder,
MEDICATIONS:  Albuterol, fluticasone, fluoxetine, clonidine, amlodipine, loratadine, omeprazole.
ALLERGIES:  Lisinopril, anaphylactic.
SOCIAL HISTORY:  Tobacco use, recent crack cocaine use yesterday by a pipe inhalation, heroin abuse. Recently attempted inpatient rehabilitation for drug abuse.

PHYSICAL EXAM
Vitals: BP 166/93 heart rate 58 respirations 16 temp 37.0 saturation 100% on room air.
General: Well nourished patient appearing mildly toxic in respiratory distress. She is hoarse. There is some questionable stridor.

HEENT:  Posterior pharynx is mildly erythematous initially. Mucuous membranes moist. No cobblestoning. Uvula is midline. Mallampati score is 2. Lips are not swollen. No periorbital edema.

Cardiovascular:  S1 S2. RRR. No murmurs. Peripheral pulses equal bilaterally.

Respiratory: Hoarse voice. Stridor. Increased work of breathing. Sitting forward in sniffing position. Breath sounds are equal. No wheeze or crackles. Tolerating secretions initially.

Gastrointestinal:  Soft, NT ND. No rebound, guarding, or rigidity.

MSK/Extremities:  No gross deformities. No joint swelling, erythema. No edema.

Skin:  Warm and dry. No rashes, bruises, or abrasions.

Neurologic:  Alert and Oriented. Follows commands. No facial asymmetry noted. Motor and sensation intact.

Medical Course:  
Initially concerned for anaphylactic reaction in this patient with a known history of anaphylaxis. She was appearing very anxious and beginning not to tolerate her secretions very well. There was slight drooling. I was concerned based on her deterioration for anaphylactic reaction. She began to get more hoarse of voice and to sit forward in the sniffing position. There was questionable stridor.

She received 0.1 mg of epinephrine IM, along with Zantac, 125 mg of Solu-Medrol, 50 mg of IV Benadryl. She did improve somewhat at that time.

The working diagnosis was possible anaphylactic reaction versus anxiety or panic attack. This is a patient with a known psychiatric disorder. She was placed on the cardiac monitors and continuous pulse ox. IV access was established. She began to tolerate her secretions better at that time. Her heart rate remained in the 50s to 60s. Saturation remained 100% on room air.

About 90 minutes into her ER visit, she appears to be worsening and begins tripoding, drooling more profoundly and acting considerably more anxious.  Shas never had any visible airway swelling.

A lateral neck xray is taken:

Questions:  

1) What is the most likely cause for her condition?
A) Anaphylactic reaction from unknown source
B) Thermal pharyngeal Injury
C)Neoplastic transformation of a previously benign lesion
D)That is a normal lateral neck xray. There is no abnormality.

2) What is the treatment for her condition?
A) Urgent intubation in a controlled environment
B) Admission an ICU for close airway monitoring
C) Steroids, antihistamines, and H2 blockers.
D) Antibiotics and ENT consult for drainage.

3) If you suspect anaphylaxis, what is the appropriate initial treatment?
A) 0.3 mg epi subQ, 50mg diphenhydramine, 150 mg ranitidine, steroid
B) 0.3 mg epi IM, 50mg diphenhydramine, 150 mg ranitidine, steroid
C) 0.1 mg epi sub Q, 50mg diphenhydramine, 150 mg ranitidine, steroid
D) 0.1 mg epi IM, 50mg diphenhydramine, 150 mg ranitidine, steroid

Bonus Question 1: Should an epipen be administed into the thigh of the person with the suspected anaphylactic reaction, or into the thumb of the person holding the autoinjector?
A) Thigh
B) Thumb

Bonus Question 2:  Do vaccines cause autism?
A) Yes
B) No

Answers:
1) B
2) A
3) B

Bonus Questions:
4) B
5)B

Discussion:
This patient ended up being found to have crack cocaine induced probable thermal epiglottitis.  It presented atypically, which is how epiglottitis tends to present in adults.  Epiglottitis is a rare finding in the post vaccination world.  Thermal injury is known to cause edema and epiglottitis.  Embers from a pipe or bong may be inhaled and cause thermal burns to epiglottis. In this case no thermal burn was visualized, but patient had clear epiglottitis presumably from cocaine. Imminent airway compromise is possible, if not suspected and treated appropriately.  Crack cocaine is known to cause “crack lung” but crack cocaine epiglottitis has only been reported once before in the early 1990s.

