A Note on Parkinsonism–Hyperpyrexia Syndrome (PHS)

Parkinsonism–hyperpyrexia syndrome (PHS) is potentially one preventable entity in hospitals including ICUs. It mostly occurs when patient's regular Parkinson's disease medications (levodopa, dopamine agonists, or amantadine) get interrupted for some reason including NPO status in the hospital, noncompliance or before/after surgery. Post-surgery, it may mimic neuroleptic malignant syndrome (NMS). It is characterized by hyperthermia, dysautonomia, mental status change, rigidity, and elevated CK levels. Other causes which may induce PHS are discontinuation of subthalamic nucleus deep brain stimulation (DBS), sepsis, hot weather, dehydration, and reduction of the previous dose of medication. Treatment is supportive and restart of medications. Few reports suggest that dantrolene may help in PHS alike NMS. 


 Reference: 

Robottom BJ, Weiner WJ, Factor SA. Movement disorders emergencies. Part 1: hypokinetic disorders. Arch Neurol 2011; 68:567–572.

Q: What constitutes the fifth generation Cephalosporin?

Answer: It covers Methicillin-Resistant Staphylococcus aureus (MRSA)

Medicine under its banner is Ceftaroline, which is active against MRSA, Gram-positive bacteria as well as maintaining broad-spectrum activity against Gram-negative bacteria.

Q: "String sign" can be seen in which of the following diseases?

A) Esophageal Achalasia
B) Ulcerative Colitis
C) Crohn Disease
D) Perforated duodenal ulcer
E) Necrotizing Pancreatitis


Answer: C

Crohn's Disease causes severe ulceration and consequently causes spasm of the terminal ileum. If contrast is given, terminal ileum appears like a string. Though it can be seen in other similar conditions but is considered to be the hallmark of Crohn disease.

Q: Why endomyocardial biopsy has high false negative results in cardiac sarcoidosis?


Answer: Endomyocardial biopsy in cardiac sarcoidosis has a very high rate of false negative results due to two reasons. First, the disease has a patchy distribution. And second, myocardial granulomas usually affects the basal and lateral left ventricular (LV) wall regions which are difficult to reach for biopsy.


Reference: 

Uemura A, Morimoto S, Hiramitsu S, et al. Histologic diagnostic rate of cardiac sarcoidosis: evaluation of endomyocardial biopsies. Am Heart J 1999; 138:299.

Q: What is the appropriate dose of oral vancomycin in C.diff. associated diarrhea  (CDAD)?


Answer:  125 mg four times daily

Though popular dose is 500 mg four times daily, but studies fail to show any superiority of higher dose.



References: 

1. Fekety R, Silva J, Kauffman C, et al. Treatment of antibiotic-associated Clostridium difficile colitis with oral vancomycin: comparison of two dosage regimens. Am J Med 1989; 86:15. 

2. Cohen SH, Gerding DN, Johnson S, et al. Clinical practice guidelines for Clostridium difficile infection in adults: 2010 update by the society for healthcare epidemiology of America (SHEA) and the infectious diseases society of America (IDSA). Infect Control Hosp Epidemiol 2010; 31:431.

Q: How Heparin and warfarin effect Anti-Thrombin (AT) activity?



Answer: Heparin, particularly unfractionated, can lower AT activity and may lead to undue replacement of AT even if not required. On the other hand, Warfarin may increase AT activity and may show normal AT level in patients with AT deficiency.

Q: At what level of hyperphosphatemia dialysis is usually indicated?



Answer:  If phosphate level more than 12 mg/dL

Dialysis may also be indicated at lower level of hyperphosphatemia, like between 8 to 10 mg/dL, if patient has  symptomatic hypocalcemia.

Q: Chest tube should be removed at end-inspiration or end-expiration? (select one)


Answer:  Does not matter!!

Though arguments have been made in favor of pulling chest tube both  at end-inspiration and end-expiration. In actuality, as far as patient is not actively breathing, there is no difference in post-pull pneumothorax by either method.


Reference:  

Bell RL, Ovadia P, Abdullah F, et al. Chest tube removal: end-inspiration or end-expiration? J Trauma 2001; 50:674.

Q: How Auto-PEEP can be suspected by physical exam?


Answer: Auto-PEEP can be detected by auscultation of the chest. During Auto-PEEP, inspiratory airflow will be heard before the expiratory airflow ceases. Actually, it can also be palpated with hands on the chest. Confirmation can be done by auscultation of the expiratory valve of the ventilator and listening for persistence of airflow at end-expiration.


