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Core Content Show Notes:
Here we review three major antihypertensive- Beta Blockers, Calcium Channel Blockers, and Clonidine- who share a similar toxidrome. The way these meds with present in overdose is bradycardia and hypotension.
Basics of neurotransmission: There really are only 3 components you need to know about this complex biochemical process to understand meds. These are the presynaptic cell, the neurotransmitter, and the post-synaptic cell. Here we apply this to how the body maintains blood pressure and cardiac output:
Now let’s talk about the specific agents.
Mechanism of Action: blocks the first step in this chain reaction. Stimulating α2 receptors in the CNS affects the presynaptic cell. This decreases the output of Epi/NE into the blood stream.
Distinguishing clonidine from BBs and CCBs: As we said, all these agents will have bradycardia and hypotension. The non-BP related effects are where you see the difference in the agents. Clonidine also hits the locus coeruleus (don’t need to remember this) in the brain, and causes an opioid-like syndrome of miosis, lethargy and respiratory depression
Beta Blockers (BBs)
Mechanism of Action: blocks the β1 receptors on our myocytes. The Epi/NE are in the blood stream, but do not get to have their post-synaptic effect.
Distinguishing BBs from others: Because they work on β receptors, there can be cross-reactivity in toxicity (at what level depends on medications selectivity β1 vs β2). The β2 effects are seen as bronchospasm, especially in patients with reactive airways. Blocking Epi in the liver with also result in decreased gluconeogenesis and can hypoglycemia.
Calcium Channel Blockers (CBBs)
Mechanism of Action: blocks the Ca2+ channel, that last step in the cascade where increased concentration of Ca2+ in the myocyte leads to increased inotropy.
Distinguishing CCBs from others: CCBs affect the same Ca2+ channel on other organs, including the pancreas. Blocking these channels in the pancreas decreased insulin secretion, leading to hyperglycemia.
Generally, in terms of symptom severity it goes from clonidine < Beta Blocker < Calcium Channel Blocker in terms of severity.
General principles of toxicology apply, which include: decontamination, enhanced elimination, and antidotes. For our antihypertensives, you can use activated charcoal and whole bowel irrigation, depending on the time frame. There are no real means of eliminating these agents more quickly.
Again, generally a “mild” overdose, clonidine often does not have the severe bradycardia or hypotension of the others. Interestingly, atropine is not a good agent in this overdose. This is because atropine works by decreasing parasympathetic (vagal mediated) tone, with the hopes of unopposed sympathetic tone leading to increased heart rate and blood pressure. But as we know, the sympathetic system is being blocked at the level of the brain stem, so no dice.
But if you move down the cascade, you arrive at Epi/NE which still have open, normal β1 receptors and downstream effects. Giving some exogenous Epi/NE gets the cascade back on track. You can also try to increase the calcium gradient at the level of the Ca2+ channel simply by giving calcium. This can work, but the effect is moderate at best.
Now, if we go off what we’ve learned, we no atropine isn’t going to help much. Epi/NE work for clonidine, but we are blocked one step further down the cascade, at the β1 receptor, so Epi/NE can be given in heaps but there is no receptor to act on. Giving calcium to increase the transcellular gradient still works, and is still with limited benefit.
But wait! There is another receptor on our myocytes that also increases cAMP, just like β1!! It’s the glucagon receptor. cAMP is cAMP and works on the Ca2+ channel just the same, no matter where it came from. So by giving glucagon you can bypass the β1 receptor and still get your Ca2+ into the cell.
Calcium Channel Blockers (CCBs)
Now we’re at the end of the line. The Ca2+ channel is blocked and no amount of atropine, Epi/NE, calcium, or glucagon is going to open it. So, what do we do?
Hyperinsulinemia-Euglycemia (HIE): why this stuff works is complicated/not fully understood. Maybe it’s because the heart in a stressed state uses carbohydrates more, and HIE increased carbs available. Maybe it’s that insulin can sneak more Ca2+ into the myocyte. Maybe it’s magic. Maybe it’s Maybelline. Either way, it works. And all you need to remember is 1 U/kg. That is the bolus and hourly rate.
Intravenous Lipid Emulsion (ILE): Putting a bunch of lipids in the blood seems to work. Why? Maybe it’s a lipid sink, absorbing the CCB, removing it from the active site. Maybe it’s an alternative form of myocyte energy. Again, the physiology is unclear. To use this call your pharmacist, but generally is 1.5 ml/kg bolus and 0.5 ml/kg. The efficacy and safety of this treatment for CCB is not as well established as HIE, so use this with caution.
Cunningham Shoulder Reduction- Core Content
Shoulder reductions and the various techniques can get confusing. Everyone and their mother has come up with some way they think is best to reduce this dislocated joint. Here we discuss a new(ish) type of reduction that does not require procedural sedation- the Cunningham technique. First, a little review.