When suspicious for epiglottitis the appropriate course of action is to proceed with intubation with extreme caution.  Laryngeal and epiglottic spasm is very common.  Intubation in the OR with preparation for a surgical airway is desirable.  The diagnosis can be made with lateral neck xray as it was in this case, however another way is by direct visualization with fiberoptic ENT scoping.

Anaphylactic reaction was on the differential and the patient received treatment for anaphylactic reaction, albeit somewhat incorrectly.  Subcutaneous epinephrine has been shown to be less efficacious than intramuscular administration.  In cases of anaphylaxis, the subcutaneous vasculature is constricted and so dissemination of the epinephrine systemically is delayed as compared with intramuscular direct administration.  Remembering dosing and administration is critically important in timely management of anaphylaxis, and epiglottitis too.

Intern Report 8.14

Case Presented by Brett Sorge, MD

CHIEF COMPLAINT(S): Chest pain and SOB

HISTORY OF PRESENT ILLNESS:
This is a 67 yo male with HTN, hyperlipidemia and DM who presents with chest pain. His chest pain started this morning (14 hours ago) and is pressure-like and located around the center of his chest. The pain does not radiate, and has not gone away. He is having SOB as well, and feels like he has worse pain with deep breaths. He has had chills since this morning. He has had nausea and vomiting starting today as well. He has had four episodes of non-bloody vomiting total. He admits to a separate epigastric pain as well, that is worse with defecation. The pain does not radiate, and comes and goes. Previous to this morning, he had been tolerating diet with no N/V. He has had pale colored stool ever since a cholecystectomy 3 months ago and has noticed “Vernors”-colored urine. He denies skin changes, itching, or yellowing of his eyes. He denies recent travel, smoking, cough, diarrhea, bright red blood per vomit/rectum, history of cancer or blood clots.

REVIEW OF SYSTEMS:
CONSTITUTIONAL: No weight loss.
HEENT: No loss in vision, No runny nose.
SKIN: No rash
GASTROINTESTINAL: No black or bloody stools.
GENITOURINARY: No burning on urination.
NEUROLOGICAL: No syncope
MUSCULOSKELETAL: No loss of muscle function.
HEMATOLOGIC: No history of easy bruising.
LYMPHATICS: No history of splenectomy.
PSYCHIATRIC: No history of depression or anxiety.
ENDOCRINE: No polyuria or polydipsia.
ALLERGIES: No history of asthma.

PMD: Patient says he goes to an outside provider for his primary care

PAST MEDICAL HISTORY: Hyperlipidemia, hypertension, diabetes
SURGICAL HISTORY: Cholecystectomy 3 months ago, s/p laparotomy from GSW 30 yrs ago
MEDICATIONS: Patient does not know medications he takes – EMR- metoprolol 50 QD, amlodipine 5 mg QD, losartan 100 QD, atorvastatin 40 QHS, pioglitazone 45 QD
ALLERGIES: Lisinopril
SOCIAL HISTORY: Denies smoking cigarettes, drink alcohol, drug use
FAMILY HISTORY: No family history of early MIs

PHYSICAL EXAM: 
General: Laying in bed, appears uncomfortable.
Vitals: Blood pressure 215/94, pulse 90, respirations 16, temperature 38.1. Pulse oximetry 100% on room air
HEENT: Head exam was generally normal. No scleral icterus. Mucous membranes were moist.
Cardiovascular: Regular rate and rhythm, no murmurs rubs or gallops
Respiratory: Clear to auscultation bilaterally
Gastrointestinal: Tender to palpation of the epigastric area, soft, non-distended, + BS, multiple scars from previous surgeries
Musculoskeletal: Able to move all extremities
Neurologic: Neurologically, the patient was awake, alert, and oriented to person, place and time. There were no obvious focal neurologic abnormalities. No asterixis or tremor noted.

