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Altered Mental Status and Tachycardia
The Journal of Emergency Medicine, Vol. -, No. -, pp. 1–6, 2015 Copyright Ó 2015 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter
Case Presentations of the Harvard Emergency Medicine Residencies
ALTERED MENTAL STATUS AND TACHYCARDIA Jonathan E. Slutzman, MD,* David P. Curley, MD, PHD,† Wendy Macias-Konstantopoulos, MD,‡§ and David F. M. Brown, MD‡§ *Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, †Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, ‡Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, and §Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts Corresponding Address: David F. M. Brown, MD, Department of Emergency Medicine, Massachusetts General Hospital, Founders 110, 55 Fruit Street, Boston, MA 02114
pertension, depression, anxiety, chronic headaches, and a tubal ligation. A medication list, although unable to be confirmed with the patient, included citalopram, divalproex, mirtazapine, lisinopril, etanercept, oxycodone, pantoprazole, and vitamin B12. Dr. David Brown: With the limited information about this patient, what was your initial approach to forming a differential diagnosis and beginning the diagnostic evaluation and management? Dr. Slutzman: Anytime one has a potentially unstable patient, regardless of cause, it is important to go back to the basics of the ABCs (airway, breathing, and circulation). In this particular case, she was initially protecting her airway and adequately oxygenating and ventilating. Her circulatory status was more concerning. With a reported history of hypertension, the current blood pressure of 105/70 mm Hg may have represented relative hypotension when compared with her baseline state. Combined with a heart rate as high as 250 beats/min, this was quite concerning. For this reason, defibrillator pads were rapidly placed on the patient, an electrocardiogram (ECG) was obtained, and she was placed on continuous monitoring. Additional large-bore i.v. access was established. Dr. Eric Nadel: What did the ECG reveal? Dr. Slutzman: The initial ECG showed a narrow-complex regular tachycardia with a rate of 230
Dr. Jonathan Slutzman: Today’s case is that of a 34-year-old woman who was brought to the Emergency Department (ED) with agitation and confusion. Initial notification was via a radio call from Emergency Medical Services (EMS) reporting that the patient’s family had called 911. She was reported to be combative and unable to respond to questions. Prehospital vital signs were blood pressure of 105/60 mm Hg and heart rate of 230 beats/min. The patient had been given 2 mg of intravenous (i.v.) lorazepam. The estimated time to arrival was approximately 5 min. When the patient arrived, she was confused and writhing on the stretcher with her hands clutching her abdomen. EMS providers indicated that the patient seemed to have become more responsive to questioning after receiving the benzodiazepine. Although history was very limited, she was able to answer some simple yes or no questions. She denied chest pain as well as current alcohol or drug abuse. She endorsed abdominal pain and shortness of breath. Vital signs on arrival were temperature 36.6 C (97.8 F), heart rate 250 beats/min, blood pressure 105/70 mm Hg, respiratory rate 32 breaths/min, and oxygen saturation 99% on room air. Although a complete history was unavailable, a brief initial search of the electronic medical record revealed a history of gastric bypass 4 years prior, Hashimoto’s thyroiditis, non-insulin-dependent diabetes, hy-
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beats/min (Figure 1). Electrical alternans was a prominent feature. Perhaps the most concerning cause of electrical alternans is cardiac tamponade. However, this diagnosis was rapidly eliminated from the differential with point-of-care cardiac ultrasound that was negative for pericardial effusion. Electrical alternans may also be seen with an atrioventricular accessory pathway. In fact, it has been reported that the finding of electrical alternans in sustained narrow complex tachycardia is near diagnostic of orthodromic atrioventricular reciprocating tachycardia (1). Sinus tachycardia was considered, but believed to be less likely due to the extreme rate. We also reviewed the ECG for evidence of drug toxicity but found a normal narrow QRS complex and short QTc duration. There was no prominent R wave in lead aVR to suggest significant sodium channel blockade, as would be expected in tricyclic antidepressant or diphenhydramine overdose. Dr. Brown: Can you describe the physical examination? Was there any other source of history? Dr. Slutzman: The patient was tearful, anxious, and clenching her teeth. Her pupils were 6 mm and symmetrically reactive bilaterally. The lungs had diffuse rhonchi bilaterally. There was tachypnea but no other signs of respiratory distress. Heart sounds were tachycardic but regular with no audible murmurs. The abdomen was soft and nondistended, without focal tenderness, although the patient was holding her hands against her lower abdomen. The extremities were without focal tenderness or deformity. On neurological examination, she was tremulous
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and writhing, with near continuous movement of all extremities. She responded inconsistently to some simple yes-or-no questions. Motor and sensory functions were grossly intact and gait was not assessed. Toward the end of the initial evaluation, the patient’s mother arrived. She described finding her daughter on the morning of presentation clenching her teeth and shaking. The patient’s mother reported that she does not drink alcohol in excess. However, under another medical record number, it appeared as though the patient may have had a prior visit for alcohol withdrawal. Dr. Nadel: Given that you had a patient you believed to be unstable, how did you proceed? Dr. Slutzman: We proceeded down diagnostic and therapeutic pathways rapidly and simultaneously. Our initial efforts were focused on restoring hemodynamic stability. Two liters of i.v. normal saline were infused. During the initial evaluation, a focused cardiopulmonary ultrasound showed grossly normal systolic function without pericardial effusion, right-sided heart strain, or pulmonary edema. There was no free fluid on focused abdominal ultrasound. The patient received additional doses of i.v. lorazepam to treat her psychomotor agitation and the possibility of alcohol withdrawal. A trial of 6 mg, then 12 mg of adenosine rapid i.v. push had no effect on the patient’s tachycardia. With a stable blood pressure and electrical alternans on ECG suggestive of a re-entrant tachycardia with a possible atrioventricular accessory pathway, the patient was treated with procainamide, but this also had no effect on her rate. She
Figure 1. Initial electrocardiogram shows narrow complex regular tachycardia at 230 beats/min with electrical alternans.