The shoulder is the most commonly dislocated joint. It has evolved to have insane range of motion in multiple planes. But with this mobility comes instability. The dome of the Humerus sits in a very shallow cup of the glenoid. Lets review some anatomy quickly.
The shoulder joint in its brass tax is composed of the humeral head sitting in the glenoid fossa of the scapula. The scapula has two other important boney prominences involved in the shoulder’s architecture- the coracoid and the acromion. The acromion articulates with the clavicle the (technically) third bone of the shoulder. Along this U shaped articulation the deltoid and trapezius muscles attach. The coracoid has a strong coraco-acromion ligament as well as a coracoclavicular ligament. It also is the insertion point for the biceps brachii and the pec minor.
When the humeral head dislocates from the glenoid, the shoulder often takes a classic “step off” appearance with a flattening of the deltoid. The patient will often keep that arm fully adducted against the body with the forearm across the abdomen.
The shoulder can dislocate in three directions- anteriorly, posteriorly, and inferiorly. The anterior dislocation is by far the most common- representing >90% of all dislocations. Mechanistically, it is often with the arm abducted and externally rotated. Think of a quarter back about to throw a pass. This is the most vulnerable position. Posterior dislocations are classically taught to occur after seizures or electrocutions, where there is abnormal muscular contraction, but practically this is often a fall on an internally rotated outstretched arm. The inferior dislocation, the white whale of shoulder dislocations, occurs in 0.5% of dislocations and is the result of an axial load on the shoulder. This is also called luxatio erecta and presents with the arm stuck in abduction.
In this clinical case we present an intra-articular block/anesthesia and Cunningham reduction. Let’s discuss the shoulder block here. There are two approaches to the shoulder block: anterior and posterior.
Anterior: In this approach, you are using the coracoid process as your boney landmark. The shoulder is rotated externally and you palpate the head of the Humerus. The needle is inserted just medially to the humeral head staying slightly inferiorly and laterally to the coracoid process.
Posterior: In this approach, we are using the acromion as our boney landmark. The patient is in neutral position. The sulcus between the humeral head and the acromion is palpated. The needle is then inserted 2-3 cm the most inferio-medially part of the acromion.
Now, is using intra-articular lidocaine without procedural sedation to reduce someone’s shoulder inhumane? In short, no. As proof, Fitch et al. did a systematic review of 6 papers comparing procedural sedation to intra-articular lidocaine and found no difference in pain or reduction success rate. There were, however, more complications in the full sedation group.
A clinician can get overwhelmed with all of the possible reduction techniques out there. The ideal technique is one that is painless, requires only one practitioner, uses minimal force, and no IV sedation. Through the many attempts of proving one technique superior to the others, no one has risen to the top in the literature. The AAOS also does not endorse one technique over the others.
Today we are going to talk about the Cunningham. This is a technique that was first published on in 2003 by Dr. Neil Cunningham In the Emergency Medicine Australasia. The technique is completed by doing the following:
Have the patient sit in a comfortable position (sitting, adducted arm, elbow flexed)
Place the patient’s hand on your shoulder (if able)
Place your hand in the patient’s in elbow crease
Apply gentle downward pressure
Ask the patient to pull their shoulder blades together
Massage the shoulder/bicep musculature
Add gentle external rotation as needed
Success rates for this technique vary and this is little published literature on unselected patients. The bottom line is this is going to require a relaxed, not hyperaesthetic with a relatively thin frame (you need to over-come the muscles) and preferably not be out that long. The longer the dislocation, the more fixed the spasm.
Acad Emerg Med. 2008 Aug;15(8):703-8.
BLUNT TRAUMA ARREST
Core Content Show Notes
Henderson Paper: ‘94 California. Looked at registry of cardiac injury patients. 251 patients. Looked to find predictors of survival. Had 14% blunt injuries, but NONE underwent thoracotomy. Patients with +VS had a 62% survival, -VS had <1%. Note that not all patients underwent ED thoracotomy. 122 ED thoracotomies done, 4.9% overall survival. 110 of EDTs done on patients with PI of 20, and these had <1% survival. Paper found, like others had, that Physiologic index was the best predictor of survival and that GSW to the heart is bad for one’s health.
Durham Paper: ’92 Texas. Retrospective review of thoracotomies over a 6 year period. Specific focus was on prehospital interventions that improved survival. 389 patients, 53% GSW, 29% stab, 18% blunt. Survival: 15% for stab, 7% for GSW, 0% for blunt. Major finding among survivors was that intubated patients had a mean CPR time of 9 minutes vs 4 minutes for nonintubated patients. Basically, intubating the patient prehospital doubled your time window to preform EDT.
