Mucormycosis is the generic name of an invasive fungal infection. It is caused by a variety of fungi, but the most common are from either the genus Rhizopus or Mucor, which is where the disease gets its name. Theses are ubiquitous fungi and do not cause disease in immunocompetent individuals. Rather, it is seen in those with primary or secondary immunosuppression. (1-3)

The most important risk factors, and therefore the populations affected, are diabetics and those with hematologic malignancy. Diabetes, specifically with ketoacidosis, is the main risk factor. (1,2) Neutrophil dysfunction, along with hyperglycemia and an iron rich environment induced by ketoacidosis allows for the fungi to avoid the immune system and thrive in a substrate rich environment. (3) Retrospective studies have reported over 80% of cases in those with diabetes, and 40% of those who previously did not have known history of the disease. (1) Hematologic malignancy, especially those with acute myelogenous leukemia are also at increased risk. Other immunosuppressive states and burn victims without a protective skin barrier are also at risk.

The three most common forms of disease are rhinocerebral, pulmonary and cutaneous. The most common is rhinocerebral. This is the classic disease state seen in patients with DM or DKA. Inhalation of spores leads to invasion of the sinuses. This leads to typical symptoms of sinusitis. However the hallmark feature is a necrotic eschar on the palate, nasal turbinates or external skin. Seeing this feature does not rule out mucormycosis, but absolutely rules it in. If cerebral or orbital invasion occurs, cranial nerve or ophthalmologic symptoms can develop. If these are seen in combination, it should be considered mucormycosis unless proven otherwise. (1,2)

The pulmonary form of the disease is rapidly progressive and has a high mortality rate (76%). (1) Manifestations would be similar to other forms of pneumonia, specifically invasive pulmonary aspergillosis. It would be difficulty to sore this out in the emergency department, but could be considered in the right patient population or in those who are failing to improve while on broad-spectrum antibiotics. (1,2)

The cutaneous form of mucormycosis can have variable presentations, but again if nerotic eschars are present, this needs to be in the differential. If invasion of the underlying soft tissues, muscle and bone occur, it can cause significant pain or present similar to necrotizing fasciitis. (1)

Source control is an important component of treatment. Consultation with subspecialties such as otolaryngology, ophthalmology or pulmonology should occur promptly. If history and physical exam are suggestive this should occur prior to further studies because this is a highly fatal disease that is a time sensitive emergency, often requiring extensive debridement. CT scans of affected areas can help in the diagnosis but do not show specific findings. Anti fungal therapy with the lipid formulation of amphotericin B at 5 mg/kg/day is the agent of choice. (2)

This is a rare disease that may never be encountered in the career of the emergency physician. It nevertheless should remain in the differential because of its high mortality rate that approaches 80% in invasive disease. While other forms of the disease may be hard to distinguish, the rhinocerebral form has hallmark physical exam findings that can aid in the diagnosis. For a terrific review of a case of mucormycosis, please use this link to the EM:RAP Podcast.



References

1. Petrikkos G, Skiada A, Lortholary O, Roilides E, Walsh TJ, Kontoyiannis DP. Epidemiology and clinical manifestations of mucormycosis. Clin Infect Dis. 2012 Feb;54 Suppl 1:S23-34
   
2. Long B, Koyfman A. Mucormycosis: what do emergency physicians need to know? Am J Emerg Med. 2015 Aug 28
   
3. Ibrahim AS, Spellberg B, Walsh TJ, Kontoyiannis DP. Pathogenesis of mucormycosis. Clin Infect Dis. 2012 Feb: 54 Suppl1:S16-22
   

Submitted by Dr. Michael Craddick, PGY-2

Sticking with the pediatric theme, this post is going to give an overview on the management of pediatric sepsis. We all feel relatively comfortable managing the adult patient with sepsis. Sure, some items will be case specific, but the management is well taught and a hot topic right now. Pediatrics, on the other hand, is not as mainstream. Just as with everything else, kids are not just small adults. As such I hope to provide some important differences in the management of this sick population.

Definitions and Epidemiology (1-3)
Approximately 100,000 pediatric patients are diagnosed with severe sepsis per year in the United States. That number drops to 75,000 for septic shock. 