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Figure 2. Electrocardiogram immediately after direct-current cardioversion interpreted as sinus tachycardia at 182 beats/min.
received additional lorazepam and was premedicated for direct-current cardioversion with fentanyl. Two attempts at cardioversion were performed, with a decrease in heart rate to the 190s. The subsequent ECG rhythm (Figure 2) was also difficult to interpret, but appeared to be different from the initial presenting rhythm. This
new rhythm was interpreted as sinus tachycardia. In retrospect, this assessment was likely correct as the morphologies matched her ECG on admission to the intensive care unit (ICU) (Figure 3). Systolic blood pressure increased to 120 mm Hg. Given the patient’s clinical status, the decision was made to endotracheally
Figure 3. Electrocardiogram upon admission to the intensive care unit showing sinus tachycardia at 124 beats/min.
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intubate to facilitate safe further evaluation and management. Dr. David Peak: How did you develop your differential diagnosis? Dr. Slutzman: In a patient with altered mental status and hemodynamic instability, one must keep a broad differential diagnosis. Common potential causes include infection, intracranial hemorrhage, toxidromes, endocrinopathies, withdrawal syndromes, metabolic derangement, and seizure. There were no external signs of trauma on examination to suggest clinically significant injuries. Pulmonary, respiratory, abdominal, and central nervous system (CNS) sources of infection were discussed. The patient did seem to be localizing some symptoms to the lower abdomen. Taken in combination with the history of gastric bypass, this was felt to be the most likely source of infection, if one were present. Additional abdominal catastrophes were considered, including gastric remnant distension leading to anastomotic leak, perforation, or internal hernia. We also considered toxic and metabolic causes. She did not seem to be intoxicated by alcohol, but withdrawal was a significant possibility and fit with the apparent hypersympathetic state in which she presented. Similarly along the lines of hyperadrenergia would be acute thyrotoxicosis, although she was not hyperthermic. Toxic levels of sympathomimetics, including cocaine, and anticholinergics, including diphenhydramine, would also give a similar presentation. Seizures must also be considered in a patient with acute altered mental status as well as hyperadrenergia, especially with a history of reported shaking at home. To synthesize our differential, we felt the most likely causes of this patient’s clinical presentation, in order of decreasing likelihood, were substance use, withdrawal syndrome, sepsis, abdominal catastrophe, or a primary cardiac disorder. Dr. Brown: Can you describe the initial diagnostic evaluation? Dr. Slutzman: In addition to obtaining an ECG and continuous monitoring, labs including a blood gas, finger stick glucose, compete blood count (CBC), chemistry, lactate, thyroid function tests, cardiac biomarkers, blood and urine toxicology, urinalysis, blood cultures, and serum osmolarity were obtained. Additionally, a portable chest radiograph was ordered to assess for obvious thoracic pathology as well as possible subdiaphragmatic free air as a marker for viscous perforation. Focused bedside point-of-care cardiac and abdominal ultrasounds were performed, as already mentioned. Computed tomography (CT) scans of the head and abdomen were ordered. Dr. Nadel: This seems like a comprehensive evaluation. Can you take us through the patient’s initial lab results? Dr. Slutzman: Immediately after intubation, the initial lab results became available. CBC was remarkable for a
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white blood cell count of 15,900 per mm3. Chemistries revealed serum sodium 129 mmol/L, potassium 3.4 mmol/L, chloride 83 mmol/L, bicarbonate 14 mmol/L, blood urea nitrogen 6 mg/dL, creatinine 1.4 mg/dL, and glucose 181 mg/dL. The anion gap was 32, serum osmolarity 288, and osmolar gap 18. Lactate was 14.6 mmol/L. The patient had a normal bilirubin and mildly elevated transaminases, with aspartate transaminase 59 U/L and alanine transaminase 26 U/L. The lipase was 901 U/L. Thyroid-stimulating hormone was 1.54 mU/mL. Serum human chorionic gonadotropin was negative. Cardiac myocyte troponin-T was less than assay. A venous blood gas showed a pH of 7.51, CO2 of 24 mm Hg, and base deficit of 2.8. Urinalysis did not show evidence of an infection. A short time later, the toxicology results returned with an acetone level > 300 mg/L, diphenhydramine 179 mg/L (toxic > 200 mg/ L), and valproic acid < 3 mg/mL. An alcohol level was less than assay. Urine toxicology was negative for opiates, benzodiazepines, cocaine, amphetamines, barbiturates, phencyclidine, and tetrahydrocannabinol. In summary, our patient showed evidence of a mixed picture acid– base abnormality, with a primary respiratory alkalosis and metabolic acidosis. The laboratory data were helpful to exclude a number of diagnoses while leaving others to be further investigated. The high lactate value was suspicious for seizure, infection, intraabdominal catastrophe, and toxic ingestion. Most significant was the markedly elevated acetone level. Acetone can be elevated in diabetic ketoacidosis, although