LABS:
BMP – 138/3.7/103/25/14/0.86/158 Ca – 9.6
LFT – ALT-724, AST-1637, Alk Phos – 379, t bili – 2.2, d bili – 1.4
Lipase – 63, Ammonia – 69, Lactic Acid – 2.6
CBC – 15.4/13.5/41.7/251
Coags – 23.1, 11.3, 1.06
Troponin – <0.017
EKG – normal
CXR – normal
US RUQ- dilated common bile duct without signs of stone, abscess, or an intra-hepatic process

 

QUESTIONS:

1. What is the most common symptom in ascending cholangitis?
A. Malaise
B. Jaundice
C. Fever
D. RUQ pain

2. What is the mortality without surgical decompression after 72 hours?
A. 30%
B. 60%
C. 85%
D. 100%

3. Of the answers provided, which antimicrobial therapy is best for empiric therapy for severe cholangitis?
A. azithromycin
B. ceftriaxone
C. ceftriaxone and metronidazole
D. vancomycin

Answers: 1. C, 2. D, 3. C

Discussion:
Many patient’s who present with ascending cholangitis present without classic signs and symptoms.  Classically, patients would present with RUQ pain, fever and jaundice. However, some recent studies have shown that these symptoms may only be present 15-20% of the time. The key symptom is fever, which is present in 90% of patient’s.  Factors that play a role in the pathogenesis of the disease involve an obstruction or an increase in luminal pressure that leads to a bacterial infection.  Risk factors include stones, recent cholecystectomy, ERCP, history of cholangitis, or HIV.  Bacteria are thought to invade the obstructed biliary tree in a retrograde fashion.  The most common bacteria involved are E coli, klebsiella, enterococcus, and bacteroides.  Work-up will show elevated WBC in 79% of patients, with LFT’s indicating cholestasis, with hyperbilirubinemia and an increased alkaline phosphatase level.  The most common sign on ultrasound will be a dilated common bile duct which is only present 64% of the time.  If there is a high clinical suspicion the patient can be taken for ERCP for both diagnosis and therapy.  Empiric anti-microbial therapy should be aimed at treating gram negative, gram positive and anaerobic bacteria. Drainage and decompression are required, with a mortality rate approaching 100% if this is delayed 72 hours.

Intern Report 8.13

Case Presentation by Lauren Kroll, MD

Chief complaint: “I can’t breathe.”

HISTORY OF PRESENT ILLNESS
This patient is a 49 year old female with a past medical history of alcohol abuse who presents to the Emergency Department as a medical code for difficulty in breathing. The patient states her difficulty in breathing started gradually last night, and that it is getting progressively worse. She has never experienced anything like this before. She denies fever, chills, cough, congestion, chest pain, and leg swelling. She does admit to some mild epigastric pain, which has been present for the past two days. The epigastric pain is accompanied by nausea and multiple episodes of non-bloody, non-bilious vomiting.

Past medical history: Hypothyroidism, seizure disorder, deep venous thrombosis (diagnosed in December 2014), alcoholism.
Past surgical history: None.
Medications: None (the patient does state she is supposed to be on both levothyroxine and coumadin).
Allergies: Dilantin, phenobarbital.
Social history: Significant for both tobacco and heavy alcohol abuse. No intravenous drug abuse.

PHYSICAL EXAM
Vitals: BP 119/84, HR 126, RR 38, T 35.4, SaO2 99% (room air)

General: Well developed African American female in respiratory distress.

HEENT: Normocephalic, atraumatic. No conjunctival pallor. No scleral icterus. Dry mucous membranes. No pharyngeal erythema. The patient’s breath has a fruity odor.

Cardiovascular: Tachycardic, regular rhythm. No murmurs. No jugular venous distention, no edema.

Respiratory: Tachypnic. Lungs clear to auscultation bilaterally, no wheezes or crackles. No accessory muscle use, no retractions.

