Approach to Bradycardia

Approach to Bradycardia

Last week we discussed an approach to bradycardia at morning report.

When there is an abnormality in a vital sign, the first step is to ensure stability.  

1.       Assess the ABCs, get monitors on, IV access

a.       Bradycardia is defined as a heart rate less than 60 beats per minute

2.       Ask yourself, is this unstable bradycardia?

a.       If yes à go down the unstable bradycardia ACLS algorithm

b.      If no à there is time to perform a focused history, physical and get investigations

3.       How do you define unstable bradycardia?

a.       Bradycardia that is causing one of the following symptoms:

                                                               i.      Hypotension

                                                             ii.      Acute altered mental status

                                                            iii.      Signs of shock

                                                           iv.      Ischemic chest discomfort

                                                             v.      Acute heart failure

4.       If there is unstable bradycardia, follow the ACLS algorithm including considering:

a.       Atropine

b.      Transcutaneous pacing

c.       Dopamine or epinephrine infusions

5.       If it is stable bradycardia, there is time to collect more information with a focused history, physical and get investigations

6.       An ECG is a key investigation!

7.       Two main question are:

a.       What type of rhythm is it?

b.      What is causing the bradycardia?

Rhythms associated with bradycardia

Bradycardia is an umbrella term that means that the heart rate is less than 60 beats per minute. But there can be several different rhythms that can cause a heart rate of less than 60 bpm.

-          Bradycardias can be classified narrow complex or wide complex (and as regular or irregular)

Narrow complex bradycardias

-          Sinus bradycardia

-          Junctional bradycardia

-          Sinus-node dysfunction

-          Second degree AV block, type I or II

-          Complete AV block (third degree AV block) with junctional escape

-          Atrial flutter or atrial fibrillation with high degree block/slow ventricular response

Wide complex bradycardia

-          Idioventricular rhythm

-          Complete AV block (third degree AV block) with ventricular escape

-          Any other causes of narrow complex bradycardia with aberrancy or bundle branch block

Causes of bradycardia

There are many causes of bradycardia. While not a fully inclusive list, causes can include:

Cardiac disease

-          Myocardial ischemia/MI

-          Myocarditis

-          Cardiomyopathies

-          Congenital disorders (such as muscular dystrophy)

Metabolic

-          Electrolyte disturbances (i.e. hypo- or hyper-kalemia)

-          Hypothyroidism

-          Hypothermia

Drugs

-          Medications (i.e. digoxin, beta blockers, calcium channel blockers, etc)

-          Toxidromes (cholinergic)

Iatrogenic

-          Post-cardiac procedure, surgery or transplantation  

Infectious

-          Endocarditis

-          Lyme disease

-          Typhoid fever

-          Chagas Disease

Autoimmune

-          Systemic lupus erythematosus

-          Rheumatoid arthritis

-          Scleroderma

Infiltrative

-          Sarcoidosis

-          Amyloidosis

-          Hemochromatosis

Physiological causes

-          Athletes

-          Vagal stimuli

Other causes

-          Hypoxia

-          Obstructive Sleep Apnea

-          Increased intracranial pressure (i.e. Cushing response)

References:

1.       Mangrum JM, DiMarco JP. The evaluation and management of bradycardia. N Engl J Med. 2000;342(10):703-9.

2.       Life in the Fastlane. Bradycardia. https://lifeinthefastlane.com/resources/bradycardia-ddx/

Alcohol withdrawal

Yesterday we discussed alcohol withdrawal.

Alcohol use can have effects on the body from head to toe. Complications of alcohol use can include:

-          Thiamine deficiency

o   Causing Wernicke encephalopathy characterized by the triad of encephalopathy, oculomotor dysfunction, and ataxia, or Korsakoff syndrome, the chronic consequence of Wernicke encephalopathy

-          Malnutrition and refeeding syndrome

-          Alcoholic ketoacidosis

-          Hypertension and cardiovascular disease

-          Cardiomyopathy

-          Liver disease including cirrhosis and hepatitis

-          Pancreatitis

-          Gastritis and esophagitis

-          Peripheral neuropathy

-          Bone marrow suppression

-          Injury/trauma

-          Malignancies, including GI, liver, and breast cancer

-          Psychiatric disorders

Another complication of alcohol use is alcohol withdrawal. There are several different phases of alcohol withdrawal. As such, the timing of symptoms compared to the last drink is helpful piece of information on history.