the patient’s serum glucose was not markedly elevated, urine analysis was negative for glucose, and pH did not indicate primary acidosis; in addition, she was not taking insulin, suggesting her diabetes was Type 2. Acetone is also a breakdown product of alcohol metabolism, specifically isopropyl alcohol (2propanol), which, coupled with elevated osmolal gap, is suggestive of a toxic alcohol ingestion. However, isopropyl alcohol metabolism would not be expected to generate an anion gap on its own. Of note, the patient’s toxicology studies did not find ethanol, methanol, or 2-propanol in her serum. It is also possible that the patient ingested acetone directly, although this is less common. The finding of diphenhydramine was considered less significant, as its concentration was below the typical toxic threshold to cause symptoms and the patient’s ECG did not appear to have typical stigmata of sodium channel blockade. Dr. John T. Nagurney: How did you explain this patient’s acid–base picture? Dr. Slutzman: This patient had a mixed acid–base abnormality. The patient was alkalemic, with a pH of 7.51 and pCO2 of 24 on blood gas. The primary problem was a respiratory alkalosis, as evidenced by the high pH and low pCO2, and was consistent with the patient’s tachypnea. In an acute respiratory alkalosis, the kidneys do not typically have enough time to compensate by
Altered Mental Status and Tachycardia
excreting bicarbonate buffer. Usually, in an acute setting, bicarbonate will decrease by 2–2.5 mmol/L for each drop of 10 mm Hg of pCO2 from a baseline of 40 mm Hg. (This is half the expected decrease in bicarbonate as would be seen in a chronic respiratory alkalosis.) This apparent overcompensation of bicarbonate for the respiratory alkalosis (14 mmol/L here vs. the expected minimum of 20 mmol/L) suggests a concurrent metabolic acidosis, which is also supported by the mild base deficit of 2.8, in this case likely due to lactic acid and acetone. Those looking for an alternative perspective on the acid–base picture can use physical chemistry principles. The strong ion difference (difference between serum sodium and chloride) was 46, which would ordinarily indicate a metabolic alkalosis. In this case, we suspect that it was counteracting the lactic acidosis. A high strong ion difference can also be suggestive of volume depletion or diuretic use. The strong ion gap was minimally negative, suggesting that there were no outstanding factors contributing to the patient’s acid–base status beyond sodium, chloride, lactate, and bicarbonate. Regarding the question of why the patient had a primary respiratory alkalosis, she was not hypoxemic to suggest a primary pulmonary cause, and she did not have evidence of salicylate toxicity. In this case, the respiratory alkalosis was likely due to hyperventilation, perhaps related to an increased drive to excrete acetone. Dr. Nadel: You had mentioned obtaining imaging studies. What were those results? Dr. David Curley: By the time imaging results were available, I had assumed care of the patient from my colleague. A portable chest X-ray study showed proper positioning of the endotracheal tube as well as a left lung base opacity consistent with atelectasis or aspiration. CT of the abdomen was unremarkable and a CT scan of the head showed no acute abnormalities. None of these findings were thought to explain the patient’s symptoms. The patient was admitted to the ICU. Dr. James K. Takayesu: This patient seems to have had a toxic ingestion. Can you describe how you thought about this? Dr. Curley: This patient had an anion gap of 32 and a lactate of 14.6 mmol/L. She was hyperadrenergic. We recognized that, in addition to the prominent respiratory alkalosis, she also had a metabolic acidosis and so we considered the various causes of this. A frequently taught mnemonic is MUDPILES. We quickly discounted uremia due to a normal blood urea nitrogen level, diabetic ketoacidosis with an unimpressively elevated serum glucose, isoniazid as it was not a medication to which she was thought to have access, and salicylate with a negative test. In particular, with a presumed toxic ingestion, one must consider the toxic alcohols: methanol, ethylene glycol, and propylene gly-
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col. Methanol is metabolized to formaldehyde and formic acid, mainly in the liver. Ethylene glycol is metabolized to glycolic acid and oxalic acid, which may cause CNS depression and seizures. Longer-term toxic effects of these metabolites include calcium oxalate crystal formation in the kidney and resulting acute kidney injury. Propylene glycol is a food and drug additive and less available to the general public. However, it is metabolized into pyruvic acid, acetic acid, lactic acid, and propionaldehyde. The initial effects of propylene glycol overdose are also CNS depression. Additionally, this patient had an elevated osmolar gap. Taken together, the patient was empirically treated with fomepizole, an alcohol dehydrogenase inhibitor. It is important to treat early with fomepizole, as it prevents the formation of toxic metabolites. Once the metabolism has already occurred, there is no benefit to this antidote. Cyanide must always be considered in the setting of a very elevated lactate. However, this patient’s clinical picture was not one of cyanide poisoning. Finally, it