Lorenz Paper- ’92 California. Retrospective review of 10 years of cases from 1980-1990 with 463 total patients. Looked at the predictors of survival. They had a 22% survival for penetrating trauma (8% for GSW and 34% for stab) and a 2% survival for blunt. There were several patients with no SoL in the field who underwent EDT (remember, 1980s). None of these survived. One conclusion was that EDT should be withheld in these patients, and it now is. In dissecting the blunt arrest patients more, it turns out of the 2% survivors (3 patients), only 1 underwent EDT and the other 2 underwent operative sternotomy. Given the reported survival percentage, Lorenz concludes blunt trauma arrest is a relative contraindication to EDT. Collectively this paper reports improved survival of stabs over GSWs, and better survival in patients with higher physiologic indices.
Hunt Paper- ’05 Ohio. Site doesn’t matter here because this paper reviews the history of EDT, the pathophys of thoracic trauma, etc. Worth noting that blunt chest trauma results from deceleration or crush and results in hemothorax, heart/lung contusions, and disruption of the great vessels (bell clanger). Paper then goes into PI and cites Henderson.
Lockey Paper: ’12 UK. Essentially a paper presenting an algorithm. Lockey et al mention 18 years experience with thousands of patients, then present a skematic of how they proceed. There is an emphasis here on pre-hospital thoracotomy, as their system as physician-led EMS units. This paper does not present data supporting this. Also introduces HOT (hypovolemia, oxygenation, tension ptx) in the algorithm.
Burlew/WEST guidelines- ’12. The WEST recommendations state a use of the available data and reports on EDT, though specific numbers are referenced only for survival rates in different circumstances. Largely an expert consensus paper and they are clear about this. WEST produces a simples to follow algorithm (Fig 1) with the following components: CPR with no signs of life (SoL) [motor/resp effort, electrical activity, pupillary response] gets divided by injury and time. Penetrating trauma with >15 min CRP is called. Blunt Trauma with >10 min CPR is called. If you’re in the time window, do the EDT. They cite survival rates of 15% for penetrating trauma and for blunt it is 2% if in shock and <1% if no SoL. They DO recommend EMS do CPR, as well as intubate and transport quickly. They go on to state that once in the chest, patients without cardiac injury or tamponade with asystole should be called. If after all resuscitation is preformed the patient cannot maintain a SBP > 70, the patient is deemed nonviable and resuscitation is ended.
Inaba paper- ’15 California. Prospective study of 187 patients undergoing EDT. All got parasternal and subzyphoid views before or during thoracotomy. They found that all survivors (true survivors and organ donors) had cardiac activity on US. Patients’ with pericardial fluid seen on US did not survive. Interestingly, no patients with a cardiac injury survived, which is somewhat contradictory to the physiologic argument for the EDT in the first place. In their conclusions, they state that in patients with no cardiac activity or pericardial fluid on US survival was zero. This somewhat lumps the pericardial fluid finding in with the more clinical significant finding of cardiac activity.
Rhee Paper- ’00. This is the systematic review paper. Rhee and colleagues looked at the prior 25 years of data on EDT and reviewed it. 24 papers of appropriate quality were found and the associated 4,620 patients formed the basis of analysis. Overall survival of EDT was 7.4%. Broken down by mechanism, it was 1.4% for blunt and 8.8% for penetrating, which was further subdivided into 16.8% for stab and 4.3% for GSW. Rhee also looked as SoL (resp effort, electrical activity, pupillary response). They found patients who had SoL in the hospital had an 11.5% survival, versus 2.6% for those without.
Seamon/EAST paper- ’15. A more systematic and scientific look at the literature than the WEST guidelines. This paper did a PICO analysis of specific questions related to EDT and collectively reviewed 72 studies and 10,000+ patients to base their recommendations on. Six questions were formulated based on the following criteria: with/without SoL for penetrating thoracic/penetrating extrathoracic/blunt injuries. They defined SoL as pulse, BP, motor/resp effort, pupillary response and cardiac electrical activity. To simplify the results, I present them in bullet form:
*They do not put a definitive timeframe for this, but mention the 15 minute window discussed in other studies.
+No definitive timeframe outlined.
Rh Alloimmunization- Core Content
When to use Rhogam and at what dose, while seemingly a straightforward subject, can be confusing. In this Core Content we review some brief epidemiology on Rh status, discuss the consequences of Rh alloimmunization, review what Rhogam is, and finally when to use it.
We can remember from medical school that peoples’ red blood cells (RBCs) either have an Rh antigen (also called Rhesus factor or D antigen) or they do not. People without the antigen will therefore recognize the Rh antigen as foreign if it is in their body/blood. The resultant immune response creates antibodies to the Rh antigen, just the same as it would a viral or bacterial antigen.
But how common is this, really? According to the Rhogam website1, the prevalence is variable by race. They give the following table:
Other resources site more general numbers, with Rh negative status being 15% of the population as a whole.2 BMJ best practices actually sites very similar numbers to the Rhogam website, with ~15% for white, ~7% for black, and <1% for Asian and Native American.3
This is the devastating consequence we are trying to avoid. It is VERY important to recognize that the risk does not occur with the first exposure to the Rh antigen. Compare it to an allergy to bee stings, you dont get anaphylaxis with the first sting. Your immune system has to build its antibody army first. It is then with subsequent stings that things start going wrong.
