Q1.1

Question of the Week

Hypersensitivity to what two foods is a contraindication to using propofol?

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Case 3.2

critical-care2

Prepared by Dr Kyle Perry

Case presentation:

A 64 year-old male presents to the emergency department pulseless with CPR in process.  EMS reports that the patient had a witnessed arrest in a nearby casino and bystander CPR was promptly initiated.  EMS arrived approximately 10 minutes after the collapse and placed a combitube before transporting the patient to the hospital.  In the ED, the patient was intubated and placed on a monitor which showed pulseless electrical activity (PEA.)  The patient received multiple doses of epinephrine and atropine and was then found to be in ventricular fibrillation.  He was then defibrillated and converted to sinus rhythm with return of pulses.  Hypothermic therapy was initiated, and the patient was admitted to the ICU.  The patient gradually became hypotensive, and vasopressors were started and an aortic balloon pump was placed for pressure support.  Initially, his Troponin I was 0.07, but gradually increased to 1.11 after 2 hours, 6.03 after 7 hours, and 19.93 after 14 hours.  Initial ECG showed a left bundle branch block.  He underwent a cardiac catheterization on hospital day #2 which showed a total occlusion of the right coronary artery.  Stent placement was attempted by was unsuccessful.  The patient expired on hospital day #3.

Pulseless Electrical Activity:

The term PEA can be used to describe any organized or disorganized rhythm that is unable to produce a palpable pulse.  For example, a patient can show normal sinus rhythm on the monitor, but if no pulse is present, the patient is still said to be in PEA.  The American Heart Association has divided the PEA algorithm into to basic pathways:  “Shockable” rhythms and “Not Shockable” rhythms.  “Shockable” rhythms include ventricular fibrillation and ventricular tachycardia.  The key component to either pathway is high quality CPR.  The central medications to the algorithms are Epinephrine 1 mg q 3-5 minutes and Atropine 1 mg q 3-5 minutes (up to 3 doses.)  Treatable causes of PEA should be sought after and reversed.  These are often referred to as the H’s and T’s.

Hypovolemia

Hypoxia

Hydrogen ion (acidosis)

Hypo/hyperkalemia

Hypoglycemia

Hypothermia

___________________________

Toxins

Tamponade

Tension pneumothorax

Thrombosis (coronary or pulmonary)

Trauma

Even with current advancements in resuscitative technique, prognosis of cardiac arrest is very poor, with only 3-8% of patients being discharged neurologically intact.

References:

  1. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care – Part 7.2: Management of Cardiac Arrest. Circulation 2005; 112: IV-58 – IV-66.
  2. Tintanelli, Judith. Emergency Medicine: A Comprehensive Study Guide. Sixth Edition. (Burgess, Bouzoukis 540-541) McGraw-Hill, 2004.

Toxicology

Musings On Charcoal

By Dr. Bram Dolcourt

Recently I’ve gotten a few “Huh?” thrown my way when I tell people that…

I am actively discouraging the routine use of charcoal for acute overdoses.

The teaching has generally been to give charcoal in the face of an overdose. To many, what I’m saying is a bit surprising. Believe it or not, the American Academy of Clinical Toxicology recommends against routine charcoal use. I thought I’d write a few musings about how and why we recommend using it when we do.

chaos_theory_b

The theory: Activated charcoal has a very high surface area. It will bind and hold a drug (xenobioic), preventing absorption. This will reduce the delivered dose to the patient and reduce toxicity.

Reality: There is very little evidence for the use of activated charcoal. It is occasionally useful and has potential for morbidity. Few patients who claim to have overdosed on a xenobiotic benefit from charcoal.

Who should get it?

For the undifferentiated intoxicated patient, charcoal should only be considered early in the ingestion. Generally, charcoal needs to make physical contact with the xenobiotic in order to absorb it. Once past the pylorus, the chance that charcoal will mix with the xenobiotic is fairly low. The stomach usually empties within 1 hour, although it may be as long as 2. Liquid preparations are absorbed too quickly for charcoal to have significant absorption.stomach

Some xenobiotics may reduce GI motility and prolong the useful window for charcoal. A few authors recommend giving charcoal up to 4 hours post-ingestion. While there is no specific evidence, what is clear is that to have a beneficial effect, charcoal needs to be given early in the ingestion for a non-liquid preparation, generally within 1-2 hours and certainly not beyond 4 hours.

