December 2013 Critical Care Case of the Month: I Don’t Have a Drinking Problem

Robert Raschke MD

Elijah Poulos MD

Adam Bosak MD

Critical Care Medicine

Banner Good Samaritan Medical Center

Phoenix, AZ

History of Present Illness

A 69-year-old male retired diabetic police officer was admitted to the ICU with intractable vomiting, severe abdominal pain and acute blindness. About a week prior, he suffered urinary frequency and was prescribed ciprofloxacin at urgent care with a presumptive diagnosis of urinary tract infection.  Over the course of the week his urinary frequency resolved and he became anuric, he developed progressively worsening nausea and eventually vomiting to the point that he was unable to keep anything down, and severe bilateral lower abdominal and pelvic pain.    His wife and son actually forced him into the ER when he became blind the day of admission. He denied fever, dysuria, cough and headache.   In our emergency room he was noted to be in moderate distress with tachycardia, tachypnea, hyperpnoea and completely blind in both eyes unable to discern even simple shadows.

PMH, SH, FH

The patient is a retired police officer with a past medical history of diabetes mellitus and benign prostatic hypertrophy.  The patient denied alcohol, tobacco, or illicit drug use. He works out at a local gym almost daily since being diagnosed with diabetes a couple of years ago.

Medications

• Glipizide
• Metformin
• Tamsulosin

Physical Exam

Blood pressure160/95 mmHg with a heart rate of 110, respiratory rate 35, SpO2 99% on 2 lpm nasal cannula, and temp 36.0° C.  He appeared uncomfortable and moderately distressed, lethargic but arousable with GCS 13. He was able to briefly answer simple questions. His eyes were conjugate, but did not track nor fix on objects placed in front of his eyes, and he could vaguely discern the light of a bright flashlight shined into both eyes. His pupils were 3-4 mm and fixed, with no light reflex elicitable, even with magnified examination of the pupil using an ophthalmoscope.  On fundoscopic exam his discs were flat, and there were no hemorrhages or other lesions seen.  He was tachycardic but regular with normal heart tones, and a bedside echocardiogram showed good left ventricular function.  He had Kussmaul breathing with an odor of ketones and clear lungs. The lower abdomen was distended and tender, and a Foley catheter insertion returned 2 liters of yellow urine which resolved his abdominal pains.  He had no peripheral edema and his hands were cool.  The rest of his physical examination was unremarkable.

Laboratory Evaluation

Initial laboratory evaluation included a white blood count 24.3 K/mm3 with 79% segmented neutrophils and no bands, hemoglobin 14.7 g/dL; sodium 138 mmol/L;  potassium 5.1 mmol/L; chloride 92 mmol/L; and CO₂ 4 mmol/L, yielding an anion gap of 44 when corrected.  His BUN was 116 mg/dL; creatinine of 7.7 mg/dL.  A venous blood gas showed a pH 6.77 pCO₂ 17 mmHg; pO₂ 73 mmHg; bicarbonate of 3 mmol/L. Urinalysis showed negative leukocyte esterase, 1-5 leukocytes per HPF, glycosuria and ketonuria.

Radiology Evaluation

Admission chest x-ray is in Figure 1. 

Figure 1. Admitting chest radiograph.

Computerized tomography of the abdomen showed no urinary tract obstruction (was performed after the Foley catheter was placed) and no other significant findings. Piperacillin/tazobactam and gentamicin were started for possible urinary tract infection with sepsis.

Which of the following is the best fits the clinical presentation explaining both his metabolic abnormalities and blindness? (click on correct answer to move to next panel)

1. Acute renal failure
2. Alcoholic ketoacidosis
3. Diabetic ketoacidosis
4. Ethylene glycol ingestion
5. Methanol ingestion

Reference as: Raschke RA, Poulos E, Bosak A. December 2013 critical care case of the month: I don't have a drinking problem. Southwest J Pulm Crit Care. 2013;7(6):328-35. doi: http://dx.doi.org/10.13175/swjpcc141-13 PDF

Ultrasound for Critical Care Physicians: Atypical Headache

A 76 year old woman presented with complaints of a new onset of headache especially on the right. Brain CT scan and MRI were unremarkable. Her erythrocyte sedimentation rate was markedly elevated. An ultrasound of the chest was performed (Figures 1 and 2).

Figure 1. Long axis view through the aortic valve area (movie has been slowed).

Figure 2. Transverse view through the aorta (movie has been slowed).

What does the ultrasound show?

1. Aortic aneurysm
2. Aortic insufficiency
3. Aortic stenosis
4. Aortic wall thickening
5. 1 and 2
6. 1 and 4
7. 2 and 4

Reference as: Gotway MB. Ultrasound for critical care physicians: atypical headache. Southwest J Pulm Crit Care. 2013;7(5):289-90. doi: http://dx.doi.org/10.13175/swjpcc125-13 PDF

November 2013 Critical Care Case of the Month: A Series of Unfortunate Infections

Kenneth K. Sakata, MD

Karen L. Sapienza, MD

Lewis J. Wesselius, MD 

Department of Pulmonary Medicine

Mayo Clinic Arizona

Scottsdale, AZ

History of Present Illness

A 22 year old man was admitted with fever for 2 weeks. He had a history of acute lymphocytic leukemia (ALL) and had received a stem cell transplant in (SCT) in May 2013.