The same is true for Rh alloimmunization. The maternal circulation must first see the Rh antigen, recognize it as foreign, and build an immune response to it. This can happen during blood transfusions (not really anymore) and, more commonly, exposure to Rh+ blood during the course of a pregnancy from any number of causes (delivery, miscarriage of any variety, OB procedures, abruption or other trauma, etc).2 How much blood is needed to sensitize is actually not well understood, but some studies show as little as 0.1 mL.2,5 Most sensitization events are thought to be deliveries, where the mother is exposed to the largest amount of fetal blood. Therefore, it is usually not the first born Rh+ kiddo who is the problem but subsequent pregnancies.
Once the fetomaternal hemorrhage occurs, mom’s immune system makes antibodies to the Rh antigen. It is thought that it takes a while for there to be a clinically significant immune response mounted. Again, studies vary from 4 up to 15 weeks.2,5 Once made (or more commonly present in mom ever since the last kid), it is specifically the IgG that crosses the placenta and will start attaching itself to the fetal RBCs.4 This leads to the RBCs destruction in the fetal spleen.
The effects of Rh alloimmunization
The opsonization and destruction of fetal RBCs in their own spleen leads to a profound anemia. The discussion of its recognition and monitoring in utero is beyond the scope of this talk. The significant anemia leads to the fetus having hydrops fetalis, characterized by severe edema and technically consisting of at least two of the following: ascites, pleural effusions, skin edema, and pericardial effusion.5,6 The care and management of a fetus both in utero and post-delivery is complex and mortality rates are high.
Hydrops fetalis is a disease much more easily avoided than treated. To prevent the alloimmunization, science has created Rh-D immune globulins, best known under the trade name Rhogam. This medication is preformed antibodies to the Rh antigen. The physiology behind its functioning is that the Rh-D immune globulins administered to a pregnant patient will find and sequester the Rh antigens that entered maternal circulation during the fetomaternal hemorrhage.
How to use it
The first step to preventing Rh alloimmunization is to think to do so. While our colleagues in Obstetrics and Gynecology are trained to be hyper-vigilant in this regard, consideration of Rhogam is not always high on our priority list. Rh– women are given Rhogam 300 µg at 28 weeks gestation and within 72 hours of delivery by our OB colleagues.7
For our purposes, we need to know when to give the Rhogam and how much to give. The following conditions are considered times in which fetomaternal hemorrhage may occur, and hence, when Rhogam is indicated: Threatened or spontaneous/induced miscarriage, blunt abdominal trauma, ectopic pregnancy, fetal death (2nd or 3rd trimester), antepartum hemorrhage (abruption or previa), and molar pregnancy.7,8 The American Colleague of Obstetrics and Gynecology (ACOG) and UpToDate are in agreement in this list.
In terms of dosing, the “full dose” of Rhogam is 300 µg, and is thought to be effective at suppressing immune response to ~30 mL of fetal blood Rh+ blood. A smaller, 50 µg dose is effective against 5 mL of fetal blood. It is only after 20 weeks gestation that the entire fetal circulation is 30 mL of blood. Therefore, after this timeframe the 300 µg dose may actually be inadequate, depending on how much fetomaternal hemorrhage occurred.8 ACOG makes specific mention of quantifying fetomaternal hemorrhage in cases of placental trauma.7
In the first trimester, there are many who recommend the 50 µg dose, citing that at 12 weeks the fetal circulation contains ~5 mL blood.8 ACOG, however, recommends a 120 µg dose and states its actually ok to give the more readily available 300 µg dose.7
Importantly, using Rhogam in a Rh+ patient is not thought to be harmful, though generally should be avoided.8
ALCOHOL WITHDRAWAL DEEP DIVE SHOW NOTES
Visual Aid created for Benzos in the Healthy Liver vs Cirrhotic.
Notes from Bryan Hayes on material discussed:
Contraindications for outpatient therapy: https://www.ncbi.nlm.nih.gov/pubmed/15706731
ALiEM post on benzos: https://www.aliem.com/2013/all-benzodiazepines-are-metabolized-by-the-liver/
ALiEM post on dexmedetomidine: https://www.aliem.com/2013/dexmedetomidine-precedex-as-adjunct-for/
Handout from SMACC talk on severe EtOH withdrawal: https://pharmertoxguy.files.wordpress.com/2016/07/hayes-2015-smacc-beyond-benzos-for-alcohol-withdrawal-handout.pdf
Phenobarb articles: https://www.ncbi.nlm.nih.gov/pubmed/1986421, https://www.ncbi.nlm.nih.gov/pubmed/22999778, https://www.ncbi.nlm.nih.gov/pubmed/17255852
Maryland EtOH withdrawal protocol:
Updated and Reviewed: March 2009, December 2013.