Gastrointestinal: Abdomen soft, slightly tender to palpation in the epigastric area, and non-distended. No rebound tenderness, no guarding. Bowel sounds present.

Neurologic: Alert and oriented x 3. Strength equal in all four extremities.

Skin: Warm, dry.

DIAGNOSTIC STUDIES
EKG:

Laboratory studies:

Basic metabolic panel: Na 137, K 4, Cl 98, HCO3 5, BUN 13, Cr 1.06, glucose 122

Complete blood count: WBC 15.7, Hb 14.2, Hct 43.5, platelets 338

Coagulation studies: PT 10.9, PTT 29.2, INR 1.03

Arterial blood gas: pH 6.879, pCO2 22.1, pO2 95, HCO3 4

Beta-hydroxybutyrate 77.5 (normal 0.2 – 2.8)

Troponin <0.017

NT-PRO BNP 162

Liver function tests: amylase 97, lipase 888, total bilirubin 0.4, direct bilirubin 0.1, ALT 21, AST 68, alkaline phosphatase 98, albumin 2.9

EtOH 151

Urinalysis: 2+ ketones, 2+ protein, specific gravity 1.010, otherwise unremarkable

Chest x-ray:

Questions:
1. The patient’s acid base status is best described as which of the following?
A) anion gap metabolic acidosis (with complete respiratory compensation)
B) non-anion gap metabolic acidosis (with complete respiratory compensation)
C) anion gap metabolic acidosis (with incomplete respiratory compensation)
D) non-anion gap metabolic acidosis (with incomplete respiratory compensation)

2. Initial Emergency Department fluid management for this patient should include which of the following?
A) 5% dextrose in normal saline + insulin
B) 5% dextrose in normal saline + thiamine
C) 5% dextrose in water + thiamine
D) 5% dextrose in water + 3 amps of NaHCO3

3. As the patient is treated in the Emergency Department, which of the following would be expected with repeat blood draws and urinalysis?
A) beta-hydroxybutyrate will decrease; urine ketones will decrease
B) beta-hydroxybutyrate will decrease; urine ketones will remain unchanged
C) beta-hydroxybutyrate will increase then decrease; urine ketones will decrease
D) beta-hydroxybutyrate will decrease; urine ketones will increase then decrease

Answers & Discussion
1) C
2) B
3) D

1. The patient’s acid base status is best described as which of the following?
A) anion gap metabolic acidosis (with complete respiratory compensation)
B) non-anion gap metabolic acidosis (with complete respiratory compensation)
C) anion gap metabolic acidosis (with incomplete respiratory compensation)
D) non-anion gap metabolic acidosis (with incomplete respiratory compensation)

1) In interpreting this patient’s arterial blood gas, we first look at the pH. pH is 6.879; this is an acidosis.

2) Next, in order to determine whether this is a metabolic or a respiratory acidosis, we look at the pCO2. pCO2 is 22.1 (low); therefore, this is a metabolic acidosis.

3) Next, we calculate the patient’s anion gap (anion gap = Na – Cl – HCO3). Anion gap is 34 (high); therefore, this is an anion gap metabolic acidosis. Don’t forget, the patient’s expected anion gap can be determined by multiplying her albumin by three; given her albumin of 2.9, we would expect her anion gap to be approximately 8.7.

4) Next, we can use Winter’s formula (expected pCO2 = 1.5(HCO3) + 8 +/-2) to determine whether or not the patient’s respiratory status is completely compensating for her metabolic derangements. This patient’s expected pCO2 is 15.5, but her actual pCO2 is 22.1; therefore, her respiratory compensation is incomplete.

This patient’s diagnosis is alcoholic ketoacidosis (AKA). Like patients with diabetic ketoacidosis (DKA), those with AKA often also present with nausea and vomiting, which leads to a concomitant metabolic alkalosis. Therefore, it is important to remember that, while the patient’s primary acid base disturbance is an anion gap metabolic acidosis, it is possible for their serum pH to be acidemic, normal, or even alkalemic.