PMH, SH, FH

Other than the ALL and STC transplant there was no significant PMH, SH, or FH. The STC was uneventful.

Physical Examination

T 38.6°C with a pulse of 110 beats/min. Otherwise the physical examination was unremarkable.

CT scan

A CT scan of the thorax was performed in a search for the source of the fever (Figure 1).

Figure 1. Admission thoracic CT scan showing an abnormality. The remainder of the CT scan was unremarkable.

Which of the following best describes the CT abnormality?

1. Chest wall abnormality in the left chest
2. Focal area of consolidation in the left lung
3. Focal area of consolidation in the right lung
4. Mass in the left lung
5. Mass in the right lung

Reference as: Sakata KK, Sapienza KL, Wesselius LJ. November 2013 pulmonary case of the month: a series of unfortunate infections. Southwest J Pulm Crit Care. 2013;7(5):280-8. doi: http://dx.doi.org/10.13175/swjpcc139-13 PDF

Fat Embolism Syndrome: Improved Diagnosis Through the Use of Bedside Echocardiography

Douglas T. Summerfield, MD

Kelly Cawcutt, MD

Robert Van Demark, MD

Matthew J. Ritter, MD

Departments of Anesthesia and Pulmonary/Critical Care Medicine

Mayo Clinic

Rochester, MN

Case Report

A 77 year old female with a past medical history of dementia, chronic atrial fibrillation requiring anticoagulation, hypertension, biventricular congestive heart failure with a preserved left ventricular ejection fraction, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD) presented to the emergency room after she sustained a ground level fall while sitting in a chair. The patient reportedly fell asleep while sitting at the kitchen table, and subsequently fell to her right side. According to witnesses, she did not strike her head, and there was no observed loss of consciousness. As part of her initial evaluation, at an outside hospital, radiographs of the pelvis, hip, and knee were obtained. These identified a definitive right superior pubic ramus fracture with inferior displacement and a questionable fracture of the right femoral neck. Shortly thereafter, the patient was transferred to our hospital for further management. On exam, the patient had a painful right hip limiting active motion and her right lower extremity was neurovascularly intact without paresthesias or dysesthesias. The remainder of the exam was unremarkable. In the emergency room, a repeat radiograph showed no evidence of a right femur fracture. Later in the evening a CT scan of the pelvis with intravenous contrast showed acute fractures through the right superior and inferior pubic rami with associated hematoma. Multiple tiny bony fragments were noted adjacent to the superior pubic ramus fracture (Figure 1).

Figure 1. CT scan demonstrating acute fractures through the superior and inferior pubic rami with associated hematoma. Multiple tiny bone fragments are adjacent to the superior pubic ramus fracture.

The CT did not show an apparent femur fracture. MRI of the pelvis and hip were ordered to assess for a femoral fracture; however this was not obtained secondary to patient confusion thus no quality diagnostic images were produced. The orthopedic service concluded that surgery was not required for the stable, type 1 lateral compression injury that resulted from the fall.

The patient was admitted to a general medicine floor for non-surgical management which included weight bearing as tolerated as well as therapy with physical medicine and rehabilitation. On admission, her vital signs were stable, including a heart rate of 89, blood pressure of 159/89, respirations of 20, with the exception of her peripheral oxygen saturation which was 89% on room air. Over the next several hospital days, she continued to have low oxygen saturations, began requiring fluid boluses to maintain an adequate mean arterial blood pressure (secondary to systolic blood pressure falling to the 70-80mmHg range intermittently) and she developed acute kidney injury with her creatinine increasing to 4.2 from her baseline of 1.1.  Nephrology was consulted to evaluate the acute kidney injury and their impression was acute renal failure secondary to contrast administration for the initial CT scan, in the setting of chronic spironolactone and furosemide use. The patient’s mental status remained altered, her speech although typically understandable was non-coherent, and she remained bed-bound. Due to her underlying dementia, her baseline mental status was difficult to determine and this combined with her opioids for pain control were felt to contribute to her mental status.

During her first dialysis session, the patient developed hypotension and hypoxemia which necessitated a rapid response call and transfer to the intensive care unit (ICU). The impression at the time of transfer to the ICU was septic shock with multi-organ dysfunction syndrome, presumably from a urinary source. The initial exam by the ICU team demonstrated what was thought to be considerable acute mental status change with agitation and moaning, hypotension, hypoxemia, and continued renal failure. Further review of her hospital course revealed that these changes had slowly been progressing since admission. Stabilization in the ICU included placement of a right internal jugular central venous catheter, blood pressure support with vasopressors, as well as intubation and high level of ventilatory support, including inhaled alprostadil, for severe hypoxemic respiratory failure. In addition, she was also placed on continuous renal replacement therapy.