Reviewed By Siu Yan Amy Yeung, Pharm.D.; Christopher Welsh, MD; Carl Shanholtz, MD; Mangla Gulati, MD
Core Content Show Notes
Alcohol withdrawal is an issue faced in nearly every Emergency Department. What we are going to review here is the physiology of withdrawal, who is most at risk for severe symptoms, and how to manage the withdrawing patient on all levels of the spectrum from the shakes to florid DTs.
Alcohol (EtOH) withdrawal is obviously incredibly common, and it is estimated that ~1/2 million people in the US get pharmacotherapy for symptoms of withdrawal each year.2 To understand this, first let’s talk about what EtOH does to the brain.
Alcohol causes a one-two punch on important neurotransmitters in the brain- GABA and glutamate. Think of GABA as the breaks (inhibitory neurotransmitter) and Glutamate as the gas (excitatory neurotransmitter). EtOh is a neuro suppressant because it enhances GABA (slams on the break) and inhibits glutamate (takes the foot off the gas).
Because the body doesn’t want your life to pass by in a coma, when alcohol is chronically present in the blood, it will up regulate glutamate and down regulate GABA to allow the chronic alcoholic to be alive and walky talky with higher and higher blood alcohol levels.
So now the stage is set for abrupt withdrawal. The severity of withdrawal depends on the chronicity of their alcohol abuse, how much they drink per day/sitting (ie average blood alcohol level), and if they ever have periods of abstinence. Genetics is also thought to possibly play a role.3
Before we delve into symptoms and spectrum, let’s briefly discuss concurrent conditions and get that out of the way. The withdrawing alcoholic has the potential for many concurrent disease processes that can confound and need treatment. Quickly, here they are:
Dehydration- EtOH has a diuretic effect and will often replace water as the PO liquid of choice. If the patient is vomiting that can increase this volume depletion.
Hypoglycemia- poor nutrition and low glycogen stores can lead to this.
Low thiamine- this is the classic definiency, thought to be nutritional, that precipitates a Wernike’s encephalopathy.
Hypomagnesaemia- etiology to this is likely similar to above (diuresis, nutritional deficiency), but some Canadian research has shown the most common cause behind hypomagnesemia was severe chronic alcoholism.4 Others, however, have questioned the validity of this.7
“Minor” withdrawal symptoms: Autonomic instability is the name of the game in EtOH withdrawal. The question is how bad. In the minor withdrawal patient, they will have the first signs of this, which include:
Anxiety, epigastric discomfort, tremulousness, diaphoresis, tachycardia and hypertension.4
These patients have a normal mental status. Timing for these symptoms is usually within 6 hours of EtOH cessation.
“Moderate” withdrawal symptoms:
These include further/more severe autonomic instability- significant tachycardia/hypertension, tremor affecting motor function, etc. Really, the next ‘step” if you will in severity of alcohol withdrawal is progression to seizures and hallucinations. Let’s talk about each individually:
Hallucinations- Despite their association with and inclusion in the definition of DTs (see below), hallucinations in and of themselves do not signify DTs. The distinction between withdrawal hallucinations and DTs is made by two aspects of presentation: timing and mentation. Withdrawal hallucinations with an otherwise normal sensorium occur early in the course, usually at 12-24 hours. Hallucinations of DTs is later in the game, typically 2-3 days out, and the patient is confused.
Seizures- these are usually isolated, or short spurts of tonic-clonic seizures from the ol’ GABA-glutamate imbalance. These seizures kinda have a rule of 6 to them: they occue 6-48 hrs after cessation, they must be 6 or fewer seizures, and they must be grouped within 6 hrs of the first seizure.5 Interestingly, these seizures are not uncommon and do not portend a rapid progression to DTs. If untreated though, 1/3 of patients will eventually go on to DTs.6 If the patient is in status or won’t stop going into and out of seizures, then think outside EtOH withdrawal seizures to the other badness that can accompany alcoholics (subdural, hypoglycemia, etc).
“Severe” withdrawal symptoms/Delirium Tremens (DTs) aka Alcohol Withdrawal Delirium
Lets be real. When we’re talkin’ severe withdrawal from alcohol, we’re talkin’ DTs. The better term for this is alcohol withdrawal delirium (AWD).
AWD is defined simply by two components: 1) alcohol withdrawal 2) delirium.
The DSM-V defined AWD this way: EtOH withdrawal as cessation/reduction of heavy/prolonged EtOH use and 2 of 8 symptoms (autonomic instability, hand tremor, insomnia, Nausea/vomiting, transient hallucinations, psychomotor agitation, anxiety, seizures).7 Delirium: disturbance in memory, awareness, attention that is a change from normal level for patient and fluctuates over course of day.7
Timing is also vitally important here as many of the symptoms involved in the diagnosis are also present earlier in the evolution of disease (ie hallucination and seizures). Delirium Tremens does not manifest until 2 to 3 days after alcohol cessation.8
We will skip the treatment of concurrent diseases as that was outlined above.