That time frame is for the general case.  There are two other mechanisms of action that allow for alternate dosing for charcoal. First, some xenobiotics are reabsorbed and excreted into the bile (enterohepatic recirculation) or into the stomach (enterogastic recirculation). Charcoal can interrupt this recirculation and reduce the elimination half-life. Secondly, just as dialysis uses a membrane to separate substances from blood, the gut lumen can be used as a membrane to separate substances from blood. Amenable xenobiotics will cross from the blood, across the gut, into charcoal on the enteric side.

There is good evidence for using charcoal for 5 drugs: phenobarbital, carbamzepine, theophyllne, dapsone and qunine (quinidine). These are “Category A drugs.” For these xenobiotics the elimination half-life is reduced when charcoal is given.  Multiple doses of charcoal can further increase the elimination rate for these drugs.

Multidose charcoal works for other xenobiotics, although the evidence is not as good (these are not called Category B drugs, BTW). Phenytoin, glipizide, aspirin (in high concentration), valproic acid, cyclosporine, amitriptyline, and colchicine are all potentially amenable to multidose charcoal.

How much should I give?

Several authors recommend giving 1 g per kg of charcoal, orally. Following this recommendation means that a child who ingests grams of a potentially lethal xenobiotic will receive less charcoal than an adult who eats a few milligrams of something moderately toxic. When placed in that context, it becomes clear the appropriate dose of charcoal should be in relation to the amount of the xenobiotic ingested, with the gram per kilogram being a ceiling dose.

Realistically, you want a 10:1 ratio, gram per gram, of charcoal to xenobiotic for optimal absorption. More is not helpful. Many patients only need a few mouthfuls of charcoal, as opposed to 50 or 100 grams. Consider a digoxin overdose; even for a massive ingestion of 100 tablets, one would likely only need to give 1.25 g of charcaol, which translates to about 6 ml. For a similar ingestion of amlodipine, one would only need to give approximately 50 ml of charcoal, or about 1/5 of the standard dose. It is very clear that we are giving most patients far too much charcoal.

For multidose charcoal, the dosage is less clear. Typically we recommend ½ gram per kg, up to 25 grams, ever 4 hours. This recommendation goes against what I said above. This is probably more than is necessary, however as the indications for multidose charcoal are quite different, we can get away with it.

Why wouldn’t I give charcoal?

All people aspirate to some degree, every day. Usually this isn’t a big deal as it is a small amount. However, in the face an altered mental status or vomiting, people aspirate more. A nasogastric tube also may worsen the risk, as the lower esophageal sphincter is held open. An endotracheal tube may reduce, but does not eliminate, aspiration. The sepsis literature is quite clear that intubated patients still aspirate and I can certain attest to suctioning charcoal out of the ET of many intubated patients.

Charcoal is mostly benign, however it may cause a pneumonitis when aspirated. The additional of sorbitol may worsen the pneumonitis. Charcoal comes in a significant volume; 50 grams of charcoal is usually in 240 ml of total volume. Rapidly instilling this volume can trigger vomiting due to stomach distention. While you want the charcoal to go in as early as possible, rapidly squirting it down an NG tube, can be counter productive and result in respiratory compromise.

pharma_img4

A second and unusual complication may result from too much or two frequent multidose charcoal. In the setting of an ileus, multidose charcoal has resulted in charcoal bezoars. The charcoal was, effectively, compressed into briquettes, inside the gut lumen, resulting in obstruction.

The last complication comes from the sorbitol that is packaged with some charcoal. As there is little evidence for the benefits of using charcoal, there is even less for adding sorbitol (or any cathartic). The idea is that sorbitol increases transit time, removing the xenobiotic more quickly. Sorbitol also increases the total water content of the charcoal stool and may reduce the already small risk of a charcoal bezoar, but is of unproven benefit.

The issue comes about from inducing diarrhea and causing depletion in total body water and electrolytes. One of the ways a xenobiotic kills is by causing cardiovascular collapse. Inducing volume depletion, by osmotically drawing water into the gut, may worsen an already sick patient’s cardiovascular status. Electrolytes travel with water, resulting in an electolyte disturbance. Pediatric patient have developing severe metabolic disturbances from multiple doses of charcoal with sorbitol. Other decontamination strategies, such as urine alkalinization rely on a normal electrolyte profile, and charcoal with sorbitol may actually be counter-productive.

Tell me when I should use charcoal!

Like any drug, the astute clinician must weigh the risks and benefits of charcoal. First and foremost, a clinician needs to consider the lethality and potential morbidity associated with an overdose. Good supportive care has saved more lives than charcoal ever will. I may be so bold as to say that no one has every lived or died purely because of the prompt or lack of application of charcoal. What charcoal may do is moderate toxicity. For a non-lethal or unlikely to be lethal overdose, charcoal may not be needed. For a very lethal overdose, charcoal may reduce the toxicity so that very aggressive and attentive care could save the patient’s life.