Manifestations of alcohol withdrawal:

-          Early alcohol withdrawal (onset 1-48 hours after last drink) can include symptoms such as insomnia, tremulousness, anxiety, GI upset, anorexia, headache, diaphoresis and palpitations.

-          Alcohol withdrawal seizures (onset 6-48 hours after last drink) are usually generalized, tonic-clonic seizures. Don’t forget basic principles such as accuchecks to ensure it is not a hypoglycemic seizures and reporting to the Ministry of Transportation for seizures. First line treatment of alcohol withdrawal seizures is benzodiazepines

-          Alcoholic hallucinosis (onset 12-48 hours after last drink) usually involves visual, auditory or tactile hallucinations. Importantly, orientation and vital signs are normal and that is what distinguishes alcoholic hallucinosis from delirium tremens.

-          Delirium tremens (onset 24-96 hours after last drink) is a serious manifestation of alcohol withdrawal characterized by delirium, agitation, tachycardia, hypertension, fever and diaphoresis. It is a medical emergency.

Principles of the management of alcohol withdrawal include:

1.       Rule out other causes of symptoms. Depending on the clinical presentation, for example confusion or change in level of consciousness, don’t forget to investigate for other causes of the presentation such as infection, co-ingestions, metabolic derangement, liver failure, GI bleeds, pancreatitis, and injuries (such as subdural hematoma) to name a few.

2.       Supportive care.

a.       Initial resuscitation including ABCs. Treat volume depletion.

b.      Treat any identified triggers or other causes of symptoms. There can be something else going on, such as pancreatitis or an infection, that led to reduced alcohol intake and then alcohol withdrawal.

c.       GIVE THIAMINE (before giving glucose) and a multivitamin  

d.      Nutritional support (may need to be NPO depending on level of consciousness to prevent aspiration) à consider other methods of nutritional support, get SLP and dietitian involved, and don’t forget to monitor for refeeding syndrome.

e.      Monitor severity of alcohol withdrawal with CIWA-Ar and clinical assessments.

                                                               i.      Items on the CIWA-Ar (Clinical Institute Withdrawal Assessment Scale for Alcohol, revised) include: nausea and vomiting, tremor, paroxysmal sweats, anxiety, agitation, tactile auditory and visual disturbances, headache, and orientation.  

f.        Treat alcohol withdrawal with benzodiazepines.

                                                               i.      Often diazepam or lorazepam are the benzodiazepines of choice and they are used in a symptom-triggered approach (administration and dose triggered by CIWA-Ar score)

                                                             ii.      Diazepam has a longer half-life so is usually the first choice to avoid recurrent withdrawal or seizures.

                                                            iii.      However, with cirrhosis or acute hepatitis, a benzodiazepine with a shorter halt-life such as lorazepam, may be preferred to avoid over-sedation.

                                                           iv.      Take a look and become familiar with the CIWA-Ar protocols at your institution.

                                                             v.      For refractory delirium tremens, barbiturates such as phenobarbital and/or propofol may be necessary.

References:

1.       Up-to-date “Management of moderate and severe alcohol withdrawal syndromes”. Hoffman et al. Last updated Jan 17, 2017.

2.       Schuckit M. Recognition and Management of Withdrawal Delirium. NEJM. 2014;371:2109-13. 

Clostridium difficile Infection

During morning report we discussed a case of Clostridium difficile Infection (CDI). Here are some key points about the risk factors, diagnosis, risk stratification, and management of CDI.

