Cardiac arrest, add antibiotics to the kitchen sink?

Clinical scenario:

You get a page out for a 55 yo M in cardiac arrest, EMS reports PEA on their arrival, patient has received 3 rounds of epi prior to arrival, patient achieves return of spontaneous circulation (ROSC) after 5 minutes of ACLS while in the ED. When family arrives they report the patient had been feeling unwell for several days and had a significant cough.  No obvious infiltrate was seen on initial chest xray.  The patient's BP is stable on an epi infusion. You admit the patient to the ICU. Your attending requests drawing blood cultures and starting the patient on broad spectrum antibiotics, and cites data stating antibiotics improves mortality in out of hospital cardiac arrest. You perform a brief literature review. 

Literature Review:

Out of hospital cardiac arrest (OHCA) has a very high mortality rate, where approximately only 23% make it to the hospital alive, and 7.6% survive to hospital discharge. (1) The most common etiology of out of hospital cardiac arrest is presumed to be myocardial in origin. However, several retrospective studies indicate that sepsis and bacteremia may also be a significant contributing factor to OHCA. A study by Coba et al in published in 2014 performed a prospective study to identify the incidence of bacteremia in OHCA patients. They enrolled 173 patients, where all patients had two sets of blood cultures drawn, 77 patients met exclusion criteria (trauma, pregnant, pediatric, single positive culture of skin flora). The overall incidence of bacteremia was 37% (65 patients). The most common bacterial species cultured were streptococcus and staphylococcus and Ecoli and klebsiella for gram positive and gram negative bacteria respectively. Bacteremic OHCA patient had significantly higher lactates, lower pH, and more frequent use of vasopressors. Notably the ED survival was significantly lower in the bacteremic patients (25%) compared to nonbacteremic patients (40%). However, 28 day mortality difference was insignificant in bacteremic vs nonbacteremic patients (93.8 vs 92.6%). The figure below by Coba et al lays out the proposed inter-relationships between bacteremia and sudden cardiac arrest. (1)

Proposed association between bacteremic infection and sudden cardiac arrest. From Coba et al.

Although there is very little data examining pre-existing bacteremia in OHCA, there has been a significant amount of research studying infection following ROSC in OHCA. The most commonly cited sources of post ROSC infection are lung possibly from aspiration during arrest, or gut likely from translocation of flora secondary to low flow state during arrest.  Davis et al performed a retrospective analysis on 138 patients admitted to the ICU following OHCA, and showed that 97.8% had at least one positive mark of infection within 72 hours (positive blood culture, consolidation on cxr, CRP greater than 100 or wbc greater than 11 or less than 4 x10^9 ). In this study approximately 38.4% of patients received antibiotics during the first 7 days of their ICU stay. The authors showed that mortality was significantly lower among those receiving antibiotics versus those not receiving antibiotics (56.6% versus 75.3%). However, highest mortality was within the first three days, and for patients who survived to day 3, there was no difference in mortality between those who received antibiotics already and those who had not. (2)

Take home points:

OHCA is typically presumed to be a primary myocardial event, however there is some data to suggest that sepsis is potentially a significantly under reported cause. Furthermore, there is also data to suggest that following ROSC, infection is quite common, and antibiotics may reduce early mortality. However, caution must be taken, as of yet there are no RTC's comparing prophylactic antibiotics versus placebo in OHCA.

Expert Commentary:
Dr. Holthaus one of our own critical care and sepsis guru's was nice enough to provide some of his own thoughts on this topic, and cardiac arrest in general. 

Things we'd like to see examined in future cardiac arrest RCTs:

1) Antibiotics during arrest - push dose, timing, coverage.

2) Propofol - control for this or exclude as a variable since it has been shown to cause some mitochondrial dysfunction and may be thwarting potential resuscitation benefits.

3) Epi dosing - frequency, continue 1mg push dose vs lower dose vs maximum that is less likely to cause or further exacerbate either ischemic or post-inflammatory cardiomyopathy.

4) Vasopressin-Steroid-Epi- for ED arrest. Link to VSE study in JAMA . VSE (vasopresson-steroids-epi) better than Epi alone for in-hospital arrest Vasopressin (20u, q 3-5min, max 100u, w 1 mg epi pushes)-Methypred (40mg IV x1) w better ROSC (84% vs 66%) and better CPC1/2 survival (14% vs 5%).  Major caveat is time to ACLS was very low at 2 min for both which is way faster than many we see in the ED that are frequently >10 min downtime before EMS.  Hypothesis generating, re-hinting at potential beneficial role of vasopressin and steroids for shock (like sepsis). 