Second, the clinician needs to examine the alternate therapies available. If there is a very good antidote or treatment available, charcoal is unlikely to add any benefits; the patient is going to fine either way.

Third, the clinician needs to consider how well the xenobiotic binds to charcoal. For any of the Category A drugs or the other listed medications, charcoal should be strongly considered as toxicity can be reasonably modulated. For metals, such as iron, or electrolytes, such as lithium, there is no potential benefit. For all others, the benefit is questionable.

Finally, patient factors need to be considered. A patient who is unconscious with a tenuous airway, there is a significant risk of charcoal aspiration; especially as an NG tube is needed. An aspiration and charcoal pneumonitis may be worse than the effects of the xenobiotic. Other patient factors to keep in mind: GI anatomy (bariatic surgery), age, co-operation (restraining and forcing down an NG tube on an agitated patient can be problematic), etc.

Can you give me some examples of what you would do?

Keep in mind that these are made up examples and may not encompass all issues, but here goes:

1)            A young patient presenting 1-hour post ingestion of 10-20 tablets of extra strength acetaminophen.

This patient is a possible candidate for activated charcoal. The patient is presenting early and doesn’t have any obvious contraindications.  This would be a 10 gram ingestion, thus using the 10:1 ratio, you would like to give 100 grams of charcoal, but probably can’t due to patient weight. The charcoal may prevent the patient from crossing the “possible toxicity” line on the Rumack-Matthew’s Nomogram, thus you may be able to prevent an admission. This ingestion is unlikely to be lethal and there is a very good antidote, so charcoal is probably not going to reduce morbidity or mortality.

2)            A young patient with a large ingestion of carbamazepine. The patient is sleepy.

I would give this patient charcoal at any point during the ingestion and I would repeat doses every 4 hours. Carbamazepine is a Category A drug and very amenable to charcoal. It is also cardiotoxic, with significant risk for lethality. On the minus side, carbamazepine decreases mental status. The patient’s airway will need to be watched, but this patient will likely benefit from multidose activated charcoal.

3)            A patient presents 1 hour after taking 10-20 risperidone tablets

This patient is not likely to benefit from charcoal and there is potential risk for harm. This is not likely to be lethal ingestion, and if it is, it will be from respiratory compromise or aspiration. Abnormal vitals and other derangements respond well to supportive care. Risperidone is a respiratory depressant, thus this patient may lose the airway with a full stomach, risking aspiration.

4)             A patient who was found down after binging on diazepam and alcohol.

Charcoal is probably not indicated for this patient. This patient is not presenting early and will likely get very little, if any, benefit from charcoal. The patient has a decreased mental status with significant risk of vomiting and aspiration. As long as the patient is breathing, and the airway protected, s/he is at little risk of morbidity or mortality. Endotracheal intubation would likely be the optimal strategy for a patient presenting like this, who needs intervention.

Final thoughts…

Charcoal can be beneficial, but is not the end all treatment for the intoxicated patient. It should be given, not as a reflex, but after careful thought, articulating the expected benefit. The dose should be 10:1 ratio of charcoal to xenobiotic. Charcoal should be avoided when the ingested xenobiotic is not expected to cause morbidity or mortality after other care. The risk/benefit ratio of charcoal needs to be assessed in the context of patients with factors that may predispose to aspiration.

Dr Bram Dolcourt is an Assistant Professor in the Department of Emergency Medicine at Wayne State University in Detroit, MI.  He completed a fellowship in Toxicology in 2009

Answer: quizzer Vol 1.7

quizzER Winners:

Sam Lee                       Brian Junnila                Daniel Seitz

Shereaf Walid             Bindu Vanapalli            Richard Gordon

Katie Ohlendorf          Marjan Siadat               Brian Kern

Kyle Perry                    Claire Jensen                 Maria Pak

Bao Dang                     Devon Moore                 Rob Klever

Last Week’s Question

Answer

The answer is c

The treatment for sepsis has evolved considerably over the past 10 years. Early recognition and early aggressive therapy for patients with sepsis have a significant impact on mortality. Dr Emanuel Rivers et al, brought this issue to the forefront with their landmark article in the New England Journal of Medicine in 2001, where they instituted a treatment protocol for patients with septic shock, termed Early-Goal-Directed Therapy (EGDT). EGDT emphasizes early recognition of patients with potential sepsis in the ED, early broad-spectrum antibiotics, and a rapid crystalloid fluid bolus, followed by goal-directed therapy for those patients who remain hypotensive or severely ill after this initial therapy. Those patients who did not respond to an initial fluid bolus and antibiotics received a central venous catheter in the internal jugular or subclavian vein to measure central venous pressure (CVP) and an arterial catheter to directly measure arterial blood pressure.

