Thursday, July 31, 2014

Scorpion Envenomation. Not so bad, but when it bad... is BAD!

Still is summer time and in some parts of the world, scorpions are a threat. There are dozens of varieties to chose from. Here are some basics about the patophysiology of Scorpion Envenomation. From this week's NEJM.




What are the general characteristics of scorpion stings?
Most scorpion stings cause localized pain, whereas only an estimated 10% of stings, even from the most dangerous scorpions, result in severe systemic envenomation. Edema, erythema, paresthesias, muscle fasciculations, and numbness may occur at the site of the sting. It is often difficult to see the sting site or to identify inflammation at the site, despite substantial local pain. Most cases of severe envenomation occur in children. Systemic envenomation is characterized by neuromuscular abnormalities resulting from effects on the somatic and cranial nerves, both cholinergic and adrenergic excitation of the autonomic nervous system, pulmonary edema, and cardiac effects.
What are the autonomic effects of scorpion stings?
Excitation of the autonomic nervous system is characterized by both parasympathetic and sympathetic responses. Parasympathetic, cholinergic effects may include hypersalivation, profuse diaphoresis, lacrimation, miosis, diarrhea, vomiting, bradycardia, hypotension, increased respiratory secretions, and priapism. Sympathetic, adrenergic effects include tachycardia, hypertension, mydriasis, hyperthermia, hyperglycemia, agitation, and restlessness. Whereas most parasympathetic effects tend to occur early, sympathetic effects persist because of the release of catecholamines and are responsible for severe envenomation.
What are possible cardiovascular complications of scorpion envenomation? A range of cardiac conduction abnormalities occur in about one third to one half of patients with systemic envenomation. These effects include atrial tachycardia, ventricular extrasystoles, T-wave inversion, ST-T wave changes, and, less frequently, bundle-branch block. Increased autonomic stimulation caused by increased vagal effects on the heart and sympathetic stimulation are the probable causes of these effects. Hypertension is common and occurs early in response to sympathetic stimulation. Hypotension is less common, occurs with the development of severe envenomation, and often requires intervention with vasopressors and fluid resuscitation. Many factors are at play in the development of hypotension, with cholinergic stimulation causing vasodilation, fluid loss, and myocardial depression. Cardiac dysfunction resulting from catecholamine-induced myocarditis and myocardial ischemia complicates severe envenomation from androctonus, buthus, mesobuthus, and tityus scorpions. This complication may result in pulmonary edema and cardiogenic shock.


What are the principles of treatment for cases of severe scorpion envenomation? The specific treatment is the administration of antivenom combined with symptomatic and supportive treatment, including prazosin and dobutamine in patients with cardiovascular toxic effects and benzodiazepines when there is neuromuscular involvement. Symptoms related to the site of the sting should be managed with appropriate analgesia with acetaminophen and antiinflammatory agents, depending on severity. Once severe envenomation has developed, the administration of antivenom may be less effective, since its primary therapeutic action is to bind toxins; it does not reverse established pathophysiological injury, such as excess levels of catecholamine, pulmonary edema, and cardiogenic shock.
Conclusions
- Scorpion envenomation are rarely fatal, but children are at high risk.
- For most, supportive treatment is fine if no signs of nervous or cardiac system involvement. 
- If is going to be bad, it goes from bad to worse very quickly. Therefore, if antivenom is available, give it early and transfer sooner rather than later.
- Prazosin, an alfa blocker, and dobutamine in combination for patients with cardiovascular symptoms. And benzos for neuromuscular involvement.
- Not all scorpions are scary, some can also be cute... like this one!



Monday, April 14, 2014

Hypersensitivity to Hymenoptera Sting... Not a Little Problem !

Spring is here and with that, the return of the hymenoptera stings coming to the ER. So we are going to review this week's NEJM article on the topic using the question and answer format.


What is the antigenic cross-reactivity between Hymenoptera species?
The Hymenoptera insects whose stings cause allergy are generally from three families: Apidae (honeybees and bumblebees), Vespidae (hornets, wasps, and yellow jackets), and Formicidae (fire ants). The molecular characteristics of the venoms from the three families of Hymenoptera are sufficiently different that there is very little antigenic cross-reactivity. Within families (e.g., vespids), there can be substantial cross-reactivity among the allergens present in the venoms; however, honeybee and bumblebee allergies are distinct.