In order to better assess the patient’s fluid status, the service fellow assessed the vena cava with the bedside ultrasound. While observing the collapsibility of the IVC, small hyperechoic spheres were observed traveling through the IVC proximally towards the right heart. A subcostal window focusing on the right ventricle demonstrated the same hyperechoic spheres whirling within the right ventricle. These same spheres were seen in both the four chamber view (Figure 2), as well as the short axis view and were present for several hours.

Figure 2. Four chambered view revealing right ventricular bowing as well as small hyperechoic spheres present in the right ventricle and atria.

Two hours later, a formal bedside echocardiogram was performed to evaluate the right heart structure and function. The estimated right ventricular systolic pressure was at 70 mm Hg, indicating severe pulmonary hypertension. The right ventricle was enlarged, and there was severe tricuspid regurgitation. Again there continued to be small hyperechoic spheres within her right ventricle as well as her right atria. Per the formal cardiologist reading, these were consistent with fat emboli. Further laboratory evaluation, including the presence of urinary fat, helped confirm the diagnosis of fat emboli syndrome.

Supportive care was continued, but without obvious improvement. After a family care conference, she was transitioned to palliative care and died.

Background

Fat emboli (FE) and fat emboli syndrome (FES) have been described clinically and pathologically since the 1860’s. Early work by Zenker in 1862 first described the pathologic significance of fat embolism with the link of fat to bone marrow release during fractures was discovered by Wagner in 1865. Despite the 150 years since its discovery, the diagnosis of Fat Embolism remains elusive. FE is quite common with the presence of intravascular pulmonary fat seen in greater than 90% of patients with skeletal trauma at autopsy (1). However, the presence of pulmonary fat alone does not necessarily mean the patient will develop FES. In a case series of 51 medical and surgical ICU patients, FE was identified in 28 (51%) of patients, none of whom had classic manifestations of FES (2).

The three major components of FES have classically consisted of the triad of petechial rash, progressive respiratory failure, and neurologic deterioration. The incidence following orthopedic procedures ranges from 0.25% to 35% (3). The wide variation of the reported incidence may in part be due to the fact that FES can affect almost every organ system and the classic symptoms are only present either transiently or in varying degrees, and may not manifest for 12-72 hours after the initial insult (4). The patient we present represents both the lack of the classic triad and the delayed onset of signs and symptoms, illustrating the elusiveness of the diagnosis.

Of the major clinical criteria, the cardio-pulmonary symptoms are the most clinically significant. Symptoms occur in up to 75% of patients with FES and range from mild hypoxemia to ARDS and/or acute cor pulmonale. The timing of symptoms may coincide with manipulation of a fracture, and there have been numerous reports of this occurring intraoperatively with direct visualization of fat emboli seen on trans-esophageal echo (TEE) (5-8).

The classic petechial rash, which was not noted in our patient, is typically seen on the upper anterior torso, oral mucosa, and conjunctiva. It is usually resolved within 24 hours and has been attributed to dermal vessel engorgement, endothelial fragility, and platelet damage all from the release of free fatty acids (9). The clinical manifestation of this “classic” finding varies widely and has been reported in 25-95% of the cases (4, 10).

Neurologic dysfunction can range from headache to seizure and coma and is thought to be secondary to cerebral edema due to multifactorial insults. These neurologic changes are seen in up to 86% of patients, and on MRI produce multiple small, non-confluent hyper intensities that appear within 30 minutes of injury. The number and size correlate to GCS, and subsequently reversal of the lesions is seen during neurologic recovery. (11,12).

Temporary CNS dysfunction usually occurs 24-72 hours after initial injury and acute loss of consciousness immediately post-operatively has been documented. Of note, this loss of consciousness may not be a catastrophic event. In a case report by Nandi et al., a patient with acute loss of consciousness made full neurologic recovery within four hours (13). In the retina, direct evidence of FE and FES manifests as cotton-wool spots and flame-like hemorrhages (1). However these findings are only detected in 50% of patient with FES (14)

FES also affects the hematological system, producing anemia and thrombocytopenia 37% and 67% of the time, respectively (15, 16). Thrombocytopenia is correlated to an increased A-a gradient, which Akhtar et al. noted that some clinicians include this finding in the criteria to diagnose FES (1).

Diagnosis

Given the broad and varying manifestations of FES, others have broadened the criteria. The Lindeque criteria require a femur fracture. The FES Index is a scoring system which includes vitals, radiographic findings, and blood gas results. Weisz and colleagues include laboratory values such as fat macroglobulenemia and serum lipid changes. Miller and colleagues (17) even proposed an autopsy diagnosis using histopathic samples. The most widely used criteria are set forth by Gurd and Wilson and require two out of three major criteria be met, or one major plus four out of five minor criteria. Major criteria include pulmonary symptoms, petechial rash, and neurological symptoms. Minor criteria include pyrexia, tachycardia, jaundice, platelet drop by >50%, elevated ESR, retinal changes, renal dysfunction, presence of urinary or sputum fat, and fat macroglobulinemia (1). Of note, none of the proposed diagnostic criteria include direct visualization of fat emboli via ultrasound or echocardiography (18-22) (Table 1).