Reference: 

Kress JP, O'Connor MF, Schmidt GA. Clinical examination reliably detects intrinsic positive end-expiratory pressure in critically ill, mechanically ventilated patients. Am J Respir Crit Care Med 1999; 159:290.

Q: About what percentage of circulating platelets are estimated to be held in reserve in the spleen? 

Answer:  About 25%

This explains thrombocytopenia with splenomegaly and thrombocytosis post splenectomy. Venous thrombosis may occur postsplenectomy with platelet counts more than 600 to 800 K/μL. Arterial thrombosis is less likely to occur resulting in CVA or acute MI etc.

Q: Patients with hemochromatosis are vulnerable to infection with which of the following organism

A) Vibrio Vulnificus
B) Clostridium Septicum
C) Clostridium Tertium
D) Staphylococcus Aureus 
E) Staphylococcus Epidermidis


Answer:  A

Growth of V. vulnificus is partly dependent on the availability of iron and directly related to the transferrin percentage saturation with iron. Once transferrin saturation goes above 70 percent, growth of the bacterium is nearly exponential.

But patients without hemochromatosis may develop severe V. vulnificus sepsis if expose to seawater (marine) with skin breakdown.




Reference:

Kim CM, Park RY, Choi MH, et al. Ferrophilic characteristics of Vibrio vulnificus and potential usefulness of iron chelation therapy. J Infect Dis 2007; 195:90.

Q: What is the basis of underlying patho-physiology of adrenal hemorrhage in ICU patients?

Answer: Arterial supply of adrenal gland is high but it relies on only one vein for drainage. During stress as occurs in many critical care patients, there is a rise in ACTH secretion, which stimulates the adrenal arterial blood flow but venous capacity may remain limited and may lead to adrenal hemorrhage. And, the situation may get worse if a patient is on anticoagulation. Superimposed factors in the stressful situation are adrenal vein spasm induced by pressors or high catecholamine levels or adrenal vein thrombosis induced by disseminated intravascular coagulation (DIC). 

Q: 19-year-old female is admitted to ICU with dehydration and multiple electrolyte disorder. The Patient was dropped at ER door by her roommate. Patient herself seems to be an unreliable historian. Hospital chart shows only one overnight previous hospitalization for dehydration secondary to vomiting. But chart shows referral for Maudsley family therapy. What is the probable diagnosis of patient's dehydration and electrolyte imbalance?


Answer: Bulimia

Maudsley family therapy is a family based approach first developed at the Maudsley Hospital, London for the treatment of anorexia in bulimia.  It is described as more of a pragmatic psycho-social approach. Treatment is divided into 3 main phases which are further subdivided into many sessions.

• Phase I: Weight restoration
• Phase II: Returning control over eating to the adolescent
• Phase III: Establishing healthy adolescent identity

Reference:

Lock J, le Grange D; Le Grange (2005). "Family-based treatment of eating disorders". The International Journal of Eating Disorders. 37: S64–7; discussion S87–9.

Q: If patient is on Intra-Aortic Balloon Pump (IABP), how frequent distal pulses should be checked?


Answer: 

All patients who have IABP insertion, should get distal pulses checked and documented three times per day.

Q: Donor lung for lung transplant is usually preserved at what temperature?


Answer:  4 to 8ºC

During donor lung procurement, lungs are flushed with preservation solution at a temperature of 4 to 8ºC and stored at 4 to 8ºC. Ischemic times of up to 8 hours is usually acceptable.

Q: A majority of ESRD (End Stage Renal Disease) patients are either on angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). How many days before elective surgery they should be preferably discontinued?


Answer:  48 hours

A majority of patients, with ESRD and on dialysis are either on ACE-inhibitors or ARBs. Ideally, it should be held at least 48 hours before surgery to avoid refractory vasodilation/vasoplegia.

Q; How you calculate pediatric dose for antivenom? 


Answer: Interestingly, there is no pediatric antivenom dose. It is same as in adults. Only difference is that, sometime it is difficult to quickly establish IV in children and so antivenom can be given via intraosseous route.

Q: Acute promyelocytic leukemia (APL) is a medical emergency because? 

A) Life-threatening hemorrhagic coagulopathy 
B) High risk of massive Pulmonary Embolism
C) Cardiogenic shock
D) Neutropenic fever, sepsis and death
E) Massive stroke


Answer: A

Acute promyelocytic leukemia (APL) is a medical emergency due to its characteristic coagulopathy, causing fatal hemorrhage. Though aggressive transfusions of platelets and cryoprecipitate may help but mainstay of treatment is initiation of treatment with all-trans retinoic acid (ATRA) ASAP even though definitive confirmation of the diagnosis is not  made.