5) ED ECMO for cardiac arrest or refractory/severe shock

6) Remote ischemic conditioning immediately after ROSC- 5 min thigh BP tourniquet to >20mmHg above SBP then deflate, repeat 3-4 times, reportedly induces systemic circulation of a protein that blocks CNS/cardiac opening of the "mitochondrial permeability transition pore" which is the final common pathway for ischemic reperfusion injury).  On recent ED ECMO podcast (Shiner-Bellezo) Link to podcast Remote ischemic conditioning 

Personally since everything (ACLS) isn't getting much results, if I can remember to I will do Vasopressin-Methypred-Epi dosing, I am less excited about a lot of epi (ie 3 pushes tells me if they're trending toward making it or not), I've pushed zosyn and then hung vancomycin in a code (after learning about Coba study). I have generally avoided propofol in past because of known myocardial suppression, and now with concern for mitochondrial insult, I just use fentanyl/versed. In addition I  will try thigh remote ischemic reconditioning, and continue targeted temperature management to 33-36C while hoping for ED ECMO (which I think will be the biggest game changer)  

Submitted and Edited by Louis Jamtgaard PGY-3 @Lgaard
Faculty Review by Chris Holthaus

References

 1) Coba V et al. The incidence and significance of bacteremia in out of hospital cardiac arrest.

Resuscitation. 2014 Feb;85(2):196-202. d

2)Davies K et al. Early antibiotics improve survival following out-of hospital cardiac arrest.Resuscitation 2013 May; 84 (5) : 616-9.

Subchorionic Hematoma: incidental finding or early risk?

Clinical Scenario:

A 20 yo G1P0 at 6wk1day by LMP presented with vaginal bleeding.  She had onset of bleeding 1 hour prior to arrival, soaked through 1 pad.  She was seen at her OB earlier that day (prior to onset of bleeding) and had an US which showed +FHR.  Transabdominal and transvaginal ultrasound showed an IUP with +FHR of 120 BPM (image below).  Her beta hCG was 72,813 and she was Rh+.  Hypoechoic material was seen surrounding the gestational sac, consistent with subchorionic bleeding.  The patient was given return precautions and instructed to follow-up with her OB in 48 hours.  You wonder if should have given any specific precautions regarding subchorionic hematoma?

Correcting Acidosis or Just adding CO2?: On Sodium Bicarbonate for Metabolic Acidosis

Clinical Scenario:

You are working in the emergency department when an elderly male is brought in by EMS after being found unresponsive at home with an unknown downtime.  The paramedics report a possible seizure.  His finger stick glucose registers as critical high.  Post-intubation for poor GCS,  his initial labs reveal an ABG of  6.8/20/90 and a lactate of 18.   As you are signing out the patient to the ICU,  the ICU team requests a sodium bicarbonate infusion.  You wonder, will sodium bicarbonate administration improve outcomes or correct acidosis faster when compared to normal saline?

Physiology & Literature Review:
Other than well-defined indications for sodium bicarbonate administration (such as treatment of Na-channel blockade in TCA overdose or to induce alkalinization in salicylate toxicity), one should be skeptical about administering sodium bicarbonate simply for acidosis. On the one hand if a patient is acidotic, it makes intuitive sense that you should try to alkalinize them, which is why sodium bicarbonate has been used so often in the past.  On the other hand, there is evidence to show that administration of sodium bicarbonate shifts the oxygen dissociation curve, increasing hemoglobin affinity to oxygen,  and resulting in paradoxical tissue hypoxia and causes an increase in lactate production. In addition, it causes an intracellular acidosis.  Despite this,  because it tends to be part of the "code cocktail",  it is often administered anyway. 

Rise in EtC02 after bicarb (Dr. Sacchetti video)

The effect of administration of Sodium bicarbonate on the end-tidal CO2 in an intubated patient with severe metabolic acidosis is well demonstrated by  this video by Dr. Alfred Sacchetti. While we disagree in giving a bicarb drip as mentioned in the video, it does demonstrate the acid-base physiology in real time. 