2. Initial Emergency Department fluid management for this patient should include which of the following?
A) 5% dextrose in normal saline + insulin
B) 5% dextrose in normal saline + thiamine
C) 5% dextrose in water + thiamine
D) 5% dextrose in water + 3 amps of NaHCO3

Again, this patient’s diagnosis is alcoholic ketoacidosis (AKA). AKA most commonly occurs in patients who chronically abuse alcohol and abruptly stop drinking; malnutrition and dehydration lead to ketone body formation. Initial Emergency Department management of AKA should include 5% dextrose in normal saline with thiamine added (to prevent Wernicke-Korsakoff Syndrome).

Insulin, although it is an important component of the Emergency Department management of diabetic ketoacidosis (DKA), is contraindicated in the treatment of AKA. Most patients with AKA do not demonstrate hyperglycemia (this patient’s glucose is 122). A bicarbonate drip can be considered in patients with pH < 7.1 (this patient’s pH is 6.879), but is not usually necessary and would not be the first step in managing this patient.

3. As the patient is treated in the Emergency Department, which of the following would be expected with repeat blood draws and urinalysis?
A) beta-hydroxybutyrate will decrease; urine ketones will decrease
B) beta-hydroxybutyrate will decrease; urine ketones will remain unchanged
C) beta-hydroxybutyrate will increase then decrease; urine ketones will decrease
D) beta-hydroxybutyrate will decrease; urine ketones will increase then decrease

In the body, beta-hydroxybutyrate is metabolized to acetoacetate and acetone. Urine dipsticks detect only acetoacetate (not beta-hydroxybutyrate). In alcoholic ketoacidosis (AKA), the initial ratio of beta-hydroxybutyrate to acetoacetate is high. However, as the patient receives treatment, beta-hydroxybutyrate will be metabolized and its serum concentration will decrease. Because beta-hydroxybutyrate is metabolized to acetoacetate and acetone, urine concentrations of acetoacetate (and, thereby, urine ketones) will transiently increase, then decrease.

Teaching Pearls

1. Suspect alcoholic ketoacidosis in a patient with a history of alcohol abuse who presents to the Emergency Department with an anion gap metabolic acidosis, ketonuria, elevated beta-hydroxybutyrate, and a normal blood glucose.

2. In addition to an anion gap metabolic acidosis (the primary acid base disturbance in alcoholic ketoacidosis), patients often also present with nausea and vomiting, which leads to a concomitant metabolic alkalosis.

3. Treatment of alcoholic ketoacidosis includes 5% dextrose in water, with thiamine added. A bicarbonate drip can be used in cases where the patient’s pH is less than 7.1.

 

References

Marx JA, Hockberger RS, Walls RM, et al. Rosen’s Emergency Medicine Concepts and Clinical Practice. 8th edition. 2014.

Rosh Review.

UpToDate. Fasting ketosis and alcoholic ketoacidosis. http://www.uptodate.com/contents/fasting-ketosis-and-alcoholic-ketoacidosis. Accessed January 2015.

Intern Report 8.12

Case Presentation by Jacob Jensen, MD

Chief complaint: nausea and vomiting

HPI: Patient is a 28 year old female with past medical history of developmental delay, schizophrenia, and hypothyroidism transferred to the ED from a skilled nursing facility for nausea and vomiting. Patient is not responding to questions, she is not accompanied by family or nursing home staff, and EMS is unable to supply further details. Per EMR review, patient is often transferred to this or other nearby hospitals with similar complaints (especially the day before holiday weekends).

ROS: Could not be obtained 2/2 patient’s underlying medical presentation.

PMH: Developmental delay, schizophrenia, hypothyroidism

PSH: There is a reference to an X-lap in the EMR but no explanation as to when or why it was performed.