Reference: 

1. Park JH, Qiao B, Panageas KS, et al. Early death rate in acute promyelocytic leukemia remains high despite all-trans retinoic acid. Blood 2011; 118:1248. 

Q: Once patient is put on Extracorporeal membrane oxygenation (ECMO) - select one

A) Ventilator support should be minimized
B) Ventilator support should be maximized
C) Ventilator support should be managed as per previous
D) Tidal volume should be maximized
E) Plateau pressure less than 35 cm H2O 



Answer:  A

Once patient is put on ECMO, goal should be "ultra-protective ventilation strategy" with

• Tidal volume less than 4 ml/kg of Predicted  Body Weight,
• Plateau pressure  less than 25 cm H2O
• Application of tolerable and optimum PEEP

Reference: 

Matthieu Schmidt, Vincent Pellegrino, Alain Combes, Carlos Scheinkestel, D Jamie Cooper and Carol Hodgson - Mechanical ventilation during extracorporeal membrane oxygenation - Critical Care 2014 18:203 - Published: 21 January 2014

Q: What could be one way of detecting the cause of Hepatocellular Carcinoma (HCC) radiologically?


Answer: 

If radiologically, HCC appears nodular, the probable cause is cirrhosis. And, if it shows infiltrative appearance, the probable cause of HCC is chronic hepatitis B.


Reference: 

Benvegnù L, Noventa F, Bernardinello E, et al. Evidence for an association between the aetiology of cirrhosis and pattern of hepatocellular carcinoma development. Gut 2001; 48:110.

Q: If patient with Aortic dissection complains of "tearing" posterior chest or back pain, what does it probably means?



Answer: 

C/O "tearing" posterior chest or back pain probably means that the dissection progresses distal to the left subclavian artery.

Q: Colestipol and Cholestyramine are used as adjunctive therapy for relapsing C. Diff.  colitis. Which one precaution should be taken in their administration? 


Answer:  Colestipol and cholestyramine are anion-binding resins which are not indicated for primary treatment for C. difficile colitis but are known for decades to be used as adjunct therapy for relapsing infection. But as they are anion-binding resins, they binds oral vancomycin; thus, the resin should be administrated at least 2 to 3 hours apart from the vancomycin.


References: 

1. Taylor NS, Bartlett JG. Binding of Clostridium difficile cytotoxin and vancomycin by anion-exchange resins. J Infect Dis 1980; 141:92

2. Kreutzer EW, Milligan FD. Treatment of antibiotic-associated pseudomembranous colitis with cholestyramine resin. Johns Hopkins Med J 1978; 143:67. 

Q: Which of the following are the treatment of refractory Thrombotic thrombocytopenic purpura(TTP)? 

A) Plasma Exchange 
B) Glucocorticoids
C) Rituximab 
D) All of the above


Answer: D

The objective of above question is to bring in attention the benefit and use of Rituximab in the treatment of TTP, particularly in refractory cases. Those patients who do not respond to daily Plasma Exchange along with the addition of glucocorticoids or who relapse right after the Plasma Exchange is stopped. Addition of Rituximab may do the trick.

Q: Which of the following is not yet established as a standard of treatment during the management of Tumor Lysis Syndrome (TLS)?

A) IV Hydration
B) Rasburicase
C) Allopurinol 
D) Febuxostat
E) Dialysis


Answer:  D

 Febuxostat is an excellent selective inhibitor of xanthine oxidase for the management of chronic hyperuricemia in gout. At this given point, data is insufficient to use it during the management of TLS. Another disadvantage is its potential hepatotoxicity.  Febuxostat should only be used where allopurinol or rasburicase cannot be used for any reason. All other choices are well established modalities in the treatment of TLS. Dialysis is required in about 5% of TLS patients. 


References / further reading:

1.Coiffier B, Altman A, Pui CH, et al. Guidelines for the management of pediatric and adult tumor lysis syndrome: an evidence-based review. J Clin Oncol 2008; 26:2767.

2. Spina M, Nagy Z, Ribera JM, et al. FLORENCE: a randomized, double-blind, phase III pivotal study of febuxostat versus allopurinol for the prevention of tumor lysis syndrome (TLS) in patients with hematologic malignancies at intermediate to high TLS risk. Ann Oncol 2015; 26:2155.

3. Howard SC, Jones DP, Pui CH. The tumor lysis syndrome. N Engl J Med 2011; 364:1844.

Q: How many types of Myocardial Infarction (MI) has been defined?