What is the pathophysiology of an allergic reaction to a hymenoptera sting, and how common is an anaphylactic reaction?
In sensitized persons, a sting can cause the injected venom to bind to venom-specific IgE on mast cells, cross-linking high-affinity IgE receptors and subsequently leading to the rapid release of mast-cell mediators, including histamine, leukotrienes, prostaglandins, and platelet-activating factor. The released mast-cell mediators can cause a spectrum of allergic reactions, from local reactions (affecting small or large [≥10 cm] areas) or urticaria to anaphylaxis and even death. Patients with large local reactions usually do not have a systemic reaction to subsequent stings (with systemic reactions occurring in <10% of these patients), nor do children with isolated urticaria. However, a previous systemic reaction in a patient with venom-specific IgE is associated with a high risk of subsequent systemic reaction, which may occur in 30 to 60% of these patients. Anaphylaxis due to a hymenoptera sting causes at least 40 deaths per year in the United States, although this number is probably an underestimate. Severe systemic allergic reactions occur in approximately 0.4 to 0.8% of children and 3.0% of adults.


What are the risk factors for a severe reaction to a hymenoptera sting and how should it be treated?
Acute systemic reactions typically occur very rapidly after a hymenoptera sting but may be delayed for several hours or be biphasic. The factors associated with an increased risk of severe reaction include being stung by a honeybee (greater risk than with other hymenoptera), underlying mast-cell disorders with elevated serum-tryptase levels at baseline, a previous severe reaction, preexisting cardiovascular disease, and concomitant treatment with a beta-blocker, angiotensin-converting–enzyme inhibitor, or both. Anaphylaxis can present with a spectrum of signs and symptoms affecting multiple organ systems, including the skin, gastrointestinal tract, cardiovascular system, nervous system, and both the upper and lower respiratory tracts; hallmarks of anaphylaxis are the development of hypotension or the involvement of more than one organ system. The treatment of anaphylaxis in the emergency department should include epinephrine for any patient who has more than cutaneous symptoms; epinephrine should also be considered in adults with urticaria alone. H1-antihistamines can help relieve cutaneous signs and symptoms. For respiratory symptoms, supplemental oxygen and inhaled beta2-agonists should be used. For patients with hypotension, volume resuscitation is indicated, with 1 to 2 liters of 0.9% (isotonic) saline infused rapidly (e.g., a dose of 5 to 10 ml per kilogram in the first 5 to 10 minutes in an adult, and 10 ml per kilogram in a child).

Who should receive venom immunotherapy?
Subcutaneous immunotherapy should be considered in all patients who have had a systemic allergic reaction to an insect sting and who have a positive skin test or a positive result on an in vitro test for venom-specific IgE antibodies. Children 16 years of age or younger who have had isolated cutaneous systemic reactions to insect stings have a very low risk of subsequent reactions and do not require venom immunotherapy. Venom immunotherapy is also generally not necessary in patients who have had only a large local reaction, because their risk of subsequent systemic reactions is relatively low. However, patients with unavoidable or frequent exposures (e.g., beekeepers) may benefit, because observational data indicate that, after immunotherapy, local reactions are reduced in size and duration.

Key points to remember:
- Hymenoptera stings CAN kill, so take them seriously, specially those with prior severe reactions and honeybee stings.
- It is an IgE hypersensitivity reaction, therefore it is fast in most cases, but don't forget it can be biphasic.
- High risk are patients on beta blockers, ACEI and cardiovascular disease, the very young and old.
- Anaphylaxis is hypotension plus one other system involved: Skin, GI, respiratory or neurologic. Don't miss it !
- If it looks bad... IS bad. Get epinephrine IM mas rapido and quickly start an epinephrine drip and ensure good volume resuscitation. Antihistaminics, steroids and beta agonist are secondary agents.
- Arrange for follow up in all severe cases for possible immunotherapy, let the PCP and allergist make that call.
- Don't forget your dog... consult the vet right away! '',




Thursday, March 13, 2014

Management of Skin Abscesses. NEJM review article

From this week's NEJM... some guidelines in how to treat this common problem.