Table 1: Gurd's Criteria for Diagnosis of FES

Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;52(4):732-7. [PubMed]

Mechanism

Two theories explain the systemic symptoms seen in FES. The mechanical theory describes how intramedullary free fat is released into the venous circulation directly from the fracture site or from increased intramedullary pressure during an orthopedic procedure. The basis for the theory is that the fat particles produce mechanical obstruction. However, not all fat emboli translocated into the circulation are harmful. It is estimated that fat particles larger than 8 μm embolize (23-25). As they accumulate in the lungs, aggregates larger than 20 μm occlude the pulmonary vasculature (26). Particles 7-10 μm particles can cross pulmonary capillary beds to affect the skin, brain, and kidneys. On a larger scale, the embolized free fatty acids produce ischemia and the subsequent release of inflammatory markers (27). The mechanism of this systemic spread beyond the pulmonary capillaries is not well understood. Patients without a patent foramen ovale or proven pulmonary shunt develop FES (28). Interestingly enough, other patients with a large fat emboli burden in the pulmonary microvasculature have not progressed to FES (29). One possible explanation for this may be elevated right-sided pressures force pulmonary fat into systemic circulation (1).

The biochemical theory has also been proposed to explain the systemic organ damage. The mechanism describes that enzymatic degradation of fat particles in the blood stream brings about the release of free fatty acids (FFA) (30, 31). FFA and the toxic intermediaries then cause direct injury on the lung and other organs. The fact that many of the symptoms are seen much later than the initial injury would support the Biochemical Theory. This theory also has an obstructive component to it as it recognizes that large fat particles coalesce to obstruct pulmonary capillary beds (11).

Discussion

Fat emboli syndrome is a rare and difficult clinical diagnosis. Currently there is no diagnostic test for FES and even the reported incidence is quite variable. The wide clinical presentation of FES makes the diagnosis challenge, and classic pulmonary involvement does not always occur (31). Furthermore, the symptoms overlap with other illness such as infection, as it did in this patient who was initially thought to be septic. The delayed onset of symptoms may further confound its identification. Finally, the traditional criteria used to diagnosis FES are variable depending on which source is referenced. Case-in-point is the Lindque criteria which require the presence of a femur fracture. By this requirement the patient presented in this case would not have been diagnosed with FES as she presented with a pelvic fracture.

The patient in this case was likely suffering from undiagnosed FES from the time of her admission. Since it did not present in the classic fashion, her progressive respiratory failure and neurologic deterioration were incorrectly attributed to congestive heart failure and opioid administration.

In this patient, the diagnosis of FE was somewhat unexpected, although it was within the differential. For this case the implementation of bedside ultrasound proved critical to the correct diagnosis and subsequent outcome. Instead of following other possible diagnoses and treatment options such as sepsis in this tachycardic, hypotensive patient, supportive care was employed with the diagnosis of fat embolism in mind.

The use of ultrasound imaging is not well studied for the diagnosis of FES, however it may provide an additional tool for making this difficult diagnosis when the classic triad of rash, cardiopulmonary symptoms, and neurologic changes is not seen or is in doubt. When used to evaluate for cardiogenic causes of acute hypotension, bedside cardiac ultrasound may reveal findings suggestive of FES, as it did in this case.

Review of the literature (5-8) confirms similar echogenic findings from fat emboli as seen by TEE intraoperatively during orthopedic procedures. However, similar spheres can be seen in a number of other instances. Infusion of blood products, such as packed red blood cells, may create similar acoustic images. No blood products had been given to the patient at the time of the bedside ultrasound. Additionally cardiologists have traditionally used agitated saline to look for patent foramen ovale. This and air embolism after placement of a central venous catheter can both produce similar images. In this case the emboli were seen traveling through the inferior vena cava, inferior and distal to the right side of the heart. The right internal jugular catheter would not have showered air emboli to that location, additionally once these were seen circulating in the right ventricle, the first action performed was to ensure all ports on the central line were secure. Given that these hyperechoic spheres were present for hours, air emboli would be less likely to be the underlying etiology. The images were later seen during the formal cardiac echo, and again validated by the cardiologist as being consistent with fat emboli.

To our knowledge this is the first case report of critical care bedside echocardiography (BE), assisting with the diagnosis of fat emboli syndrome. This is in contrast to TEE which has been used to diagnose FE and presumed FES in hemodynamically unstable patients in the operating room (5-8).

BE is attractive as it requires less training than TEE and can be repeated at the bedside as the clinical picture changes. By itself BE cannot differentiate FE from FES, but since the practitioner using it is presumably familiar with the patient’s condition, it can be used to augment the diagnosis when other findings are also suggestive of FE.