SHx: Patient has resided in a skilled nursing facility for at least the last 10 years

All: NKDA

Meds: seroquel, trazadone, respiredone, cogentin, synthroid,

Physical exam:
Vitals: T 36.4 Oral, HR 137, BP 49/33, RR 22, SpO2 97% on room air
General: Alert but non-verbal
Eye: Extraocular movements are intact
HENT: Normocephalic, Atraumatic, Oral mucosa is dry
Respiratory: Respirations are non-labored
Cardiovascular: Normal S1, S2, no murmurs, rubs, or gallops
Gastrointestinal: Soft, mildly distended, no rebound or guarding
Musculoskeletal: No deformity
Integumentary: Cool, dry, intact

Course in the ED:
Patient was triaged to resuscitation bay due to hypotension with tachycardia. A 16 gauge IV was started and patient was given 2L normal saline. On repeat testing, patients HR had decreased to 118 and BP had increased to 92/70.

Patient had one witnessed episode of vomiting in the ED. The vomitus smelled feculent so an NGT was placed. 300mL of yellow-green gastric contents was returned.

Basic labs were as follows; Bedside Glucose unremarkable, Lactic Acid 9.7, BMP unremarkable, CBC remarkable for leukocytosis of 13.1 with absolute neutrophil count of 9.7, coags unremarkable, urinalysis unremarkable, and urine pregnancy negative.

Chest X-ray was unremarkable.

EKG was unremarkable.

Abdominal series was obtained and read as suggestive of high-grade distal small bowel obstruction.

 

The patient is transferred to the module and a surgery consult is placed. On reexamination, HR is 115, BP is 120/68. The patient is now nodding and shaking her head in response to questions. When asked if she has any pain, she indicates her abdomen. Her abdomen is still mildly distended and diffusely TTP without guarding or rebound.

Questions:
A) What is the most likely cause of lactic acidosis in this patient?

1. Increased pyruvate production
2. Reduced entry of pyruvate into mitochondria
3. Accumulation of NADH
4. Impaired gluconeogenesis
5. Metabolization of glucose by intestinal bacteria

B) What is the best fluid replacement option in this situation?

2. Crystalloid (Normal Saline or Lactated Ringer)
3. Buffer therapy (0.45% saline solution with 75mmol/L of sodium bicarbonate)
4. Blood products
5. Albumin
6. Hyperoncotic starch

C) What further diagnostic studies, if any, are called for?

3. No further studies are necessary
4. Check patient’s D Dimer
5. Check patient’s liver function; AST, ALT, Alk. phos.
6. Abdominal CT angiogram
7. Exploratory laparotomy

Answers & Discussion
1) 3
2) 2
3) 6

A) What is the most likely cause of lactic acidosis in this patient?

1. Increased pyruvate production
2. Reduced entry of pyruvate into mitochondria
3. Accumulation of NADH
4. Impaired gluconeogenesis
5. Metabolization of glucose by intestinal bacteria

B) What is the best fluid replacement option in this situation?

2. Crystalloid (Normal Saline or Lactated Ringer)
3. Buffer therapy (0.45% saline solution with 75mmol/L of sodium bicarbonate)
4. Blood products
5. Albumin
6. Hyperoncotic starch

C) What further diagnostic studies, if any, are called for?

3. No further studies are necessary
4. Check patient’s D Dimer
5. Check patient’s liver function; AST, ALT, Alk. phos.
6. Abdominal CT angiogram
7. Exploratory laparotomy

Discussion

1. First a quick recap of lactate production in human cells. In glycolysis, glucose is broken down into two pyruvate molecules. This pathway produces a total of 2 ATP, and also converts two molecules of NAD+ into two molecules of NADH. In aerobic environments, the two molecules of pyruvate can then be transported into the mitochondria to participate in the citric acid cycle producing more NADH. Finally, NADH is converted back to NAD+ in the electron transport chain of the mitochondrial matrix, creating a proton gradient that is used to produce more ATP. However, the electron transport chain can not operate in an oxygen poor environment. This means that without oxygen, the cell can not convert NADH back to NAD+. The solution to this problem is anaerobic glycolysis, during which pyruvate is converted into lactate, a process which regenerates NAD+.

 

 

 

 

Lactate, or lactic acid, can then be further oxidized into water and carbon dioxide or used by hepatocytes as the substrate for gluconeogenesis in the liver. Of note, human cells produce the L isomer of Lactic acid while bacteria can also produce the D-isomer which is not readily metabolized by human cells and can accumulate.