is extremely important to consider toxic co-ingestions such as acetaminophen whenever ingestion is suspected. The consequences of missing and not treating such a coingestion could be severe, even if you are able to steward the patient through their initial insult. Dr. Wendy Macias-Konstantopoulos: This patient seems to have been quite agitated. Did she fit into a toxidrome that helped aid in the diagnosis? Dr. Curley: Perhaps one of the most common toxidromes we see in the ED is that of sympathomimetics. Classic features include anxiety, diaphoresis, hyperreflexia, mydriasis, piloerection, hypertension, tachycardia, and seizures. Common causes are agents such as amphetamines, cocaine, and pseudoephedrine. Although this patient did not fit into any easily identifiable toxidrome, this was probably the closest to her presentation. Other common toxidromes to consider when a patient arrives include anticholinergic (delirium, anhydrosis, mydriasis, flushing, hyperthermia, seizures, and dysrhythmias), cholinergic (diaphoresis, urination, miosis, bradycardia, bronchorrhea, emesis, lacrimation, and salivation), opioid (respiratory depression, hypotension, miosis, bradycardia, seizure, and coma), and salicylism (tinnitus, hyperpnea, depressed mental status, and delirium). For various reasons mentioned above, our patient did not fit any of these additional syndromes. Dr. Brown: Can you tell us about the remainder of this patient’s course? Dr. Curley: Shortly after admission to the medical ICU, the patient’s husband came to the hospital and was able to provide additional history. The patient had reportedly been consuming up to a liter of vodka daily. However, she had run out of liquor approximately 3 days prior to this hospital admission and had begun
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drinking other household items such as NyQuil and Listerine. The family found an empty bottle of nail polish remover (which contains acetone) in her bed on the day of this presentation. Given this additional history, fomepizole was discontinued in the ICU. She was started on phenobarbital for alcohol withdrawal and subsequently extubated. The initial heart rhythm was considered most likely to be a supraventricular re-entrant tachycardia, likely in response to physiologic stress, adrenergic tone, toxic ingestion, and alcohol withdrawal. She had a transthoracic echocardiogram that revealed a structurally normal heart. She was treated with beta-blockade for persistent sinus tachycardia. The patient was seen by Psychiatry, who believed her presentation was most likely the result of alcohol dependence rather than an intent to self harm. Phenobarbital was tapered and the patient was discharged on hospital day 5. She has since followed up in clinic and is doing well. Dr. Peak: Is there anything we should know in particular about the potential effects and needed treatment of acute acetone ingestion? Dr. Curley: Strong medical literature data on human acetone toxicity are lacking, although case reports shed some light on typical presentations. A report in 1988 of a pediatric ingestion of acetone described respiratory depression, CNS depression, hyperglycemia, acidosis, and hypotension (2). These symptoms all resolved with supportive care. In its toxicologic profile of acetone, the Agency for Toxic Substances and Disease Registry (ATSDR) reported an oral LD50 of approximately 1.7–9.9 g/kg in rat studies (3). The no-observedadverse-effects level was reported as 0.8–12 mg/kg. Metabolically, acetone is either excreted unchanged via the kidneys or lungs or it is metabolized through multiple
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pathways to end products including glucose, D-lactate, L-lactate, acetate, and formate. Dr. Nagurney: Because this patient presented with agitation rather than CNS depression, and tachypnea rather than respiratory depression, do you think the acetone ingestion was complicated by another factor? Dr. Curley: Yes, we do. It is likely that this patient was suffering from acute alcohol withdrawal symptoms, perhaps inducing her to drink products that were on hand. Alcohol withdrawal syndrome is a hyperadrenergic state, which contributed to this patient’s tachydysrhythmia, mydriasis, and likely seizure at home (4). In fact, her lab values can be explained by these two opposing toxicologic effects affecting her simultaneously. Dr. Nadel: What are your take-home points from this case? Dr. Curley: Focusing on initial resuscitative measures to support a patient is key, to be followed by careful interpretation of lab and imaging findings to exclude or include parts of your differential diagnosis. Ultimately, though, it was the history provided by the patient’s husband that made the final diagnosis. REFERENCES 1. Green M, Heddle B, Dassen W, et al. Value of QRS alteration in determining the site of origin of narrow QRS supraventricular tachycardia. Circulation 1983;68:368–73. 2. Gamis A, Wasserman G. Acute acetone intoxication in a pediatric patient. Pediatr Emerg Care 1988;4:24–6. 3. Agency for Toxic Substances and Disease Registry, Public Health Service. Toxicological profile for acetone. Atlanta, GA: U.S. Department of Health and Human Services; 1994. 4. Awissi D, Lebrun G, Coursin D, Riker R, Skrobik Y. Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. Intensive Care Med 2013;39:16–30.