It has been suggested that a basic level of expertise in bedside echocardiography can be achieved by the non-cardiologist in as little as 12 hours of didactic and hands-on teaching. Given this amount of training, the novice ultrasonographer should be able to identify severe left or right ventricular failure, pericardial effusions, regional wall motion abnormalities, gross valvular abnormalities, and volume status by assessing the size and collapsibility of the inferior vena cava (32-37). Potentially, based on this case, the list could include FE with FES in the correct clinical context, pending further clinical validation.

In conclusion, this is the first reported case of bedside ultrasonography assisting in the diagnosis of FES in the ICU. The case illustrates the diagnostic challenge of FE and FES and also highlights the potential utility of bedside ultrasonography as a diagnostic tool.

References

1. Akhtar S. Fat Embolism. Anesthesiology Clinics. 2009;27:533-50. [CrossRef] [PubMed] 
2. Gitin TA, Seidel T, Cera PJ, Glidewell OJ, Smith JL. Pulmonary microvascular fat: The significance? Critical Care Medicine. 1993;21(5):673-7. [CrossRef] [PubMed] 
3. Raza SS, Noheria A, Kesman RL. 21-year-old man with chest pain, respiratory distress, and altered mental status. Mayo Clin Proc. 2011;86(5):e29-e32. [CrossRef] [PubMed]
4. Capan LM, Miller SM, Patel KP. Fat embolism. Anesthesiol Clin North America. 1993;11:25–54.
5. Shine TS, Feinglass NG, Leone BJ, Murray PM. Transesophageal echocardiography for detection of propagating, massive emboli during prosthetic hip fracture surgery. Iowa Orthop J. 2010;30:211-4. [PubMed] 
6. Heinrich H, Kremer P, Winter H, Wörsdorfer O, Ahnefeld FW. Transesophageal 2-dimensional echocardiography in hip endoprostheses. Anaesthesist. 1985;34(3):118-23. [PubMed] 
7. Pell AC, Christie J, Keating JF, Sutherland GR. The detection of fat embolism by transoesophageal echocardiography during reamed intramedullary nailing. A study of 24 patients with femoral and tibialfractures. J Bone Joint Surg Br 1993; 75:921-5. [PubMed]
8. Christie J, Robinson CM, Pell AC, McBirnie J, Burnett R. Transcardiac echocardiography during invasive intramedullary procedures. J BoneJoint Surg Br 1995;77:450-5. [PubMed]
9. Pazell JA, Peltier LF. Experience with sixty-three patients with fat embolism. Surg Gynecol Obstet 1972;135(1):77–80. [PubMed] 
10. Gossling HR, Pellegrini VD Jr. Fat embolism syndrome: a review of the pathophysiology and physiological basis of treatment. Clin Orthop Relat Res. 1982;165:68–82. [PubMed] 
11. Shaikh N, Parchani A, Bhat V, Kattren MA. Fat embolism syndrome: Clinical and imaging considerations: Case report and review of literature. Indian J Crit Care Med. 2008;12(1):32-6. [CrossRef] [PubMed]
12. Butteriss DJ, Mahad D, Soh C, Walls T, Weir D, Birchall D. Reversible cytotoxic cerebral edema incerebral fat embolism. AJNR Am J Neuroradiol. 2006;27(3):620-3. [PubMed]
13. Nandi R, Krishna HM, Shetty N. Fat embolism syndrome presenting as sudden loss of consciousness. J Anaesthesiol Clin Pharmacol. 2010;26(4):549-50. [Pubmed]
14. Adams CB. The retinal manifestations of fat embolism. Injury. 1971;2(3):221-4. [CrossRef]
15. Mellor A, Soni N. Fat embolism. Anaesthesia. 2001;56:145-54. [CrossRef]
16. Bulger EM, Smith DG, Maier RV, Jurkovich GJ. Fat embolism syndrome. A 10-year review. Arch Surg. 1997;132:435-9. [CrossRef] [PubMed]  
17. Miller P, Prahlow JA. Autopsy diagnosis of fat emboli syndrome. Am J Forensic Med Pathol. 2011;32(3):291-9. [CrossRef] [PubMed] 
18. Gurd AR. Fat embolism: an aid to diagnosis. J Bone Joint Surg Br. 1970;52(4):732-7. [PubMed]
19. Gurd AR, Wilson RI. The fat embolism syndrome. J Bone Joint Surg Br 1974;56(3):408-16.