This patient presented in hypovolemic shock. It is not known how long she had been in this state, but it can be assumed that she has experienced some amount of end organ hypoperfusion. Insufficient oxygen delivery will result in the inability of mitochondria to maintain the activity of the electron transfer chain, resulting in a buildup of NADH. By Le Chatelier’s principle, an accumulation of NADH will drive the Pyruvate/lactate equilibrium toward the production of more lactate. This is what is causing our patient’s lactic acidosis.

Accumulation of NADH might also be secondary to increased metabolic demands such as during a grand mal seizure or intense exercise. However, this does not appear to be the case with this patient.

Increased pyruvate production (a) occurs in patients who have enzymatic defects affecting glycogenolysis or gluconeogenesis. This would most likely present in patients younger than 28 years old. Mitochondrial dysfunction (b) might also be secondary to genetic defects or it could be 2/2 drugs that cause mitochondrial damage. Examples of such drugs include Antiretrovirals and some antibiotics such as linezolid. There is no indication that this patient is taking any such medication.

Gluconeogenesis (d) mostly occurs in the liver. Patients with impaired liver function may have elevated lactic acid levels. Because this patient had an unremarkable coag profile, it is not likely that her liver is the source of her lactic acidosis.

D-Lactic acidosis (e) can be seen when intestinal bacteria are exposed to high levels of glucose. An example of this is patients with short gut syndrome. There is no indication that this patient would have increased levels of D-Lactic acid.

 

2. Crystalloids (a) are as effective as colloids at expanding plasma volume and saline has the advantage of being less expensive.

It has been thought that adding sodium bicarbonate to half normal saline (b) might help to buffer lactic acidosis while decreasing the chances of developing hyperchloremic acidosis, but this is controversial. At a minimum, patient’s serum pH and bicarbonate levels should be tested before beginning this therapy.

Blood replacement therapy (c) is indicated if patient is actively bleeding, or has a low hemoglobin and is symptomatic, none of which apply to this patient.

No advantage has been found for albumin (d) in hypovolemic resuscitation and hyperoncotic starch (e) is not advised over concern for kidney injury.

 

3. After resuscitation from hypovolemic shock, this patient was found to have elevated lactic acid, leukocytosis, and small bowel obstruction. She is non-verbal, but she does indicate that she is experiencing abdominal pain even though her abdomen is soft and there are no peritoneal signs. In this instance, the physician should have a low index of suspicion for mesenteric ischemia. The “gold standard” to evaluate for mesenteric ischemia is a mesenteric angiogram, however, recent studies have shown that CT angiogram has a sensitivity of 96% and a specificity of 94%.

 

Abdominal pain, lactic acidosis, and leukocytosis are all very non-specific. It may be very tempting to attribute these abnormalities to the small bowel obstruction and treat for constipation (a). However, mesenteric ischemia has not yet been ruled out.

D Dimer (b) is also a very non-specific test and would have little impact on the management of this patient.

This patient’s coag profile is within normal limits. She is not jaundiced, and there is nothing in her social history to suggest liver failure. Liver function test (c) would not influence the outcome of this case.

Exploratory laparotomy (e) is necessary if the patient has signs of intestinal infarction or perforation. As patient is hemodynamically stable and is not exhibiting peritoneal signs, Ct is more appropriate at this time.

 

 

References:

1. “Biphasic CT with Mesenteric CT Angiography in the Evaluation of Acute Mesenteric Ischemia: Initial Experience”, Radiology, October 2003. Kirkpatric et. al.
2. “Fluid resuscitation with colloid or crystalloid solutions in critically ill patients: a systematic review of randomised trials”, British Medical Journal, March 1998, Schierhout
3. Rosen’s Emergency Medicine, eighth edition, 2014, pages 1221-1224, Marx
4. Uptodate, Causes of Lactic Acidosis, 2014 Emmett,
5. Uptodate, Overview of Intestinal Ischemia in Adults, 2014 Grubiel and Lamont
6. Uptodate, Treatment of Severe Hypovolemia or Hypovolemic Shock in Adults, 2014, Mandel and Palevsky