Case Presentations of the Harvard Emergency Medicine Residencies
ALTERED MENTAL STATUS AND TACHYCARDIA Jonathan E. Slutzman, MD,* David P. Curley, MD, PHD,† Wendy Macias-Konstantopoulos, MD,‡§ and David F. M. Brown, MD‡§ *Department of Emergency Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, †Department of Emergency Medicine, Alpert Medical School of Brown University, Providence, Rhode Island, ‡Department of Emergency Medicine, Harvard Medical School, Boston, Massachusetts, and §Department of Emergency Medicine, Massachusetts General Hospital, Boston, Massachusetts Corresponding Address: David F. M. Brown, MD, Department of Emergency Medicine, Massachusetts General Hospital, Founders 110, 55 Fruit Street, Boston, MA 02114
pertension, depression, anxiety, chronic headaches, and a tubal ligation. A medication list, although unable to be confirmed with the patient, included citalopram, divalproex, mirtazapine, lisinopril, etanercept, oxycodone, pantoprazole, and vitamin B12. Dr. David Brown: With the limited information about this patient, what was your initial approach to forming a differential diagnosis and beginning the diagnostic evaluation and management? Dr. Slutzman: Anytime one has a potentially unstable patient, regardless of cause, it is important to go back to the basics of the ABCs (airway, breathing, and circulation). In this particular case, she was initially protecting her airway and adequately oxygenating and ventilating. Her circulatory status was more concerning. With a reported history of hypertension, the current blood pressure of 105/70 mm Hg may have represented relative hypotension when compared with her baseline state. Combined with a heart rate as high as 250 beats/min, this was quite concerning. For this reason, defibrillator pads were rapidly placed on the patient, an electrocardiogram (ECG) was obtained, and she was placed on continuous monitoring. Additional large-bore i.v. access was established. Dr. Eric Nadel: What did the ECG reveal? Dr. Slutzman: The initial ECG showed a narrow-complex regular tachycardia with a rate of 230
Dr. Jonathan Slutzman: Today’s case is that of a 34-year-old woman who was brought to the Emergency Department (ED) with agitation and confusion. Initial notification was via a radio call from Emergency Medical Services (EMS) reporting that the patient’s family had called 911. She was reported to be combative and unable to respond to questions. Prehospital vital signs were blood pressure of 105/60 mm Hg and heart rate of 230 beats/min. The patient had been given 2 mg of intravenous (i.v.) lorazepam. The estimated time to arrival was approximately 5 min. When the patient arrived, she was confused and writhing on the stretcher with her hands clutching her abdomen. EMS providers indicated that the patient seemed to have become more responsive to questioning after receiving the benzodiazepine. Although history was very limited, she was able to answer some simple yes or no questions. She denied chest pain as well as current alcohol or drug abuse. She endorsed abdominal pain and shortness of breath. Vital signs on arrival were temperature 36.6 C (97.8 F), heart rate 250 beats/min, blood pressure 105/70 mm Hg, respiratory rate 32 breaths/min, and oxygen saturation 99% on room air. Although a complete history was unavailable, a brief initial search of the electronic medical record revealed a history of gastric bypass 4 years prior, Hashimoto’s thyroiditis, non-insulin-dependent diabetes, hy-
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beats/min (Figure 1). Electrical alternans was a prominent feature. Perhaps the most concerning cause of electrical alternans is cardiac tamponade. However, this diagnosis was rapidly eliminated from the differential with point-of-care cardiac ultrasound that was negative for pericardial effusion. Electrical alternans may also be seen with an atrioventricular accessory pathway. In fact, it has been reported that the finding of electrical alternans in sustained narrow complex tachycardia is near diagnostic of orthodromic atrioventricular reciprocating tachycardia (1). Sinus tachycardia was considered, but believed to be less likely due to the extreme rate. We also reviewed the ECG for evidence of drug toxicity but found a normal narrow QRS complex and short QTc duration. There was no prominent R wave in lead aVR to suggest significant sodium channel blockade, as would be expected in tricyclic antidepressant or diphenhydramine overdose. Dr. Brown: Can you describe the physical examination? Was there any other source of history? Dr. Slutzman: The patient was tearful, anxious, and clenching her teeth. Her pupils were 6 mm and symmetrically reactive bilaterally. The lungs had diffuse rhonchi bilaterally. There was tachypnea but no other signs of respiratory distress. Heart sounds were tachycardic but regular with no audible murmurs. The abdomen was soft and nondistended, without focal tenderness, although the patient was holding her hands against her lower abdomen. The extremities were without focal tenderness or deformity. On neurological examination, she was tremulous
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and writhing, with near continuous movement of all extremities. She responded inconsistently to some simple yes-or-no questions. Motor and sensory functions were grossly intact and gait was not assessed. Toward the end of the initial evaluation, the patient’s mother arrived. She described finding her daughter on the morning of presentation clenching her teeth and shaking. The patient’s mother reported that she does not drink alcohol in excess. However, under another medical record number, it appeared as though the patient may have had a prior visit for alcohol withdrawal. Dr. Nadel: Given that you had a patient you believed to be unstable, how did you proceed? Dr. Slutzman: We proceeded down diagnostic and therapeutic pathways rapidly and simultaneously. Our initial efforts were focused on restoring hemodynamic stability. Two liters of i.v. normal saline were infused. During the initial evaluation, a focused cardiopulmonary ultrasound showed grossly normal systolic function without pericardial effusion, right-sided heart strain, or pulmonary edema. There was no free fluid on focused abdominal ultrasound. The patient received additional doses of i.v. lorazepam to treat her psychomotor agitation and the possibility of alcohol withdrawal. A trial of 6 mg, then 12 mg of adenosine rapid i.v. push had no effect on the patient’s tachycardia. With a stable blood pressure and electrical alternans on ECG suggestive of a re-entrant tachycardia with a possible atrioventricular accessory pathway, the patient was treated with procainamide, but this also had no effect on her rate. She
Figure 1. Initial electrocardiogram shows narrow complex regular tachycardia at 230 beats/min with electrical alternans.