The definitions of pediatrics, like everything else, are age based. While the values pertinent to each age are noted, remembering 140 (HR) and 40 (RR) gets you pretty close. Aside from that, the definitions of septic shock is important, because it does not just include hypotension. Rather, other signs of hypo perfusion can be used to make the diagnosis, and reliance on BP to drop can result in delayed recognition or management. The big pearl here is you do not need hypotension to be in shock.

SIRS - Dependent on Age, >/= 2 or more of the following

• Temperature < 36 C (96.8 F) or > 38.5 C (101.3 F)
  
• Tachycardia 

                Newborn - 1 year: HR > 180 bpm
                1 - 5 years; HR > 140 bpm
                5 - 12 years; HR > 130 bpm 
                12 - 18 years; HR > 110 bpm
                > 18 years; HR > 90 bpm

• Tachypnea 
  

                Newborn - 1 week: RR > 50
                1 week - 1 month; RR > 40
                1 month - 1 year; RR > 34
                1 - 5 years; RR 22
                5 - 12 years; RR 18
                12 - 18 years; RR 14

• WBC < 4,000 cells/mL3; > 12,000 cells/mL3; or > 10% bands
  

Sepsis
SIRS and suspect or present source of infection

Severe Sepsis
Sepsis with organ dysfunction, hypotension, and tissue hypoperfusion (altered mental status, acute renal failure, acute liver failure, decreased urine output, etc)

Septic Shock
Sepsis plus cardiovascular dysfunction despite 40 mL/kg fluid administration in one hour (not just defined by blood pressure)

• Hypotension
  

                0 - 28 days, < 60
                1 - 12 months, < 70
                1 - 10 years, < 70 + (age in years x 2)
                > 10 years, < 90

• Need for vasoactive medication to maintain blood pressure in normal range
  

                Two or more of the following
                Unexplained metabolic acidosis: base deficit > 5.0 mEq/L
                Increased arterial lactate > 2 times upper limit of normal
                Oliguria: urine output < 0.5 mL/kg/hr
                Prolonged capillary refill > 5 sec
                Core to peripheral temperature gap > 3C

Diagnosis (3,4)
Although the diagnosis of sepsis can eventually be straight forward, the initial assessment can be challenging. Histories can be limited in non-verbal children or if caregivers are not available. The most important clinical characteristics are tachycardia, fever, and mental status change, as well as respiratory rate and peripheral capillary refill. While all of these clinical findings are not unique to sepsis, they are nevertheless the most commonly used by most pediatric emergency physicians. Like an case of sepsis, your history, physical and workup can most often point toward a source.

Management (3, 5, 6)
The general approach of securing the airway, if needed, and administering early fluids and antibiotics applies to both adults and pediatric sepsis. Here are some specific differences though when if comes to kids.

Airway

• Give supplemental oxygen to all patients in septic shock
  
• Intubation and mechanical ventilation indicated if cannot reach oxygen saturation of 92% despite supplementation, or if pO2 < 65 mmHg
  
• No atropine pretreatment (dropped in new 2015 ACLS guidelines)
  
• Avoid etomidate (controversial)
  
• Ketamine or versed/fentanyl for RSI
  

Fluid Management

• 20 mL/kg and reassess
  
• Repeat 2-3 times if no evidence of rales, respiratory distress or hepatomegaly develop
  
• Crystalloid or colloid can be used (NS most common)
  
• Administer through 3-way stop cock or "push-pull" method (using a 60 mL syringe, draw fluid out of the bag and then either turn the stop cock or inject directly into the line as many times as needed to give desired quantity of fluid)
  

                Desired rate of infusion is at least 60 mL/kg in < 60 minutes
                Each bolus is to be given in 5-10 minutes to allow for reassessment

• Hypoglycemia may also occur and should be corrected (remember rule of 50's; dose of fluid and concentration of dextrose equal 50)
  

                Infants: 5-10 mL/kg D10W
                Children: 2-4 mL/kg D25W

Vasoactive Agents

• Dopamine 1st line
  

                Initial dose: 5-10 mcg/kg/min, max 20 mcg/kg/min

• "Warm Shock" (shock with vasodilation or flash cap refill)
  

                Norepinephrine 0.05-1 mcg/kg/min

• "Cold Shock" (shock with vasoconstriction)
  

                Epinephrine 0.05-1 mcg/kg/min

Antibiotics
Remember 15 for vancomycin, 50 for everything else, and look up acyclovir

• Neonates: ampicillin 50 mg/kg, cefotaxime 50 mg/kg, +/- acyclovir
  
• > 4 weeks: vancomycin 15 mg/kg and ceftriaxone 50 mg/kg
  

I know it is a quick and brief review, but hope it helps the next time you approach one of these patients. Until next time.