Pathophysiology and Risk factors:

-          Clostridium difficile is an anaerobic Gram-positive spore-forming bacillus

-          Transmitted through the fecal-oral route by spores that are resistant to heat, acid, and antibiotics

-          Colonizes the large intestine and makes exotoxins that cause colitis in susceptible patients

-          In a healthy host, colonization is prevented by barrier properties of a health fecal microbiota

-          Most of the risk factors for CDI have to do with a weakened fecal microbiota

-          Risk factors:

o   Antibiotics (Most important risk factor!)

§  Almost all antibiotics are a risk factor but classically think of fluoroquinolones, cephalosporins, clindamycin, ampicillin and amoxicillin (1)

§  Interestingly, a recent cohort study in JAMA Internal Medicine, showed that even the receipt of antibiotics by prior hospital bed occupants can increase the risk for CDI in subsequent patients who occupy the same bed! (2)

o   Advanced age

o   Chemotherapy

o   Underlying diseases (such as inflammatory bowel disease, immunosuppression) (1)

Diagnosis:

-          The diagnosis of CDI is usually made by C diff toxin assays in stool (either an enzyme immunoassay for toxins or a PCR test for microbial toxin genes)

-          Culturing Clostridium difficile in stool is not widely available and is not often used

-          Note that the C diff toxin assays may stay positive after a CDI is appropriately treated so a positive C diff stool test after an appropriate course of treatment for CDI needs to be interpreted with caution (i.e. involve the expertise of Infectious Disease)

Risk stratification and management:

-          How one treats CDI varies depending on the severity of the infection.

-          One resource I find very helpful is the Antimicrobial Stewardship Program of UHN/SHS best practices:

http://www.antimicrobialstewardship.com/antimicrobial-stewardship-best-practices (3)

-          This is their summary slide on C difficile severity Criteria:

Source: http://www.antimicrobialstewardship.com/antimicrobial-stewardship-best-practices (3)

-          And here is a summary of the treatment of CDI based on severity:

-           

Source: http://www.antimicrobialstewardship.com/antimicrobial-stewardship-best-practices (3)

-          Bottom line is that metronidazole is first-line for mild-moderate disease and ORAL vancomycin is first line for severe disease. Once there is complicated/fulminant disease, ORAL vancomycin and IV metronidazole are both given and General Surgery and Infectious Diseases consultations are key.

-          Keep in mind that the vancomycin needs to be given ORALLY! It is not absorbed in the GI tract and therefore will act in the colon where the infection is; IV vancomycin isn’t going to help.

-          There are subtleties to the treatment of recurrent CDI including much interest in fecal microbial transplantation, which has evidence supporting its effectiveness and cost-effectiveness in the treatment of recurrent CDI, including RCTs (4).

References:

1.       NEJM review article: Leffler D, Lamont JT. Clostridium difficile infection.  N Engl J Med. 2015;372(16):1539. http://www.nejm.org/doi/pdf/10.1056/NEJMra1403772

2.       Freedberg et al. Receipt of antibiotics in hospitalized patients and risk for Clostridium difficile infection in subsequent patients who occupy the same bed. JAMA Intern Med. 2016;176(12):1801-1808.

3.       Antimicrobial Stewardship Program of UHN/SHS best practices: http://www.antimicrobialstewardship.com/antimicrobial-stewardship-best-practices

4.       Health Quality Ontario. Fecal Microbiota therapy for Clostridium difficile infection: A health technology assessment. Ont Health Technol Assess Ser. 2016; 16(17):1-69. 

Approach to Adrenal Insufficiency

We recently discussed a case of adrenal insufficiency. Here is an overview and some key points about the presentation and work-up for adrenal insufficiency (AI):

Signs and symptoms:  * they are non-specific

History: Nausea, vomiting, anorexia, abdominal pain, presyncope, salt craving (only in primary AI)

Physical Exam: Evidence of volume depletion including tachycardia and hypotension, hyperpigmentation (only in primary AI)

Labs: Normocytic anemia, hyponatremia, hyperkalemia (only in primary AI), hypercalcemia, hypoglycemia

How to diagnose AI:

·         In patients who are unstable, with suspected severe adrenal insufficiency symptoms or adrenal crisis, the JCEM guidelines recommend immediate therapy with IV hydrocortisone at an appropriate stress dose prior to the availability of the results of diagnostic tests

o   There is some practice variation and no universally accepted or evidence-based “stress dose of steroids”

o   Some reasonable doses can include hydrocortisone 100mg IV x1 then hydrocortisone for a total of approximately 200mg IV/day (for example hydrocortisone 50mg IV q6h or hydrocortisone 100 mg IV q8h) x 24 hours then reduce the doses based on clinical picture)

o   If there is a need to give a stress dose of steroids immediately due to clinical instability but there is a plan to still test for AI after by measuring serum cortisol, giving dexamethasone may be a good choice of steroid, as it is not measured in the assays for serum cortisol (hydrocortisone will interfere with the test and is measured in the cortisol radioimmunoassay).  

·         Based on the most recent JCEM guidelines, the recommended test to diagnose adrenal insufficiency is a corticotropin stimulation test (ACTH stim test).

·         If a corticotropin stimulation test cannot be performed, measure morning (8am) serum cortisol

o   If 8 am cortisol <140 140="" nbsp="" nmol="" span="">à adrenal insufficiency

o   If 8 am cortisol 140-500 nmol/L à indeterminate à need further testing (ACTH stim test)

o   If 8 am cortisol >500 nmol/L à essentially rules out AI à in most cases no further testing necessary

Corticotropin stimulation test (ACTH stim test):

How to do it: There are 2 protocols of ACTH Stimulation tests. Both use synthetic ACTH (cosyntropin) to assess the adrenal’s response to ACTH.

Standard high-dose ACTH stimulation test: Give cosyntropin 250 mcg IV and measure serum cortisol at time 0, 30, 60 mins post-injection.

Low-dose ACTH stimulation test: Give cosyntropin 1 mcg IV and measure serum cortisol at time 0 and 30 mins post-injection.

Notes:

* Can also measure ACTH before giving the cosyntropin to help determine if it is primary or secondary AI

* Do the stimulation test in the morning as cortisol responses are greatest in the morning. If you do it in the evening, you could get a False Positive test in a normal individual.

* Theoretically the low-dose ACTH stim test is a more sensitive test, especially for secondary AI, as it is a more physiological dose of ACTH, but typically high-dose ACTH stim test in the standard test that is done first (it is what is recommended in JCEM guidelines)

*Hold oral contraceptives before ACTH Stim tests, as the increased cortisol-binding globulins with oral contraceptive can affect the results of the test (can lead to underestimation of hypocorticolism)

* If you suspect an adrenal crisis, do not delay glucocorticoid replacement therapy while awaiting the results of ACTH stim test to confirm the diagnosis. You can consider using dexamethasone as the initial steroid of choice as it does not interfere with serum cortisol assays.

How to interpret ACTH Stim test:

Peak serum cortisol >500 nmol/L at any point during ACTH stim test (before or after cosyntropin injection at 30 or 60 mins) à no AI à no further testing necessary

Peak serum cortisol <500 500="" acth="" during="" nbsp="" span="" stim="" test="">à indicates adrenal insufficiency à further testing to determine etiology

Determine etiology:

ACTH Stim test confirms adrenal insufficiency (cortisol remains <500 span="">à measure serum ACTH

ACTH >2-fold the upper limit of the reference range à consistent with Primary AI (including Addison’s disease) à further work up which may include CT adrenal, adrenal antibodies, 17-OH proesterone

ACTH in low/low-normal range à Secondary or tertiary AI à Pituitary MRI, measure other pituitary hormones to rule out panhypopituitarism

Management

Acute management (adrenal crisis): 

ABCs, IV normal saline, electrolyte management, stress-dose steroids (no universally accepted or evidence-based dose, one example is hydrocortisone 100mg IV x1 then hydrocortisone for a total of approximately 200mg IV/day (for example hydrocortisone 50mg IV q6h or hydrocortisone 100 mg IV q8h) x 24 hours then reduce the doses based on clinical picture)

Chronic management:

·         Glucocorticoid replacement: guidelines suggest hydrocortisone (15-25mg) or cortisone acetate (20-35mg) daily in two or three divided oral doses/day, with the highest dose given in the morning

·         Mineralocorticoid replacement: Fludrocortisone (starting dose 50-100 mcg) and no salt intake restriction. Monitor mineralocorticoid replacement based on clinical assessment (salt craving, postural hypotension, electrolytes).