A small randomized-controlled trial published in Critical Care Medicine more than 20 years ago gave either a blinded bolus of saline or sodium bicarbonate to patients with lactic acidosis vasopressor support [1].  They then checked ABGs one hour later.   While sodium bicarbonate did increase the venous bicarb level, improved pH, it did not improve hemodynamics.

Thomboembolic events after cardioversion in afib

Clinical Scenario:
55 year old with past medical history of hypertension presents with sudden onset palpitations and chest pain that awoke him from sleep at midnight.  Patient presents 3 hours later with complaint of palpitations, chest pain, shortness of breath with stable vitals.  EKG demonstrates atrial fibrillation (a.fib).  Patient undergoes successful synchronized cardioversion.

Clinical Question:
In a patient who is electrically cardioverted within 48 hours of symptom onset of new atrial fibrillation, what is the incidence of thromboembolic complications?  Do you still have to anticoagulate?

Literature review:
Based on the Finnish CardioVersion Study, which included 2,481 patients who had a.fib for less than 48 hours and underwent cardioversion and were NOT started on oral anticoagulation nor peri-procedural heparin, there are certain groups who have higher risks for thromboembolic events.  Of the group as a whole, 0.7% (95% CI 0.5-1.0) had thromboembolic events within 30 days with a median of 2 days and mean of 4.6 days.  The three highest risk factors were female gender (OR 2.1 95% CI 1.1 to 4.0), heart failure (OR 2.9 95% CI 1.1 to 7.2), and diabetes (OR 2.3 with 95% CI 1.1 to 4.9).  Those with no heart failure who were younger than 60 years old had the lowest risk of thromboembolism (0.2%). 

Example of Afib

Hitting the bottle hard, beyond benzos for AWS.

Clinical Scenario:

It’s the age old story, chronic alcoholic evaluated for an unrelated issue, cleared from that issue only to now have developed alcohol withdrawal. The patient in question is a middle aged male with heavy alcohol use history who was transferred from another center for specialist evaluation. After being cleared by the consultant, he is now 24 hours from his last drink and looks decidedly not well. He is tremulous, tachycardic, anxious, and vomiting. You recognize his alcohol withdrawal, but despite treatment, he rapidly worsens requiring very high doses of benzodiazepines and an ICU admission. What adjunct therapies are available for severe alcohol withdrawal?

Synapse in AWS (© 2015 Cynthia Turner cynthiaturner.com)

Alcohol abuse is an exceedingly common problem and alcohol-related ED visits are encountered daily across the country.  Annually, around 500,000 episodes of acute alcohol withdrawal require treatment. The symptoms typically begin to manifest within hours to days after cessation of alcohol and typically peak at 2 – 3 days.  The clinical course of alcohol withdrawal varies widely among patients.  Chronic alcohol use leads to down-regulation of GABA receptors and up-regulation of NMDA glutamate receptors. Additionally, GABA receptor expression is suppressed. In the active drinker, this allows patients to maintain a normal level of consciousness despite blood alcohol levels that would incapacitate a nondrinker. Withdrawal is therefore, associated with a decrease in GABAergic activity and an increase in glutaminergic activity. The increase in excitatory activity and loss of inhibitory activity results in the symptom complex of alcohol withdrawal. Symptoms include autonomic hyperactivity, tremor, insomnia, nausea/vomiting, hallucinations (commonly visual or tactile in addition to auditory), psychomotor agitation, anxiety, generalized tonic-clonic seizures. Benzodiazepines are the standard of care for alcohol withdrawal. Adjunct therapies of old have targeted adrenergic symptoms, not so much the underlying disease. These include beta-blockers and calcium channel blockers. Other more targeted therapies like gabapentin are hindered by prolonged onset of action. Adjuncts that make a bit more sense pharmacologically and are gaining popularity include barbiturates, ketamine, and dexmedotomidine.  Let’s look at some of that data.

EKG Challenge #8 Case Conclusion - The Way to the Heart is through the BRAIN

A middle-aged female is brought in by EMS yelling and thrashing on a stretcher.  Per report, she was found unresponsive next to the couch by her daughter.  She was given 2mg of IM Narcan and woke up a bit and has been agitated ever since.  You just begin your assessment and order some labs before you are pulled away to two Level I traumas and an impending respiratory arrest.  As you head back to the patient's room to complete your assessment, you receive a "critical value" phone call from the chemistry lab.  You are told that your patient has a troponin of 0.65.