References

1. Goldstein B, Giroir B, Randolph A. International Consensus Conference on Pediatric S. International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatr Crit Care Med. 2005 Jan;6(1):2-8.
   
2. Singhal S, Allen MW, McAnnally JR, Smith KS, Donnelly JP, Wang HE. National estimates of emergency department visits for pediatric severe sepsis in the United States. PeerJ. 2013;1:e79.
   
3. Silverman AM. Septic shock; recognizing and managing this life-threatening condition in pediatric patients. Pediatr Emerg Med Pract. 2015 Apr;12(4):1-25;quiz6-7.
   
4. Thompson GC, Macias CG.Recognition and management of sepsis in children: practice patterns in the Emergency department. J Emerg Med. 2015 Oct;49(4):391-9.
   
5. Association AH. Pediatric Advanced Life Support. 2015 [cited 2015 November 18]; available from https://eccguidelines.heart.org/index.php/circulation/cpr-ecc-guidelines-2/part-12-pediatric-advanced-life-support/
   
6. Associate AH. Pediatric Advanced Life Support. United States of America: First American Heart Association Printing; 2010.
   

Submitted by Dr. Michael Craddick, PGY-2

References
1 Mick NW. Pediatric Fever. In: Marx J, Hockenberger RS, Walls, RM, et al, editor. Rosen's Emergency Medicine: Concecpts and Clinical Practice. 8th ed. Philadelphia: Elseveir Saunders; 2014.

2 Nadkarni MD. Fever and Serious Bacterial Illness. In: Cline DM, Ma OJ, Cydulka RK, Thomas SH, Handel DA, Meckler GD, editors. Tintinalli's Emergency Medicine: Just The Facts. 3rd ed. China: McGraw-Hill; 2013.

3 Morley EJ, Lapoint JM, Roy LW, et al. Rates of positive blood, urine, and cerebrospinal fluid cultures in children younger than 60 days during the vaccination era. Pediatr Emerg Care. 2012 Feb;28(2):125-30.

4 American College of Emergency Physicians Clinical Policies C, American College of Emergency Physicians Clinical Policies Subcommittee on Pediatric F. Clinical policy for children younger than three years presenting to the emergency department with fever. Ann Emerg Med. 2003 Oct;42(4):530-45.

5 Martinez E, Mintegi S, Vilar B, et al. Prevalence and predictors of bacterial meningitis in young infants with fever without a source. Pediatr Infect Dis J. 2015 May;34(5):494-8.

6 Sloas A. PEM ED Podcast.  Fever of Unknown Source - Part 1; 2011.

7 Sloas A. PEM ED Podcast.  Fever of Unknown Source - Part 2; 2011.

8 Baker MD, Bell LM, Avner JR. Outpatient management without antibiotics of fever in selected infants. N Engl J Med. 1993 Nov 11;329(20):1437-41.

9 Jaskiewicz JA, McCarthy CA, Richardson AC, et al. Febrile infants at low risk for serious bacterial infection--an appraisal of the Rochester criteria and implications for management. Febrile Infant Collaborative Study Group. Pediatrics. 1994 Sep;94(3):390-6.

10 Dagan R, Powell KR, Hall CB, Menegus MA. Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis. J Pediatr. 1985 Dec;107(6):855-60.

11 Baskin MN, O'Rourke EJ, Fleisher GR. Outpatient treatment of febrile infants 28 to 89 days of age with intramuscular administration of ceftriaxone. J Pediatric. 1992 Jan;120(1):22-7.