20. Weisz GM, Rang M, Salter RB. Posttraumatic fat embolism in children: review of the literature and of experience in the Hospital for Sick Children, Toronto. J Trauma. 1973;13:529-34. [CrossRef] [PubMed] 
21. Lindeque BG, Schoeman HS, Dommisse GF, Boeyens MC, Vlok AL. Fat embolism and the fat embolism syndrome. A double-blind therapeutic study. J Bone Joint Surg Br 1987;69(1):128-31. [PubMed] 
22. Schonfeld SA, Ploysongsang Y, DiLisio R, Crissman JD, Miller E, Hammerschmidt DE, Jacob HS. Fat embolism prophylaxis with corticosteroids. A prospective study in high-risk patients. Ann Intern Med. 1983;99:438-43. [CrossRef] [PubMed] 
23. Pell AC, Hughes D, Keating J, Christie J, Busuttil A, Sutherland GR. Fulminating fat embolism syndrome caused by paradoxical embolism through a patent foramen ovale. N Engl J Med. 1993;329:926-9. [CrossRef] [PubMed] 
24. Argenziano M. The incidental finding of a patent foramen ovale during cardiac surgery: should it always be repaired? Anesth Analg. 2007;105:611-2. [CrossRef] [PubMed] 
25. Emson HE. Fat embolism studied in 100 patients dying after injury. J Clin Pathol. 1958;11(1):28-35. [CrossRef] [PubMed]
26. Batra P. The fat embolism syndrome. J Thorac Imaging. 1987;2(3):12–17. [CrossRef] [PubMed] 
27. Meyer N, Pennington WT, Dewitt D, Schmeling GJ. Isolated cerebral fat emboli syndrome in multiply injured patients: a review of three casesand the literature. J Trauma. 2007;63:1395-1402. [PubMed] 
28. Nijsten MW, Hamer JP, ten Duis HJ, Posma JL. Fat embolism and patent foramen ovale [letter]. Lancet 1989;1(8649):1271. [CrossRef]
29. Aoki N, Soma K, Shindo M, Kurosawa T, Ohwada T. Evaluation of potential fat emboli during placement of intramedullary nails after orthopedic fractures. Chest. 1998;113(1):178-81. [CrossRef] [PubMed] 
30. Talbot M, Schemitsch EH. Fat embolism syndrome: history, definition, epidemiology. Injury. 2006;37S:S3-S7. [CrossRef] [PubMed] 
31. Levy D. The fat embolism syndrome. A review. Clin Orthop Relat Res. 1990;261:281-6. [PubMed] 
32. Vignon P, Mücke F, Bellec F, Marin B, Croce J, Brouqui T, Palobart C, Senges P, Truffy C, Wachmann A, Dugard A, Amiel JB. Basic critical care echocardiography: Validation of a curriculum dedicated to noncardiologist residents. Crit Care Med. Apr 2011;39(4):636-42. [CrossRef] [PubMed] 
33. Vignon P, Dugard A, Abraham J, Belcour D, Gondran G, Pepino F, Marin B, François B, Gastinne H. Focused training for goal-oriented hand-held echocardiography performed by noncardiologist residents in the intensive care unit. Intensive Care Med. 2007;33(10):1795-99. [CrossRef] [PubMed] 
34. Manasia AR, Nagaraj HM, Kodali RB, Croft LB, Oropello JM, Kohli-Seth R, Leibowitz AB, DelGiudice R, Hufanda JF, Benjamin E, Goldman ME. Feasibility and potential clinical utility of goal-directed transthoracic echocardiography performed by noncardiologist intensivists using a small hand-carried device (SonoHeart) in critically ill patients. J Cardiothorac Vasc Anesth. 2005;19(2):155-9. [CrossRef] [PubMed] 
35. Melamed R, Sprenkle MD, Ulstad VK, Herzog CA, Leatherman JW. Assessment of left ventricular function by intensivists using hand-held echocardiography. Chest. Jun 2009;135(6):1416-20. [CrossRef] [PubMed] 
36. Vignon P, Chastagner C, François B, Martaillé JF, Normand S, Bonnivard M, Gastinne H. Diagnostic ability of hand-held echocardiography in ventilated critically ill patients. Crit Care. 2003;7(5):R84-91. [CrossRef] [PubMed]
37. Mayo PH, Beaulieu Y, Doelken P, Feller-Kopman D, Harrod C, Kaplan A, Oropello J, Vieillard-Baron A, Axler O, Lichtenstein D, Maury E, Slama M, Vignon P. American College of Chest Physicians/La Societe de Reanimation de Langue Francaise statement on competence in critical care ultrasonography. Chest. 2009;135(4):1050-60. [CrossRef] [PubMed]