EGDT is basically a three-step process, aimed at optimizing tissue perfusion:

  • The first step involves titrating crystalloid fluid administration to CVP, or administering 500 mL boluses of fluid until the CVP measures between 8 and 12 mm Hg. CVP is a surrogate for intravascular volume, as excess circulating blood volume is contained within the venous system.
  • The second step, if the patient has not improved with fluid alone, is to administer vasopressors to attain a mean arterial pressure (MAP) greater than 65 mm Hg.
  • The third step is to evaluate the central venous oxygen saturation (SvO2). This is obtained from the central venous line, which, in turn, is a surrogate for peripheral tissue oxygenation and cardiac output. A central venous saturation of less than 70% is considered abnormal and indicative of suboptimal therapy. In this case, the hematocrit is checked and blood is transfused until a hematocrit greater than 30% is attained. Once this is attained and the central venous saturation is still low, dobutamine is initiated to increase cardiac output.

Systemic Inflammatory Response Syndrome (SIRS)

Sepsis

Severe Sepsis

Septic Shock

Two or more of the following criteria:

  • HR > 90
  • Temperature > 100.4ºF or < 96.8ºF
  • RR > 20, or PaCO2 < 32
  • WBC > 12,000 cells/mm3, or < 4,000 cells/mm3, or > 10% band forms

SIRS

+

Suspected or proven infections

Sepsis

+

Acute organ dysfunction

Sepsis

+

Refractory hypotension

(a) Vasopressor therapy should not be started until the patient receives at least normal saline fluid boluses to achieve a CVP between 8-12 mm Hg or to maintain a mean arterial pressure of at least 65 mm Hg. (b) Packed red blood cells can be transfused if the central venous oxygen saturation (ScvO2) is less than 70 percent, and the hematocrit is less than 30%. However, this occurs after fluid administration. (d) A CVP of 8-12 mm Hg is the goal. Fluid should be administered when the CVP is less than 8 mm Hg. (e) The femoral vein is not a suitable location to place a central line in early goal directed therapy because it does not accurately measure the central venous pressure.

Thank you for everyone who submitted an answer.  Please stay tuned for next week’s quizzER.

quizzER is a weekly contest consisting of a question selected from various areas of emergency medicine that are central to the education of medical students and residents in training.

quizzER Vol 1.7

An 81-year-old woman is brought to the ED by her children who state that the patient is acting more tired than usual, has had fever for the last two days, and is more confused. Ordinarily, the patient is high functioning: she is ambulatory, cooks for herself, and walks on a treadmill 30 minutes a day. Her vital signs are BP 85/60 mm Hg, heart rate 125, respiratory rate 20, temperature 101.3°F, and pulse oxygenation 97% on room air. On examination, the patient has dry mucous membranes, but is otherwise unremarkable. She is oriented to person and place, but states that the year is 1925. Her lab results show a WBC 14,300/µL, hematocrit 31%, and platelets 350/µL. Her electrolytes are within normal limits. Blood glucose is 92 mg/dL. A chest radiograph does not show any infiltrates. Urinalysis reveals 2+ protein, trace ketones, WBC >100/hpf, RBC 5-10/hpf, nitrite positive, and leukocyte esterase positive.  After administering a 500 cc normal saline fluid bolus and broad-spectrum antibiotics through her peripheral intravenous line, the patient’s blood pressure is 82/60 mm Hg. You suspect that the patient is in septic shock. Which of the following is the next most appropriate course of action to manage this patient with early-goal-directed therapy?

a.    Start vasopressor therapy, repeat blood pressure, if below a systolic of 90 mm Hg, increase the dose
b.    Check the hematocrit and if it is less than 30% prepare to transfuse packed red blood cells
c.    Place a central venous line into the right internal jugular vein, measure a central venous pressure (CVP), administer normal saline boluses if the CVP is less than 8 mm Hg
d.    Place a central venous line into the left subclavian vein, measure a central venous pressure (CVP), administer normal saline boluses if the CVP is less than 12 mm Hg
e.    Place a central venous line into the right femoral vein, measure a central venous pressure (CVP), administer normal saline boluses if the CVP is less than 8 mm Hg

Please post your answer in the “reply box” or click on the “comments” link  You will not see your answer post until next week when all of the submitted answers will be posted.  Good luck!

quizzER is a weekly contest consisting of a question selected from various areas of emergency medicine that are central to the education of medical students and residents in training.