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Figure 2. Electrocardiogram immediately after direct-current cardioversion interpreted as sinus tachycardia at 182 beats/min.
received additional lorazepam and was premedicated for direct-current cardioversion with fentanyl. Two attempts at cardioversion were performed, with a decrease in heart rate to the 190s. The subsequent ECG rhythm (Figure 2) was also difficult to interpret, but appeared to be different from the initial presenting rhythm. This
new rhythm was interpreted as sinus tachycardia. In retrospect, this assessment was likely correct as the morphologies matched her ECG on admission to the intensive care unit (ICU) (Figure 3). Systolic blood pressure increased to 120 mm Hg. Given the patient’s clinical status, the decision was made to endotracheally
Figure 3. Electrocardiogram upon admission to the intensive care unit showing sinus tachycardia at 124 beats/min.
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intubate to facilitate safe further evaluation and management. Dr. David Peak: How did you develop your differential diagnosis? Dr. Slutzman: In a patient with altered mental status and hemodynamic instability, one must keep a broad differential diagnosis. Common potential causes include infection, intracranial hemorrhage, toxidromes, endocrinopathies, withdrawal syndromes, metabolic derangement, and seizure. There were no external signs of trauma on examination to suggest clinically significant injuries. Pulmonary, respiratory, abdominal, and central nervous system (CNS) sources of infection were discussed. The patient did seem to be localizing some symptoms to the lower abdomen. Taken in combination with the history of gastric bypass, this was felt to be the most likely source of infection, if one were present. Additional abdominal catastrophes were considered, including gastric remnant distension leading to anastomotic leak, perforation, or internal hernia. We also considered toxic and metabolic causes. She did not seem to be intoxicated by alcohol, but withdrawal was a significant possibility and fit with the apparent hypersympathetic state in which she presented. Similarly along the lines of hyperadrenergia would be acute thyrotoxicosis, although she was not hyperthermic. Toxic levels of sympathomimetics, including cocaine, and anticholinergics, including diphenhydramine, would also give a similar presentation. Seizures must also be considered in a patient with acute altered mental status as well as hyperadrenergia, especially with a history of reported shaking at home. To synthesize our differential, we felt the most likely causes of this patient’s clinical presentation, in order of decreasing likelihood, were substance use, withdrawal syndrome, sepsis, abdominal catastrophe, or a primary cardiac disorder. Dr. Brown: Can you describe the initial diagnostic evaluation? Dr. Slutzman: In addition to obtaining an ECG and continuous monitoring, labs including a blood gas, finger stick glucose, compete blood count (CBC), chemistry, lactate, thyroid function tests, cardiac biomarkers, blood and urine toxicology, urinalysis, blood cultures, and serum osmolarity were obtained. Additionally, a portable chest radiograph was ordered to assess for obvious thoracic pathology as well as possible subdiaphragmatic free air as a marker for viscous perforation. Focused bedside point-of-care cardiac and abdominal ultrasounds were performed, as already mentioned. Computed tomography (CT) scans of the head and abdomen were ordered. Dr. Nadel: This seems like a comprehensive evaluation. Can you take us through the patient’s initial lab results? Dr. Slutzman: Immediately after intubation, the initial lab results became available. CBC was remarkable for a
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white blood cell count of 15,900 per mm3. Chemistries revealed serum sodium 129 mmol/L, potassium 3.4 mmol/L, chloride 83 mmol/L, bicarbonate 14 mmol/L, blood urea nitrogen 6 mg/dL, creatinine 1.4 mg/dL, and glucose 181 mg/dL. The anion gap was 32, serum osmolarity 288, and osmolar gap 18. Lactate was 14.6 mmol/L. The patient had a normal bilirubin and mildly elevated transaminases, with aspartate transaminase 59 U/L and alanine transaminase 26 U/L. The lipase was 901 U/L. Thyroid-stimulating hormone was 1.54 mU/mL. Serum human chorionic gonadotropin was negative. Cardiac myocyte troponin-T was less than assay. A venous blood gas showed a pH of 7.51, CO2 of 24 mm Hg, and base deficit of 2.8. Urinalysis did not show evidence of an infection. A short time later, the toxicology results returned with an acetone level > 300 mg/L, diphenhydramine 179 mg/L (toxic > 200 mg/ L), and valproic acid < 3 mg/mL. An alcohol level was less than assay. Urine toxicology was negative for opiates, benzodiazepines, cocaine, amphetamines, barbiturates, phencyclidine, and tetrahydrocannabinol. In summary, our patient showed evidence of a mixed picture acid– base abnormality, with a primary respiratory alkalosis and metabolic acidosis. The laboratory data were helpful to exclude a number of diagnoses while leaving others to be further investigated. The high lactate value was suspicious for seizure, infection, intraabdominal catastrophe, and toxic ingestion. Most significant was the markedly elevated acetone level. Acetone can be elevated in diabetic ketoacidosis, although