Reference as: Summerfield DT, Cawcutt K, Van Demark R, Ritter MJ. Fat embolism syndrome: improved diagnosis through the use of bedside echocardiography. Southwest J Pulm Crit Care. 2013;7(4):255-64. doi: http://dx.doi.org/10.13175/swjpcc109-13 PDF

Refractory Cardiogenic Shock

Bhupinder Natt, MD (bnatt@deptofmed.arizona.edu)

Tauseef Afaq Siddiqi, MD (tsiddiqi@deptofmed.arizona.edu)

Jarrod Mosier, MD (jmosier@aemrc.arizona.edu)

Yuval Raz, MD (yraz@deptofmed.arizona.edu)

Department of Medicine, Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, University of Arizona, Tucson, AZ

Abstract

We present a case of refractory cardiogenic shock secondary to myxedema crises that was treated successfully with thyroid hormone replacement.

Case Presentation

History of Present Illness

A 62-year-old woman with past medical history significant only for hypothyroidism was seen in the emergency department (ED) after a fall at home. On further evaluation, the patient’s husband reported history consistent with deteriorating mental function as evident by speech alteration, inability to operate home appliances like the coffeemaker and gradually worsening generalized weakness. She was recently seen at an outside hospital the week previous to this admission and given a prescription for furosemide for pedal edema.

ED evaluation showed her to be lethargic, disoriented with progressively deteriorating mentation, with hypothermia and bradycardia. Her progressive decline in mentation led to endotracheal intubation for airway protection. The patient was started on vasopressors due to post-intubation hypotension and transferred to the Medical Intensive Care Unit (MICU).

Vitals and Physical Exam

Vitals upon presentation to ED: Temperature 29^o Celsius; Heart Rate 42 bpm; Blood Pressuren107/79 mm Hg; Respiratory Rate 14/min; SpO2 97 % on Room Air.

Vitals upon arrival in MICU: Temperature of 29^o Celsius; Heart Rate 43 bpm; Blood Pressure 111/57 mmHg; Respiratory Rate of 10/min; SpO2 100% on mechanical ventilation;

Neurologically, she was sedated with no obvious localizing signs. Skin exam revealed a sutured scalp lesion and scattered abrasion on arms. Cardiopulmonary exam was significant only for bradycardia, which was determined to be sinus rhythm by the electrocardiogram (EKG). Other system examination was significant only for 2+ non-pitting edema of upper and lower extremities.

Laboratory and Radiology Data

CBC: White Cell Count 8.4x1000/microL; Hemoglobin 9.5 g/dL; MCV 100 fL; Platelets 82x1000/microL.

Electrolytes and Metabolic Panel: Sodium 134 mMol/L; Potassium 4.2 mMol/L; Chloride 97 mMol/L; Bicarbonate 26 mMol/L; Urea Nitrogen 38 mg/dL; Creatinine 0.9 mg/dL. Glucose 78 mg/dL; Calcium 9.6 mg/dL.

Total Protein 6.3 g/dL; Albumin 3.7 g/dL; Bilirubin 0.7 mg/dL; Alkaline Phosphate 104 IU/L; ALT 72 IU/L; AST 158 IU/L; TSH 36.1 uIU/mL; Thyroxine 0.8 ng/dL; Free T3 1.2 pg/mL (Normal 2.4-4.2 pg/mL); Cortisol 20.3 mcg/dL.

ABG: pH 7.52; PaCO2 34; PaO2 166; HCO3 28; SaO2 97.6 % on 50% FiO2.

Urine Analysis: Negative.

Urine Drug Screen: Negative.

Chest X-Ray: Emphysematous changes with no acute cardiopulmonary process.

Non-contrast CT of the head and cervical spine: Unremarkable except scalp hematoma.

EKG at Presentation

MICU Course

After initial stabilization of blood pressure in ED; receiving four liters of intravenous fluids; and norepinephrine infusion at increasing doses, she was transferred to MICU. She required two more liters of crystalloids, vasopressin and increasing doses of norepinephrine, epinephrine, phenylephrine and dobutamine infusions. Corticosteroid was added for refractory shock. She also received first dose of broad-spectrum antimicrobials in ED.

Two hours after arrival to the MICU, seven hours post presentation to the ED; a Swan-Ganz pulmonary artery catheter was placed. The values obtained from the Swan-Ganz catheter are reported in table 1. 

These values were obtained seven hours into admission, while the patient was being actively rewarmed, treated with a total of six liters (L) of crystalloid solutions and on norepinephrine at 13 mcg/min and dobutamine at 5 mcg/kg/min.

The patient remained hypotensive and sequentially, within hours, multiple vasopressors and inotropic agents were required. Table 2 reports the vitals and values off the Swan-Ganz catheter 12 hours after initial placement, when the patient is being actively rewarmed, treated for close to 18 hours and while receiving intravenous epinephrine at 3 mcg/min, norepinephrine at 30 mcg/min, vasopressin a 0.03 units/min, phenylephrine at 150 mcg/min and dobutamine at 20 mcg/min. 

A formal 2-D echocardiogram was obtained which showed a global left ventricular dysfunction and hypokinesis with reduced ejection fraction of 35% and mildly reduced right ventricular dysfunction. No major valvular or pericardial pathology was noticed. Given the patient’s history and clinical features of hypothyroidism, a diagnosis of myxedema coma was made and treatment started with levothyroxine 125 mcg a day intravenously. Corticosteroids were discontinued due to concern of blockage of peripheral conversion of T4 to T3. T3 was unavailable in our city initially but was subsequently obtained and prescribed to our patient at 25 mcg of liothyronine three times a day. She responded very well to the treatment and was successfully weaned off all vasopressor support, liberated from mechanical ventilation on the fourth day and transferred out of the MICU on day five of admission. Limited repeat echocardiogram prior to transfer out of the MICU showed an ejection fraction of 65%.

Cultures, lumbar puncture and all imaging including brain MRI obtained during admission and MICU stay remained negative. A potential precipitating factor was not found and all empiric treatments were gradually withdrawn prior to the transfer out of MICU.