The treatment of the patient withdrawing from alcohol is going to depend on a few things: time from last drink, history of prior withdrawals and severity of symptoms.
The first two elements of this can be gathered from history. The severity of symptoms can be assessed generally, but calculation tools also exist. The most common is the CIWA score. This system scores from 0-67. While CIWA assists in determining severity of symptoms, many other factors come into play when deciding the modality and location of treatment. One must also consider: severity and chronicity of alcohol abuse, time since cessation, any concurrent use of other sedative-hyponotics, age, concurrent diseases, and history of prior withdrawals. All of the above have been show to increase the chance a patient goes into DTs.9
Low Risk History/Mild Symptoms (CIWA 0-8)
It is important to point out that many patients may not require active treatment. Patients without a heavy alcohol use history, who don’t have the red flags noted above, and have minimal symptoms (categorized quantitatively as a CIWA < 8) often require no medications.
Moderate Risk History/ Moderate Symptoms (CIWA 8-15)
This is the ambulatory treatment patient, if all the boxes are checked. Patients with moderate symptomatology and fall in the CIWA range of 8-15 can be considered for outpatient management if they: -Can take oral medications. -Have a reasonable level of self-care (aren’t psychotic, suicidal, cognitively impaired). -Have good social support for the withdrawal and treatment process. The ideal agent for treating withdrawal would be one that allows the GABA/glutamate imbalance in the brain to gradually return to normal without the hyper excitation. Comparisons of benzodiazepines to neuroleptic agents have shown neuroleptics to be inferior, with a RR of death at ~6.6 with these agents.8 The ideal benzo to use is a topic of debate. Unfortunately, attempted metanalyses on the topic have not shown one drug to rise to the top.8,10,11 Essentially, two schools of thought arise: 1) Use a long acting agent like Diazepam or Chlordiazepoxide which has a smooth, nature taper given its half life. Down side of these is they are metabolized by the liver 2) Use a short acting but “cleaner” agent like Lorazepam or Oxazepam, which do not have hepatic metabolism. Many opinions exist on this.12 How much to give is the next question. An approach I have liked and adopted is to tally the total ED dose required to cause symptomatic improvement/relief and create a taper in the following manner: 1) Day 1: Total ED dose of medication divided out four times a day. 2) Day 2: ¾ ED dose divided out four times a day 3) Day 3: ½ ED dose divided four times a day 4) Day 4: ¼ ED dose divided four times a day 5) Day 5: transition off While 4 days of therapy may not be a long enough treatment timeframe, by this period the patient should be in contact with an outpatient provider or detoxification center.4
Severe Risk History/ Severe Symptoms (CIWA >15)
This material could be its own podcast in and of itself. Luckily, alcohol withdrawal delirium (AWD, aka DTs) is relatively rare. It is estimated to be seen in ~5% of patients admitted for management of withdrawal.7 Mortality rates for AWD used to be as high as 15%, but with current treatment regimens numbers are closer to 1%.8
For treatment, benzos again are the agent of choice. Patients with AWD require aggressive and frequent dosing of a benzo, which leads to the recommendation of IV administration by most. The dose is unique to the individual and their tolerance, but the overall goal is the same— light sedation.
Again, there is no one benzo proven better than the others. Given that AWD often requires rapidly escalating dosing or drips, consideration of duration of action and active metabolites comes into play.
The agents with good pharmologic profiles include: Diazepam (Valium), Lorazepam (Ativan), Midazolam (Versed), and chlordiazepoxide (Librium, not IV!!). Generally, many prefer diazepam or other long acting agents with active metabolites because of the smoother transition and tapering. One should consider shorter acting agents and ones without hepatic metabolism (lorazepam) in patients with severe agitation or hemodynamic compromise requiring rapid escalation of dosing or in patients with cirrhosis. This helps prevent over-sedation down the road.
When do you know you’ve given enough? The answer isn’t in milligrams but in examination. Quietly sedated but rousable is the goal.8 To put this in a quantitative measurement, you want a RASS of -1.
Adjunctive agents may be needed to achieve this. The ones with the greatest amount of literate to support their use include phenobarb and propofol.1,5,7,8 Dosing of such agents will clearly be dependent on your amount of benzo given and patient dynamics. With dual sedative-hypnotic agents, preparation for airway control is a must.
1) What are the two neurotransmitters most disregulated in chronic alcoholics? What are they’re roles and how do they present in the withdrawal state?
2) Name 4 concurrent diseases to look for in the withdrawing alcoholic.
3) Do hallucinations and seizures mean DTs/AWD? Explain why or why not with a focus on timing.
4) What is the mainstay pharmacotherapy class for treating AWD? What scoring system can aid you in determining severity of withdrawal?