·         Other: medical alert identification, patient education, patient education regarding stress dosing when sick (basics: double or triple dose of oral steroid when sick until recovery (usually 2-3 days); if not tolerating PO intake, need to come to hospital for IV steroids), education and consultation regarding peri-operative management.

References:

1.       Bornstein S et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guildeline. J Clin Endocrinol Metab. 2016;101(2):364-89

2.     Klose M et al. Factors influencing the adrenocorticotropin test: role of contemporary cortisol assays, body composition, and oral contraceptive agents.  J Clin Endocrinol Metab. 2007;92(4):1326. 

Group A Steptococcal infection

In morning report, we discussed the case of a man with HIV presenting with sepsis and odynophagia with head and neck lymphadenopathy and symptoms of sinusitis.

We discussed the following learning points:

1.       Head and neck infection: a history of odynophagia, lymphadenopathy and sinusitis is concerning for a head and neck infection. The differential diagnosis would include:

a.       Deep neck space infections such as retropharyngeal abscesses

b.      Peritonsillar abscesses and submandibular space infections (Ludwig’s angina)

c.       Suppurative parotitis

d.      Pharyngitis

e.      Lymphadenitis (including TB lymphadenitis)

f.        Epiglottitis  

g.       Laryngotracheitis

h.      Diphtheria

2.       CD4 count : we discussed that the differential diagnosis will change and be informed by the opportunistic infections that patients with HIV are susceptible to with different CD4 counts:

3.       Meningitis examination: With the history of fever and headache, the question of meningitis comes up. Looking at the JAMA Rational Clinical Examination article on “Does this adult patient have acute meningitis?” from 1999, absence of fever, neck stiffness and altered mental status effectively rules out meningitis. One of the most sensitive maneuvers in the diagnosis of meningitis is jolt accentuation (sensitivity 100%, specificity 54%, positive LR 2.2, negative LR 0); a negative jolt accentuation may essentially exclude meningitis.

In this case, there was no evidence of meningitis on exam (negative jolt accentuation) and swabs and blood cultures were positive for Group A Streptococcus (Sterptococcus pyogenes).  

4.       Group A Streptococcus (GAS) infections:

Types of GAS infection include:

-          Streptococcal tonsillopharyngitis “strep throat”

-          Skin and soft tissue infections

o   Cellulitis

o   Erysipelas

-          Necrotizing fasciitis

-          Myositits

-          Pneumonia

-          Postpartum endometritis

-          Bacteremia associated with toxic shock syndrome

Nonsuppurative Complications of GAS pharyngitis include:

-          Scarlet Fever

-          Rheumatic Fever

-          Glomerulonephritis

-          Toxic Shock Syndrome

Treatment of GAS:

-          GAS is universally sensitive to penicillin and as such penicillin is the first line treatment.

-          Clindamycin is generally used in addition to a beta-lactam in the treatment of invasive GAS has it inhibits protein synthesis, suppressing synthesis of bacterial toxins, and there is evidence that it reduces mortality.

-          For toxic shock syndrome, there is some evidence supporting the adjunctive use of IVIG

-          Don’t forget that early aggressive surgical intervention is key for invasive soft tissue infections, such as necrotizing fasciitis. 

References:

Attia et al. Does this adult patient have acute meningitis? JAMA. 1999;282(2):175-81.

Carapetis et al. Effectiveness of clindamycin and intravenous immunoglobulin, and risk of disease in contacts, in invasive group A streptococcal infections. Clin Infect Dis. 2014;59(3):358.   

Davies et al. Invasive Group A Streptococcal Infections in Ontario, Canada. NEJM. 1996;335:547-54.

Wessels. Streptococcal Pharyngitis. NEJM. 2011;364:648-55.