the patient’s serum glucose was not markedly elevated, urine analysis was negative for glucose, and pH did not indicate primary acidosis; in addition, she was not taking insulin, suggesting her diabetes was Type 2. Acetone is also a breakdown product of alcohol metabolism, specifically isopropyl alcohol (2propanol), which, coupled with elevated osmolal gap, is suggestive of a toxic alcohol ingestion. However, isopropyl alcohol metabolism would not be expected to generate an anion gap on its own. Of note, the patient’s toxicology studies did not find ethanol, methanol, or 2-propanol in her serum. It is also possible that the patient ingested acetone directly, although this is less common. The finding of diphenhydramine was considered less significant, as its concentration was below the typical toxic threshold to cause symptoms and the patient’s ECG did not appear to have typical stigmata of sodium channel blockade. Dr. John T. Nagurney: How did you explain this patient’s acid–base picture? Dr. Slutzman: This patient had a mixed acid–base abnormality. The patient was alkalemic, with a pH of 7.51 and pCO2 of 24 on blood gas. The primary problem was a respiratory alkalosis, as evidenced by the high pH and low pCO2, and was consistent with the patient’s tachypnea. In an acute respiratory alkalosis, the kidneys do not typically have enough time to compensate by
Altered Mental Status and Tachycardia
excreting bicarbonate buffer. Usually, in an acute setting, bicarbonate will decrease by 2–2.5 mmol/L for each drop of 10 mm Hg of pCO2 from a baseline of 40 mm Hg. (This is half the expected decrease in bicarbonate as would be seen in a chronic respiratory alkalosis.) This apparent overcompensation of bicarbonate for the respiratory alkalosis (14 mmol/L here vs. the expected minimum of 20 mmol/L) suggests a concurrent metabolic acidosis, which is also supported by the mild base deficit of 2.8, in this case likely due to lactic acid and acetone. Those looking for an alternative perspective on the acid–base picture can use physical chemistry principles. The strong ion difference (difference between serum sodium and chloride) was 46, which would ordinarily indicate a metabolic alkalosis. In this case, we suspect that it was counteracting the lactic acidosis. A high strong ion difference can also be suggestive of volume depletion or diuretic use. The strong ion gap was minimally negative, suggesting that there were no outstanding factors contributing to the patient’s acid–base status beyond sodium, chloride, lactate, and bicarbonate. Regarding the question of why the patient had a primary respiratory alkalosis, she was not hypoxemic to suggest a primary pulmonary cause, and she did not have evidence of salicylate toxicity. In this case, the respiratory alkalosis was likely due to hyperventilation, perhaps related to an increased drive to excrete acetone. Dr. Nadel: You had mentioned obtaining imaging studies. What were those results? Dr. David Curley: By the time imaging results were available, I had assumed care of the patient from my colleague. A portable chest X-ray study showed proper positioning of the endotracheal tube as well as a left lung base opacity consistent with atelectasis or aspiration. CT of the abdomen was unremarkable and a CT scan of the head showed no acute abnormalities. None of these findings were thought to explain the patient’s symptoms. The patient was admitted to the ICU. Dr. James K. Takayesu: This patient seems to have had a toxic ingestion. Can you describe how you thought about this? Dr. Curley: This patient had an anion gap of 32 and a lactate of 14.6 mmol/L. She was hyperadrenergic. We recognized that, in addition to the prominent respiratory alkalosis, she also had a metabolic acidosis and so we considered the various causes of this. A frequently taught mnemonic is MUDPILES. We quickly discounted uremia due to a normal blood urea nitrogen level, diabetic ketoacidosis with an unimpressively elevated serum glucose, isoniazid as it was not a medication to which she was thought to have access, and salicylate with a negative test. In particular, with a presumed toxic ingestion, one must consider the toxic alcohols: methanol, ethylene glycol, and propylene gly-
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col. Methanol is metabolized to formaldehyde and formic acid, mainly in the liver. Ethylene glycol is metabolized to glycolic acid and oxalic acid, which may cause CNS depression and seizures. Longer-term toxic effects of these metabolites include calcium oxalate crystal formation in the kidney and resulting acute kidney injury. Propylene glycol is a food and drug additive and less available to the general public. However, it is metabolized into pyruvic acid, acetic acid, lactic acid, and propionaldehyde. The initial effects of propylene glycol overdose are also CNS depression. Additionally, this patient had an elevated osmolar gap. Taken together, the patient was empirically treated with fomepizole, an alcohol dehydrogenase inhibitor. It is important to treat early with fomepizole, as it prevents the formation of toxic metabolites. Once the metabolism has already occurred, there is no benefit to this antidote. Cyanide must always be considered in the setting of a very elevated lactate. However, this patient’s clinical picture was not one of cyanide poisoning. Finally, it is