Submitted by Dr. Michael Craddick, PGY-2

Postural modification to the standard Valsalva maneuver for emergency treatment of SVT (REVERT): a randomized controlled trial

This was a randomized controlled, parallel group trial at Emergency Departments in England. The study compared the well known standard Valsalva maneuver to attempt conversion of SVT to sinus rhythm, to a modified Valsalva maneuver. The primary outcome was return to sinus rhythm at 1 minute after the chosen intervention. The standard maneuver required participants in a semi-recumbent position to perform the standardized strain to a pressure of 40 mmHg sustained for 15 seconds by forced expiration, and remain in that position for 60 seconds. In the modified maneuver, participants performed the standardized strain in the same semi-recumbent position but immediately after were laid flat and had their legs raised to 45 degrees for 15 seconds. They were then returned to the semi-recumbent position for the remaining 45 seconds prior to re-assessment of their rhythm. At the conclusion of the study, the results were that 17% of the participants assigned to the standard Valsalva achieved sinus rhythm, compared to 43% of participants who achieved sinus rhythm with the modified Valsalva. A major benefit of the modified Valsalva is that it can be easily taught to patients and appears to be more effective than the standard. Another benefit of discovering a more efficacious maneuver for conversion to sinus rhythm is that the effects of adenosine can be extremely unpleasant to patients, and this may decrease that rate at which it is administered. This can be easily implemented in our ED.

Intercepting wrong-patient orders in a computerized provider order entry system

Even though there are many safety benefits of computerized provider order entry, there are still errors that can be made, such as ordering on the wrong patient. This study evaluated the short and long term effects of a computerized provider order entry based patient verification intervention to reduce wrong patient orders in 5 emergency departments. The goal of this study was to reduce wrong-patient orders. Prior to implementing the intervention, monthly measurements of wrong-patient ordering rates were obtained, and then compared to the rates after the implementation of the verification process. The intervention focused on providing some sore of visual cues about the patient to the provider, immediately prior to placing an order. A dialog box was displayed at the beginning of every ordering session, requiring providers to verify the patient for whom they were placing an order. The short term results were that wrong patient orders were reduced by 30% immediately after implementation of this dialog box intervention. The long term results showed that after 2 years, the rate of wrong patient orders remained 24.8% less than before intervention. One down-side of this type of intervention is the effect of alert fatigue on providers. However, the effect of alert fatigue on the response rate to alerts was analyzed and the slight decline in the effect of the patient verification module in the study was less severe and not statistically significant. Overall this was a though provoking study and in our discussion we agreed that spending an extra few seconds to verify a patient is worthwhile when compared to the potential risks of harming a patient with incorrect orders, and the time spend having to undo certain orders even if the mistake w

Fluid overload in patients with severe sepsis and septic shock treated with early goal directed therapy is associated with increased acute need for fluid related medical interventions and hospital death

This was a retrospective cohort study of adults admitted with severe sepsis and septic shock to the MICU of a tertiary care academic hospital. The goal of the study was to determine the potential morbidity and mortality associated with fluid overload in those receiving adequate EGDT for both sepsis and septic shock on days 1 and 3, regardless of vasopressor use. Early fluid resuscitation through EGDT has been shown to decrease in hospital mortality and improve morbidity by decreased occurrence of organ dysfunction. However, there are adverse effects of fluid overload such as pulmonary edema and increased cardiac, that are detrimental to the patient. The study found that the clinical evidence of fluid overload was common and associated with increased medical interventions such as thoracentesis and diuretics, and increased hospital mortality. Interestingly, the study found that patients with fluid overload did not have a statistical difference in fluid administration. Additionally, BMIs were significantly higher in the fluid overload group, leading the reader to believe that those patients were at a higher risk of fluids overload in the first place. There were several limitations to the study, such as clinical evidence of overload being subjective, quality of documentation, and the retrospective nature of the study, which led to some gaps in the data. A major limitation was that the study was non-randomized. Since the study was not randomized, it is possible that certain patient factors may have been responsible for the development of fluid overload rather than the resuscitation approach. Since it is impossible to tell if the method of resuscitation caused the fluid overload or the patient's risk factors, we agreed in our discussion that we should not alter the way we resuscitate our patients at this time, but that we should be meticulously reassessing our patients for improvement v. deterioration and adjusting our therapies accordingly.