Clinical Pearls
How does ultrasound enhance the diagnostic accuracy of physical exam in detection of an abscess?
Studies in adults and children suggest that soft-tissue ultrasonography enhances the diagnostic accuracy of abscess detection and alters plans for management that are based on physical examination alone. In a prospective study involving 126 adults with clinical cellulitis in whom an emergency physician believed an abscess was not obvious on physical examination but might be present, ultrasonography resulted in a change in projected management in 56% of the patients. Ultrasonographic images showed fluid collection that was consistent with an abscess in half these patients, and approximately 80% of patients who underwent additional diagnostic testing had pus or other fluid collections. Management was also altered in three quarters of patients in whom drainage had been thought to be required on the basis of physical examination alone (e.g., it was decided that drainage was not needed, that further imaging was required, or that the incision and drainage approach should be altered).
What are the general principles of incision and drainage of an abscess in the office setting?
Many abscesses can be managed in the office setting by a general practitioner. Large, complex, or recalcitrant abscesses, especially those over sensitive areas (e.g., the hands or face), should prompt consideration of referral to a specialist or an emergency department, where additional resources can be brought to bear. The primary treatment for skin abscesses is incision and drainage. A single incision is made; the incision should be long enough to ensure complete drainage, allow lysis of loculations with a blunt instrument, and follow tension lines in order to minimize scarring. A common mistake is to make an incision that is not deep enough to reach and fully drain the abscess cavity. Particular care should be taken before incising the skin over critical structures, such as major vessels and nerves. A recent small study among adults suggested that many abscesses can be adequately drained through a short incision (median length, 1 cm).
Q. According to the authors, when should primary closure of drained abscesses be considered?
A. Primary closure of drained abscesses should be considered for large incisions (i.e., >2 cm), especially over cosmetically important areas, and may warrant referral to a specialist. Primary closure should not be performed in patients with infected sebaceous cysts or lymph nodes or similar disease processes, patients in whom the adequacy of drainage is in doubt, and patients who have systemic infection or a strong risk factor for systemic infection (e.g., diabetes).
Q. When is antibiotic treatment recommended in addition to incision and drainage of an abscess, and in such cases, what is the appropriate antibiotic regimen?
A. The Infectious Diseases Society of America (IDSA) recommends systemic antibiotic treatment, in addition to incision and drainage, for patients with severe or extensive disease (e.g., multiple sites of infection) or with rapid disease progression and associated cellulitis, signs and symptoms of systemic illness, associated coexisting conditions or immunosuppression, very young age or advanced age, an abscess in an area difficult to drain (e.g., face, hands, or genitalia), associated septic phlebitis, or an abscess that does not respond to incision and drainage alone. Empirical antibiotic therapy, if prescribed, should have in vitro activity against community-associated MRSA. Most patients who have a minor abscess can be treated as outpatients with inexpensive oral antibiotics. TMP-SMX, clindamycin, and tetracycline have been shown to have in vitro activity against 94% to nearly 100% of more than 300 MRSA isolates tested in a 2008 U.S. emergency department–based surveillance study. Other antibiotics with anti-MRSA activity that have been approved by the Food and Drug Administration for the treatment of skin and soft-tissue infection include vancomycin, linezolid, daptomycin, telavancin, tigecycline, and ceftaroline.

Worth emphasizing:
1) Incision and drainage is the primary treatment for skin and soft tissue abscess.
2) Consider referring if abscess is located in complicated or cosmetically sensitive areas.
3) Antibiotics ONLY for complicated or high risk cases.
4) Cheap antibiotics are just fine.

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In another note… I want to thank my new friends at Cho Ray Hospital in Ho Chi Minh City for hosting such a great event. I look forward to next year’s conference.





Thursday, January 30, 2014

DKA and Cerebral Edema. Are Fluids to Blame or is it Shock?

It's almost the end of the month and I am again behind schedule. But today I have something controversial and very interesting... Pediatric DKA. In particular the issue about fluid administration and risk for cerebral edema.




Pedi DKA is scary, dangerous and subject of heated debate when it comes to fluid administration. Most of the treatment protocols in pediatrics are very stingy when it comes to fluid administration. In severe cases, kids arrive in shock, hypotensive, tachycardic, severely vasoconstricted, and many of them comatose; the protocol says to give them just 10 ml/kg bolus and correct remaining deficits over 48 hrs. This doesn't make  sense to me. If you are in shock, you are not perfusing! Why would I want to drag the treatment of someone in shock? I have seen my fare share of sick pedi DKA's and the ones in the severe end of the spectrum look just like that, awful. In England you cannot give a 20 ml/kg initial bolus to a DKA kid in shock without being called to the medical director office and ordered to memorize the protocol and recite it the next day in front of everyone to hear.  The notion that rapid fluid administration is the cause of cerebral edema in severe DKA is so engraved in all the treatment protocols, but there is no solid evidence to support this idea, except for observational studies and consensus recommendations. I was really bothered by this and tried to find the science behind and found that it is not the fluid rate what is associated to the risk of cerebral edema, is the level of dehydration, acidosis with hypocapnia, hyperglycemia and brain hypoperfusion what causes all the problems. The kids who are going to develop cerebral edema are in the sickest end of the spectrum, probably arrive with cerebral edema and will become clinically obvious regardless of the fluid infusion rate. 