After thinking to yourself, "Oh S--- I didn't expect that, not even 100% sure why I ordered it", you realize that you have not yet seen the EKG.  It's not in the chart, so you hurry to her room to find a nurse and security wrestling with  half-naked agitated patient who is trying to stand up on the stretcher and grab on to the light fixture above.  You call your attending and he agrees "that THIS" (turning to the wrestling match) "is not going to work."  You decide to intubate her to facilitate your greatly expanded workup for altered mental status.  Post intubation, you get this EKG:

When you first look at the EKG nothing in particular really jumps out at you.   There are some T wave inversions in I and avL,  as well as a biphasic T wave in V2. Sure that there is something more, you decide to take a moment and go through it systematically.  When you get to examining the intervals, everything on the surface looks fine, but you remember reading on Steve Smith's ECG blog that calculating the QT interval can be tricky (especially for computers) and decide to calculate it yourself:

To calculate the QT interval, you start by drawing a line along the maximum slope of the T wave  and marking where it intersects the isoelectric line.  The distance from the preceding Q wave to this intersection point is the  QT interval :

To calculate the corrected QT (QTc), you  use Barrett's formula and divide the QT interval in milliseconds by the square-root of the preceding RR interval (in seconds).   In the case of our patient, the QTc is 525 ms, prolonged by any standard.

While you are running through your differential for altered mental status + positive troponin + prolonged QT, the patient is taken get a head  CT.  You go with her and recognize the subarachnoid hemorrhage star of death as it appears on the screen of the CT tech in front of you:

Neurosurgery emergently places a ventriculostomy drain and the patient is admitted to the Neuro ICU.   When you go home after your shift, your brain is buzzing, making sleep impossible.  You've heard the term "neurocardiogenic" injury before and decide to look into this interesting brain-heart connection.

Neurocardiogenic injury is a term used to describe the diverse number of cardiac abnormalities associated with central nervous system disease[1].  Patients with neurovascular emergencies (most notably SAH) can develop subendocardial myocyte damage, global or regional left ventricular systolic dysfunction (incidence of 10-28% in SAH), low-grade troponin elevation (20-40% of patients with SAH), and a diverse number of EKG abnormalities linked to the development of life-threatening cardiac arrythmmias.  Significantly, these occur even in the absence of underlying cardiac disease.  Multiple theories have been proposed for the mechanism of neurocardiogenic injury, the most popular of which postulates that a "catecholamine-surge" leads to myocardial damage.  Others postulate that a wide-spread inflammatory state, such as seen in septic shock -induced myocardial dysfunction, is responsible.  Interestingly, the degree of cardiac injury as measured by troponin level (>0.3 ng/mL) correlates with SAH severity (in terms of Hunt/Hess grading) [2].

With respect to EKG findings specifically, EKG abnormalities are common in the acute phase of neurovascular disorders.  They occur in 60-70% of patients in ICH, 40-70% of patients with SAH, and 15-40% of patients with ischemic stroke [1].  The most common EKG abnormality is QT prolongation, as seen in our patient. QT prolongation may precede sudden death from ventricular arrythmmias among patients with SAH [3].  Other EKG abnormalities in acute stroke include -

1.  Wide, deep and bizarre appearing T wave inversions - The most striking EKG manifestation of CNS disorders are bizarre-appearing, deep and widely splayed T waves usually in the precordial leads [4,6].  Some form of T wave abnormality, including both flattening and inversions, is seen in approximately 15% patients with ischemic stroke and 55% of patients with SAH [1]. While we typically associate T wave inversions with acute myocardial ischemia, the EKG changes can occur even patients with normal coronaries [5].

 EKG from patient with an acute L PCA ischemic stroke. Note marked QT prolongation and bizarre-appearing T wave inversions in V2-V5

2.  U waves - In the original case series by Burch (1954) describing EKG abnormalities in stroke, it was observed that a subset of tracings had U waves even in the absence of hypokalemia [4].  Subsequent studies have found new U waves in 13% - 15% of patients with acute ischemic stroke and SAH [1].  In a subset of these cases, it is possible that some of the prolonged QT observed is actually a form of T-U fusion.