extremely important to consider toxic co-ingestions such as acetaminophen whenever ingestion is suspected. The consequences of missing and not treating such a coingestion could be severe, even if you are able to steward the patient through their initial insult. Dr. Wendy Macias-Konstantopoulos: This patient seems to have been quite agitated. Did she fit into a toxidrome that helped aid in the diagnosis? Dr. Curley: Perhaps one of the most common toxidromes we see in the ED is that of sympathomimetics. Classic features include anxiety, diaphoresis, hyperreflexia, mydriasis, piloerection, hypertension, tachycardia, and seizures. Common causes are agents such as amphetamines, cocaine, and pseudoephedrine. Although this patient did not fit into any easily identifiable toxidrome, this was probably the closest to her presentation. Other common toxidromes to consider when a patient arrives include anticholinergic (delirium, anhydrosis, mydriasis, flushing, hyperthermia, seizures, and dysrhythmias), cholinergic (diaphoresis, urination, miosis, bradycardia, bronchorrhea, emesis, lacrimation, and salivation), opioid (respiratory depression, hypotension, miosis, bradycardia, seizure, and coma), and salicylism (tinnitus, hyperpnea, depressed mental status, and delirium). For various reasons mentioned above, our patient did not fit any of these additional syndromes. Dr. Brown: Can you tell us about the remainder of this patient’s course? Dr. Curley: Shortly after admission to the medical ICU, the patient’s husband came to the hospital and was able to provide additional history. The patient had reportedly been consuming up to a liter of vodka daily. However, she had run out of liquor approximately 3 days prior to this hospital admission and had begun
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drinking other household items such as NyQuil and Listerine. The family found an empty bottle of nail polish remover (which contains acetone) in her bed on the day of this presentation. Given this additional history, fomepizole was discontinued in the ICU. She was started on phenobarbital for alcohol withdrawal and subsequently extubated. The initial heart rhythm was considered most likely to be a supraventricular re-entrant tachycardia, likely in response to physiologic stress, adrenergic tone, toxic ingestion, and alcohol withdrawal. She had a transthoracic echocardiogram that revealed a structurally normal heart. She was treated with beta-blockade for persistent sinus tachycardia. The patient was seen by Psychiatry, who believed her presentation was most likely the result of alcohol dependence rather than an intent to self harm. Phenobarbital was tapered and the patient was discharged on hospital day 5. She has since followed up in clinic and is doing well. Dr. Peak: Is there anything we should know in particular about the potential effects and needed treatment of acute acetone ingestion? Dr. Curley: Strong medical literature data on human acetone toxicity are lacking, although case reports shed some light on typical presentations. A report in 1988 of a pediatric ingestion of acetone described respiratory depression, CNS depression, hyperglycemia, acidosis, and hypotension (2). These symptoms all resolved with supportive care. In its toxicologic profile of acetone, the Agency for Toxic Substances and Disease Registry (ATSDR) reported an oral LD50 of approximately 1.7–9.9 g/kg in rat studies (3). The no-observedadverse-effects level was reported as 0.8–12 mg/kg. Metabolically, acetone is either excreted unchanged via the kidneys or lungs or it is metabolized through multiple
J. E. Slutzman et al.
pathways to end products including glucose, D-lactate, L-lactate, acetate, and formate. Dr. Nagurney: Because this patient presented with agitation rather than CNS depression, and tachypnea rather than respiratory depression, do you think the acetone ingestion was complicated by another factor? Dr. Curley: Yes, we do. It is likely that this patient was suffering from acute alcohol withdrawal symptoms, perhaps inducing her to drink products that were on hand. Alcohol withdrawal syndrome is a hyperadrenergic state, which contributed to this patient’s tachydysrhythmia, mydriasis, and likely seizure at home (4). In fact, her lab values can be explained by these two opposing toxicologic effects affecting her simultaneously. Dr. Nadel: What are your take-home points from this case? Dr. Curley: Focusing on initial resuscitative measures to support a patient is key, to be followed by careful interpretation of lab and imaging findings to exclude or include parts of your differential diagnosis. Ultimately, though, it was the history provided by the patient’s husband that made the final diagnosis. REFERENCES 1. Green M, Heddle B, Dassen W, et al. Value of QRS alteration in determining the site of origin of narrow QRS supraventricular tachycardia. Circulation 1983;68:368–73. 2. Gamis A, Wasserman G. Acute acetone intoxication in a pediatric patient. Pediatr Emerg Care 1988;4:24–6. 3. Agency for Toxic Substances and Disease Registry, Public Health Service. Toxicological profile for acetone. Atlanta, GA: U.S. Department of Health and Human Services; 1994. 4. Awissi D, Lebrun G, Coursin D, Riker R, Skrobik Y. Alcohol withdrawal and delirium tremens in the critically ill: a systematic review and commentary. Intensive Care Med 2013;39:16–30.