Answer:  Five

According to Joint Task Force of the European Society of Cardiology, American College of Cardiology Foundation, the American Heart Association, and the World Heart Federation, MI can be subtyped into five categories according to their cause

Type 1 - MI due to to a pathologic process in the wall of the coronary artery like plaque erosion, fissuring, or dissection.

Type 2 -  MI consequent to increased oxygen demand or decreased supply 

Type 3 -  Sudden unexpected cardiac death before biomarkers could be checked

Type 4a  - MI related to PCI

Type 4b  - MI related to stent thrombosis

Type 5 - MI related to CABG


Reference: 

1. Thygesen K, Alpert JS, White HD, Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007; 28:2525.

2. Thygesen K, Alpert JS, Jaffe AS, et al. Third universal definition of myocardial infarction. Circulation 2012; 126:2020.

Q: What is the major cause of meningitis in systemic lupus erythematosus(SLE) patients?


Answer:  Iatrogenic

Patients with SLE develops meningitis mostly due to medications, used for relief or treatment. It may be due to either direct cause from ibuprofen or azathioprine (aseptic meningitis) or may be due to medications causing immunosuppression, causing bacterial, cryptococcal or tuberculous meningitis.

Q: Potassium repletion is available in various preparations like potassium chloride, potassium phosphate, potassium citrate, potassium acetate or potassium gluconate. Why potassium chloride is a preferred method?


Answer:  Out of all potassium preparations, potassium chloride is preferred for two reasons. First, it raises the serum potassium concentration at a faster rate. This is due to the fact that chloride is primarily an extracellular anion and it does not enter cells, thereby it promotes maintenance of the administrated potassium in the extracellular fluid. Second, unlike potassium bicarbonate or when its precursor potassium acetate or potassium citrate are  administrated it does not cause metabolic alkalosis, which is itself a cause of hypokalemia. Potassium bicarbonate or its precursors are preferable when hypokalemia and metabolic acidosis exist together. 




Reference:

Villamil MF, Deland EC, Henney RP, Maloney JV Jr. Anion effects on cation movements during correction of potassium depletion. Am J Physiol 1975; 229:161.

Q: Which of the following statement is true regarding hemodialysis?

A) 
Urea, creatinine and potassium move from blood to dialysate
Calcium and bicarbonate move from dialysate to blood.

B) 
Urea, creatinine, and calcium  move from blood to dialysate
Potassium and bicarbonate move from dialysate to blood.

C) 
Bicarbonate, creatinine and potassium move from blood to dialysate
Calcium and Urea move from dialysate to blood.

D) 
Urea, creatinine, Calcium and potassium move from blood to dialysate
Bicarbonate move from dialysate to blood.



Answer: A

In hemodialysis solutes passively diffuses down its concentration gradient from one fluid compartment into the other. Urea, creatinine, and potassium move from blood to dialysate, and calcium and bicarbonate move from dialysate to blood. The net effect is a reduction in the blood urea nitrogen and plasma creatinine concentration and an elevation in the plasma calcium and bicarbonate concentrations.

Q: What could be "one good way" to minimize the complication on exchange of Endotracheal tube (ETT) ?  


Answer: 

At least one study shows that use of video laryngoscopy  decrease the number of attempts of ETT exchange on first try. It includes life threatening complications as severe hypoxemia, esophageal intubation, arrhythmia etc.


 Reference: 

 Mort TC, Braffett BH. Conventional Versus Video Laryngoscopy for Tracheal Tube Exchange: Glottic Visualization, Success Rates, Complications, and Rescue Alternatives in the High-Risk Difficult Airway Patient. Anesth Analg 2015; 121:440.

Q: What is the advantage of measuring tryptase in anaphylaxis over histamine?



Answer; 

Plasma histamine levels need to be measured in less than 30 minutes after anaphylaxis event, though metabolites of histamine accumulated in urine stay elevated for few hours and can be measured. Tryptase has advantage of longer time window, and can be measured from 15 minutes to 3 hours after onset of symptoms. There are two tests for tryptase

1) Total tryptase and 
2) Mature tryptase

Mature tryptase correlates more with the anaphylaxis but is not widely available. Total tryptase can be measured and followed serially.

Diagnosis of anaphylaxis is usually made on clinical grounds and above tests are more of academic interests, or if diagnosis is in question.



Reference
Schwartz LB. Diagnostic value of tryptase in anaphylaxis and mastocytosis. Immunol Allergy Clin North Am 2006; 26:451.