Figure from 4 from Burch (1954) demonstrating U waves in a patient with intracerebral hemorrhage

3.  ST elevation - Some form of ST segment change occurs in approximately 20-30% of patients with stroke.  A small subset of these patients will also have ST elevation (see example below).  While ST elevation can be seen with neurocardiogenic injury, it is still important to consider dissection in patients with cerebral ischemia and ST elevation on their EKG.

EKG from 76 yo male with SAH who subsequently underwent cardiac cath with clean coronaries (Source: Reference 6)

While the EKG changes are interesting,  do they have any clinical significance or prognostic value?  This remains unclear.  Cardiac dysfunction and EKG abnormalities due to neurocardiogenic injury are usually transient, normalizing over days 3-8 post-injury (at least for SAH)[1].  One small retrospective study of only 58 patients attempted to examine whether EKG status was predictive of all cause mortality in SAH [7].  While it was found to correlate strongly with severity of SAH, no independent predictive value was found (see table below).  The EKG, therefore, in addition to the clinical exam, may be an indirect marker of SAH severity associated with increased all-cause mortality.

For the most part, the EKG changes themselves do not require specific treatment, but clinical investigation should include evaluating for other potential causes (i.e. electrolyte abnormalities or true coronary ischemia).  Patients with these changes should have continuous cardiovascular monitoring during the acute period because of the risk of serious arrythmmia.  Despite risk of arrythmmia, these patients benefit from specialized neurocritical care, and belong in a NeuroICU instead of a cardiac care unit.

Submitted by Maia Dorsett (@maiadorsett), PGY-3
Faculty reviewed by Peter Panagos and Douglas Char

Take home points:  Troponin elevation + EKG changes does not automatically point to primary cardiac pathology and can occur even in the absence of underlying cardiac disease.  Remember to consider central nervous system pathology in a patient with altered mental status + EKG changes or elevated troponin.  Because EKG changes can have important clinical effects (such as predisposition to life-threatening arrythmmias), the EKG is an important component of the clinical work-up for CNS disorders. And as always, drug-induced altered mental status should be a diagnosis of exclusion because sometimes people use heroin to treat the worst headache of their life.

References:
1. Kopelnik, A., & Zaroff, J. G. (2006). Neurocardiogenic injury in neurovascular disorders. Critical care clinics, 22(4), 733-752.
2. Hravnak, M., Frangiskakis, J. M., Crago, E. A., Chang, Y., Tanabe, M., Gorcsan, J., & Horowitz, M. B. (2009). Elevated cardiac troponin I and relationship to persistence of electrocardiographic and echocardiographic abnormalities after aneurysmal subarachnoid hemorrhage. Stroke, 40(11), 3478-3484.
3.Oppenheimer, S. M., Cechetto, D. F., & Hachinski, V. C. (1990). Cerebrogenic cardiac arrhythmias: cerebral electrocardiographic influences and their role in sudden death. Archives of Neurology, 47(5), 513-519.
4.Burch, G. E., Meyers, R., & Abildskov, J. A. (1954). A new electrocardiographic pattern observed in cerebrovascular accidents. Circulation, 9(5), 719-723.
5.Cropp, G. J., & Manning, G. W. (1960). Electrocardiographic changes simulating myocardial ischemia and infarction associated with spontaneous intracranial hemorrhage. Circulation, 22(1), 25-38.
6. Catanzaro, J. N., Meraj, P. M., Zheng, S., Bloom, G., Roethel, M., & Makaryus, A. N. (2008). Electrocardiographic T-wave changes underlying acute cardiac and cerebral events. The American journal of emergency medicine, 26(6), 716-720.
7. Zaroff, J. G., Rordorf, G. A., Newell, J. B., Ogilvy, C. S., & Levinson, J. R. (1999). Cardiac outcome in patients with subarachnoid hemorrhage and electrocardiographic abnormalities. Neurosurgery, 44(1), 34-39.

Droperidol the psycho dropper or heart stopper?

Clinical Scenario:
You are working a typical EM-1 shift loaded full of psychiatric patients, EMS brings you another agitated male with a history of schizophrenia. He is shouting absurdities and threatening staff members.  The RN glances over at you, 5/2 doc? You're feeling a little different today and order 10mg of droperidol IM. The drug is administered and the patient calms down. With pride you present the patient to your attending. Your attending is alarmed and immediately requests an EKG and places the patient on a cardiac monitor and tells you the patient is in imminent danger of converting into torsades de pointes (TdP) secondary to prolonged QT.  You perform a rapid review of the literature.