Last year, in the journal of Pediatrics (http://pediatrics.aappublications.org/content/131/1/e73) there was a RCT of 18 kids (I know is a small number, but this is randomized human data rather than rat studies). One group received 20 ml/kg bolus with correction of dehydration over 24 hrs. The second group received a 10 ml/kg bolus and correction of dehydration over a 48 hr period. The results showed no difference in MRI cerebral edema parameters at different treatment stages between the rapid fluid replacement approach compared with the slower infusion rates approach; and more importantly, MRI findings were consistent with vasogenic edema and were worse at the beginning of treatment compared with after-treatment in both groups. This suggests that sick DKA kids already have cerebral edema before initiation of therapy and edema improves after treatment independently of fluid infusion rates. Those who support the idea that rapid fluid infusion is the cause of cerebral edema in DKA treatment, say that it is due to rapid osmotic changes (we all have heard that), and there is probably some true about that. However, one important distinction to make here, is that osmotic cerebral edema and vasogenic cerebral edema are not the same. The TBI research (http://www.ncbi.nlm.nih.gov/pubmed/15561417shows that vasogenic cerebral edema is due to blood-brain barrier disruption resulting in extracellular water accumulation. In the other hand, osmotic cerebral edema is caused by osmotic imbalances between blood and brain tissue. These kids who got MRI early, all had vasogenic edema. How is that different by MRI? - I have no idea, but I am sure the radiologist have.

In regards to the factors that predict the development of cerebral edema, there is a great article from the NEJM from 2001, comparing 265 children with severe DKA. This study puts it all together very nicely. (http://www.nejm.org/doi/full/10.1056/NEJM200101253440404) Some children developed cerebral edema and some did not. Analysis of other biochemical markers showed something very interesting. "Although osmotic factors and other mechanisms may play a part in the development of cerebral edema, our data lend support to the hypothesis that cerebral edema in children with diabetic ketoacidosis is related to brain ischemia. Both hypocapnia, which causes cerebral vasoconstriction, and extreme dehydration would be expected to decrease perfusion of the brain. In addition, bicarbonate therapy causes central nervous system hypoxia in laboratory animals with diabetic ketoacidosis. Hyperglycemia superimposed on an ischemic insult increases the extent of neurologic damage, blood–brain barrier dysfunction, and edema formation. This interaction might help to explain the occurrence of neurologic damage in association with minor degrees of cerebral hypoperfusion. Blood–brain barrier dysfunction and vasogenic edema may occur several hours after an ischemic insult as a result of the release of vasoactive substances and mediators of inflammation. The occurrence of cerebral edema several hours after the initiation of therapy thus correlates well with the hypothesis that the basis of this complication is ischemia. Finally, the more frequent occurrence of cerebral edema in children than in adults may be explained in part by the fact that children's brains have higher oxygen requirements than adults' brains and are thus more susceptible to ischemia".


A good while ago, Canadians also found that low CO2 and high BUN had the strongest association with cerebral edema (http://linkinghub.elsevier.com/retrieve/pii/S0022347604012168?via=sd). Again.. these are sick DKA kids. This was a case control study, after adjusting for variables, found not association between the occurrence of cerebral edema in DKA and treatment factors. The authors conclude that the presence of cerebral edema before treatment of DKA and the association with severity of illness suggest that prevention of DKA is the key to avoiding this devastating complication. 


Summarizing... Here are the strongest associations with their respective OR's, CI and P values



  • Initial BUN (per increase of 9 mg/dl): 1.8 (95% CI: 1.2-2.7); p value 0.008
  • Initial partial pressure of arterial carbon dioxide (per decrease of 7.8 mm Hg): 2.7 (95% CI: 1.4-5.1); p value 0.002
  • Treatment with bicarbonate: 4.2 (95% CI 1.5-12.1); p value 0.008 (Don't do it!)
  • Rate of increase of serum sodium concentration (per increase of 5.8 mmol/l/hr):0.6 (95% CI: 0.4 - 0.9); p value 0.01
Conclusions
- Cerebral edema in the setting of DKA is more related to the severity of the primary disease process rather than the rate of fluid treatment. The pathophysiology is complicated, but hypoperfusion leading to cerebral ischemia along with damage to the blood-brain barrier all result in vasogenic edema. 
- Pedi DKA in shock -> Treat shock !  Their brain needs perfusion. However, be cautious and don't flood this kids with fluids, just restore tissue perfusion. Some guidelines (mostly from the U.S.) suggest an initial bolus of 20 ml/kg is a reasonable start point in shocky kids, with the option to repeat if there is no improvement in hemodynamics. However, a maximum of 30-40 ml/kg in the first 4 hrs of treatment is recommended with early consideration of sepsis if no response. This is when being a good clinician is so important. 
- Don't give bicarbonate, don't give bicarbonate and don't give bicarbonate. Is that clear enough?
- Having a healthy skepticism and questioning the old dogmas may get us closer to the truth about what is the right thing to do.