5) How do you prepare an outpatient medication regimen for the withdrawing patient? Who is fit for this treatment plan?
6) Outline your approach to the patient with AWD, when do you know you have reached your treatment goals? What is the patient’s disposition?
2) Management of drug and alcohol withdrawal. Kosten TR, O’Connor PG Engl J Med. 2003;348(18):1786.
3) Med Clin North Am. 1997 Jul;81(4):881-907. Pharmacotherapies for alcohol abuse. Withdrawal and treatment. Saitz R1, O’Malley SS.
4) Etherington JM. Emergency management of acute alcohol problems. Part 1: Uncomplicated withdrawal. Can Fam Physician. 1996 Nov;42:2186-90.
5) Etherington JM Emergency management of acute alcohol problems. Part 2: Alcohol-related seizures, delirium tremens, and toxic alcohol ingestion. Can Fam Physician. 1996 Dec;42:2423-31.
6) Victor M, Brausch C. The role of abstinence in the genesis of alcoholic epilepsy. Epilepsia. 1967;8(1):1.
7) Schuckit MA. Recognition and management of withdrawal delirium (delirium tremens). N Engl J Med. 2014 Nov 27;371(22):2109-13.
8) Mayo-Smith MF, Beecher LH, Fischer TL, Gorelick DA, Guillaume JL, Hill A, Jara G, Kasser C, Melbourne J; Working Group on the Management of Alcohol Withdrawal Delirium, Practice Guidelines Committee, American Society of Addiction Medicine. Management of alcohol withdrawal delirium. An evidence-based practice guideline. Arch Intern Med. 2004 Jul 12;164(13):1405-12.
9) Ferguson JA, Suelzer CJ, Eckert GJ, Zhou XH, Dittus RS. Risk factors for delirium tremens development. J Gen Intern Med. 1996;11(7):410.
10) Michael F. Mayo-Smith, MD, MPH. Pharmacological Management of Alcohol Withdrawal: A Meta-analysis and Evidence-Based Practice Guideline. JAMA. 1997;278(2):144-151.
11) Holbrook, Anne M., et al. “Meta-analysis of benzodiazepine use in the treatment of acute alcohol withdrawal.” Canadian Medical Association Journal 160.5 (1999): 649-655.
12) Bird RD, Makela EH. Alcohol withdrawal: what is the benzodiazepine of choice? Ann Pharmacother. 1994 Jan;28(1):67-71.
Core Content Show Notes & Questions
In this podcast we review a case of Ludwig’s Angina.
The objectives are as follows:
1) Introduce the physical findings of this often thought of but rarely seen diagnosis
2) Outline the associated anatomy
3) Create a treatment approach for the Ludwig’s patient
In order to diagnose this bad boy, you have to know the definition of the disease, which involves maxillofacial anatomy.
Ludwig’s has three important components:
1) Infection of the submandibular space (composed of the submylohyoid and sublingual spaces)
2) The infection is bilateral
3) The infection is aggressive and rapidly spreading
Don’t get lost in the terminology and all the potential spaces of the mouth. Remember K.I.S.S. (kept it simple, stupid)- Ludwig’s is a fast and mean floor of the mouth infection.
Mechanisms and Spread– “Its your stanky tooth”
Ludwig’s is most often from them chompers the patient hasn’t flossed, brushed, or noticed were rotting out of their face for years. Over 2/3 the time the infection is odontogenic, usually from the mandibular teeth. As a general principle, maxillary tooth infections tend to spread up and/or out, involving the infraorbital region or buccal area, whereas mandibular teeth will create infectious spread out or down.1
With all the fascial planes and potential spaces of the mouth, things can get confusing—We care about two spaces in Ludwigs: Sublingual and Submylohyoid. The scrawny little mylohyoid muscle separates these two potential spaces which actually communicate in the back of the mouth. The cellulitis of Ludwig’s tears right through this area, involving both spaces bilaterally.2
Once in the submandibular region, the cellulitis takes the potential space and fills it with infection. The tongue is displaced by this and can head out up or back—all of which are bad. Further communication can occur with the paraphyarngeal and then the retropharyngeal spaces. Epiglottitis, retropharngeal infections and even mediastinitis have been described.3-4 These complications are a talk for another day.
Manifestations– “Your double chin looks reeeeal angry”
It’s a gnarly infection- fevers, chills, and mouth pain are kind of a given. As the cellulitis takes potential spaces and makes them real, certain things have to get displaced:
Floor of the mouth– the submandibular face is swollen, exquisitely tender and has a classic “woody” feel to it, meaning it is taught and hard.2 If the patient didn’t have a double chin before, they will now.