Retrospective history taking revealed patients’ non-compliance with levothyroxine treatment for the past 2 years. She had been given a dose of levothyroxine while she was admitted at the outside hospital the week previously leading to her relatively normal T4 level, suggesting inhibited peripheral conversion to T3 and thus the limited effect of intravenous levothyroxine initially. Surprisingly, despite the ordeal, she continued to refuse to take the medication once extubated and transferred to Medicine.

Discussion

A myxedema crisis is an extreme and life-threatening form of hypothyroidism that requires prompt diagnosis and treatment. Mortality rate has been reported as high as 60% despite appropriate diagnosis and management (1,2). Infections and discontinuation of thyroid supplements are the major precipitating factors. Other precipitants include hypothermia, gastrointestinal bleeding, congestive heart failure, cerebrovascular accident, metabolic disturbance and sedative drugs (3).

Myxedema crises manifests by involving multiple organ systems. Hypothermia can be profound and is usually the first sign of myxedema coma. Neuropsychiatric manifestations include confusion, lethargy, coma, psychosis (myxedema madness), and seizures. Respiratory depression is common likely due to depressed hypoxic and hypercapnic respiratory drive. Edema (myxedema) involving upper airways contributes to acute respiratory failure. Reduced intestinal motility leads to constipation, paralytic ileus and mega colon. Urine retention from bladder atony can be seen. Reduced glomerular filtration and reduced water excretion leads to hyponatremia, a consistent finding in myxedema crises.

Cardiovascular effects of myxedema crises include conduction abnormalities, reduced contractility, cardiomegaly and pericardial effusion. Sinus bradycardia, low voltage complexes, bundle branch blocks, complete heart blocks, and nonspecific ST-T changes in electrocardiogram have been reported. Prolonged QT interval and polymorphic ventricular tachycardia has been described as well (4). Depressed cardiac contractility leads to low stroke volume and cardiac output. Animal studies have documented that hypothyroidism leads to cardiomegaly from cardiac atrophy, impaired myocardial blood flow and loss of arterioles resulting in severe systolic dysfunction (5).

These cardiogenic effects of hypothyroid state leading to depressed ionotropy and chronotropy with compensatory vasoconstriction are believed to be a result of low intracellular T3. The hypothyroid heart attempts to perform by better coupling of ATP to contractile events until a precipitating event disrupts this fine balance (6). This resultant de-compensation leads to hypotension and cardiogenic shock that may not respond to vasopressors alone until thyroid hormone replacement is given.

Treatment usually involves intensive care admission with cardiopulmonary support, aggressive fluid and electrolyte management, treatment of underlying and precipitating factors and thyroid hormone replacement. Intravenous T4 is the most commonly used preparation as intestinal absorption may not be reliable. In severe illness, the conversion of T4 to T3 by 5’-monodeiodinase is impaired. Intravenous T3 preparation should be used. Improved cardiac function is reported in 24 hours when T3 replacement is used and it may take up to a week to notice beneficial effects with T4 replacement alone (7).

References

1. Mathew V, Misgar RA, Ghosh S, Mukhopadhyay P, Roychowdhury P, Pandit K, Mukhopadhyay S, Chowdhury S. Myxedema Coma: a new look into an old crisis. J Thyroid Res. 2011:493462.[CrossRef] [PubMed]
2. Wartofsky L, Myxedema Coma, Endocrinol Metab Clin N Am. 2006; 35(4): 687-98. [CrossRef][PubMed]
3. Brent GA, Davies TF. Hypothyroidism and thyroiditis. In: Melmed S, Polonsky KS, Reed P, Kronenberg HM, eds. Williams Textbook of Endocrinology. Philadelphia, PA: WB Saunders, 2008.
4. Schenck JB, Rizvi AA, Lin T. Severe primary hypothyroidism manifesting with torsades de pointes. Am J Med Sci. 2006 Mar; 331(3): 154-6. [CrossRef] [PubMed] 
5. Tang YD, Kuzman JA, Said S, Anderson BE, Wang X, Gerdes AM. Low thyroid function leads to cardiac atrophy with chamber dilatation, impaired myocardial blood flow, loss of arterioles, and severe systolic dysfunction. Circulation. 2005;112(20):3122-30. [CrossRef] [PubMed]
6. W. M. Wiersinga. Hypothyroidism and myxedema coma. In: Jameson JL, Legroot LJ, eds. Endocrinology: Adult and Pediatric. Philadelphia, PA: Saunders Elseiever, 6th edition, 2010:1607-22.
7. MacKerrow SD, Osborn LA, Levy H, Eaton RP, Economou P. Myxedema associated cardiogenic shock treated with intravenous triiodothyronine. Ann Int Med. 1992;117:1014-5. [CrossRef][PubMed] 

Reference as: Natt B, Siddiqi TA, Mosier J, Raz Y. Refractory cardiogenic shock. Southwest J Pulm Crit Care. 2013;7(4):246-50. doi: http://dx.doi.org/10.13175/swjpcc098-13 PDF