Tongue– This is part of the life-threat and why we are scared of this disease. The tongue gets elevated and can occlude the airway. A slow suffocation from airway occlusion is the end outcome. In the pre-antibiotic era, this led to Ludwig’s having a near 50% mortality rate.5 Today numbers are cited in the single digits.3,6
Other clinical features of the disease basically stem from the above anatomic changes:
Muffled voice– Talking with your tongue pressed firmly against the roof of your mouth is no easy task
Drooling– Swallowing, too, can be a tall order with tongue mechanics so disrupted
Sniffing position- Just like our epiglottitis kids, when we want to maximize airway diameter as our throat starts to close, we may take a sniffing position.
Stridor– A step past the sniffing position (though not always a progression of symptoms), if you patient has stridor you better be prepping your ETT… and your scalpel.
Diagnosis– “Your mouth is being eaten, which is ironic”
The diagnosis of Ludwig’s is via the constellation of symptoms. While CT is the imaging modality of choice, never send a tenuous airway to CAT scan. As mentioned above, there are a few definitions that need to be met for it to be Ludwig’s:
a. Submandibular (submylohyoid + sublingual) infection
c. Aggressive and mean
Abscesses are typically not present in Ludwig’s given the rapidity of spread and early presentation of patients. However, in patients presenting later in the course (typically greater than 24-48 hours), abscesses can be present and do not preclude the diagnosis.6
As noted above, concurrent infection of the surrounding structures (epiglottis, parapharngyeal areas, etc) can occur.
Treatment– “A is for Asphyxia”
Airway Control– Its back them good ol’ ABCs. And with Ludwig’s it’s a hard stop at A. From an EM perspective, the cornerstone of treatment is airway protection. As noted, this is a hard livin’ fast movin’ infection, and any signs of airway compromise is a four alarm fire. Preparation for securing a difficult airway should commence. While prior recommendations were for awake surgical airway, advanced techniques including fiberoptic awake intubations have put this practice into anquity.7,10
Fight the Bugs– Antibiotics are the corner stone of management once the above is managed (ideally concurrently). It’s a mouth infection, so you are dealing with aerobes and anaerboes. This is not a time to skimp on antibiotic coverage. Activity against Bet-lactamase producing bacteria, MRSA, aerobes and anaerobes should be present.8 Combo penicillins like ampicillin-sulbactam or piperacillin-tazobactam are a great starting point.6,8 Clinda in your pen-allergic patients. Obviously, vanco or linezolid need to be added if MRSA is suspected and honestly, when is it not these days.
Source Control– Given most Ludwig’s stems from mandibular odontogenic infections, source teeth often have to be extracted.9 Abscesses, though uncommon and late in presentation, require I&D. While surgical flaying of the submandibular space to decompress the region was a common practice, it has fallen out of favor.11
Core Content Review Questions:
1) Define Ludwig’s angina.
2) Where does it usually originate from?
3) List the manifestations of Ludwig’s angina and those which are of concern.
4) How is this disease process diagnosed?
5) What is the treatment for ludwigs? Is there a role for surgery?
1) Fehrenbach MJ, Herring SW. Spread of Dental Infections. Practical Hygeine. 1997: 13-19
2) Srirompotong S, Art-Smart T. Ludwig’s angina: a clinical review. Eur Arch Otorhinolaryngol, 260 (2003), pp. 401–403
3) Furst IM, Ersil P, Caminiti M. A rare complication of tooth abscess–Ludwig’s angina and mediastinitis. J Can Dent Assoc 2001; 67:324.
4) Spread of Dental Infections. Fehrenbach MJ, Herring SW. Practical Hygeine. 1997: 13-19
5) Williams AC, Guralnick WC. The diagnosis and treatment of Ludwig’s angina: a report of twenty cases. N Engl J Med 1943;228:443–50
6) Reynolds SC, Chow AW. Life-threatening infections of the peripharyngeal and deep fascial spaces of the head and neck. Infect Dis Clin North Am 2007; 21:557.
7) Wolfe M, Davis J, Parks S. Is surgical airway necessary for airway management in deep neck infections and Ludwig angina? J Crit Care. 2011 Feb;26(1):11-4
8) Brook I. Microbiology and principles of antimicrobial therapy for head and neck infections. Infect Dis Clin North Am 2007; 21:355.
9) Emerg Med Clin North Am. 1985 Feb;3(1):161-78. Odontogenic infections. Rothwell BR.
10) Ovassapian, Andranik MD*; Tuncbilek, Meltem MD†; Weitzel, Erik K. MD‡; Joshi, Chandrashekhar W. MD† Airway Management in Adult Patients with Deep Neck Infections: A Case Series and Review of the Literature. Anesthesia & Analgesia: February 2005 – Volume 100 – Issue 2 – pp 585-589
11) Bross-Soriano D, Arrieta_Gómez JR, Prado-Calleros H, Schimelmitz-ldi J, Jorba-Basave S. Management of Ludwig’s angina with small neck incisions: 18 years experience. Otolaryngol Head Neck Surg 2004;130:712-7