UMEM Educational Pearls

Title: Electrocardiographic Changes at the Early Stage of Status Epilepticus: First Insights From the ICTAL Registry.

As the song goes: “the thigh bone is connected to the hip bone, the hip bone is connected to the back bone.” It turns out that the brain electrical activities are also connected to the heart conduction activities.

In a multi-center (23 French ICUs) retrospective analysis of 155 critically ill patients with status epilepticus, ECGs were done within 24 hours of onset of status epilepticus, and were independently reviewed by cardiologists showed abnormalities in 145 (93.5%) of patients.

Below is a list of events that occurred more than 10% of events.

Abnormal rate (<60 or > 100 beats/min         64 (44%)

Negative T-waves                                           61 (42%)

Flattened T-waves                                           18 (12%)

ST elevation                                                    24 (16.6%)

ST depression                                                 26 (17.9%)

Left axis deviation                                          22 (15.9%)

Discussion:

Major ECG abnormalities were not associated with 90-day functional outcome in multivariable logistic regression.

The brain-heart axis could be affected by antiseizure medication. For example, phenytoin, lacosamide are sodium channel blockers while benzodiazepines, propofol, barbiturates with their GABAnergic effects will also display cardiac side effects.  This current study was not able to tease out whether the cardiac effects were from medication. Therefore, further studies are needed to figure out the cardiac effect for patients with status epilepticus.

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Applying a cervical collar to all patients involved in motor vehicle collisions and mechanical falls has been shown to add to patient discomfort, unwarranted imaging studies and prolonged on scene time for emergency medical services. This study adds further evidence that paramedics can use validated algorithms to clinically clear cervical spine injuries without any bad outcomes including spinal cord injuries. EMS medical directors and all of us who interact with EMS providers should be proactive in developing protocols to use cervical immobilization in appropriately selected patients only.  This study used the Modified Canadian C-Spine Rule. 

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Non-dihydropyridine calcium channel blockers, verapamil and diltiazem, can induce hypotension when administered intravenously (IV) in approximately 4% of patients.  It has previously been taught that administering IV calcium before administering these medications may prevent the hypotension.  Previously, this theory was tested for verapamil and found success with reducing hypotension.  Only one study has been done exclusively with diltiazem and it found no benefit. 

In a new multicenter retrospective cohort study of adults in the ED, patients were randomized into two groups: those who received diltiazem alone and those who received calcium with diltiazem for atrial fibrillation/atrial flutter (AF/AFL) with a HR ≥ 120 bpm. Patients were excluded if they required electrocardioversion, had other agents prior to diltiazem, incomplete information, were pregnant or incarcerated. The primary outcome was change in SBP 60 minutes (+/-30 minutes) after diltiazem administration.

Baseline characteristics: 73 year old, equal male:female, predominantly white patients.  40% had new onset AF/AFL and the initial HR was 140 in both groups. There were 198 patients in the diltiazem group and 56 patients in the combination group.  Notably, patients in the combination group had a lower presenting SBP 109 (101-121) vs 123 (114-132) P<0.0001 which matches classical teaching for when to consider calcium use. Additionally, patients in the combination group received a lower diltiazem dose of 10mg vs 15mg in the monotherapy group p=0.004 with both group receiving doses lower than the standard 0.25 mg/kg dosing recommendation.

Outcomes:

• Median change in SBP was not different between the monotherapy and combination therapy groups: (-2 mmHg vs -1.5 mmHg, p= 0.642)
• There was no difference in:
  • Time to rate control (1.4 vs 1.8 hours, p= 0.141)
  • Time to sustained rate control (7.9 vs 7.7 hours, p=0.570)
  • Change in HR at 60 minutes: (-33 vs -34 bpm, p=0.428)
• A subgroup analysis looking at timing of calcium (i.e. before or with diltiazem administration) also found no difference.

Take Home Point:

Administration of IV calcium may not be as beneficial as previously thought to prevent hypotension induced by diltiazem administration.  This particular study is confounded by the relatively low doses of diltiazem overall, but utilizing a lower dosing strategy in patients with low SBP is a reasonable safety strategy.

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Background: 

There have been a few studies that suggested that there may be some neuroprotective effect with a higher MAP goal in post-arrest patients. However, these studies were small and/or observational. 

Intervention:

-The BOX trial was a double-blind, dual-center (Denmark), randomized trial 

-Study population: >18 yo, OHCA of presumed cardiac cause

-Pts randomized to higher (77 mmHg) vs. lower (63 mmHg) MAP goal

-double-blinded by attaching a module that reported a BP that was 10% higher or lower than the pt’s actual BP

-Notable exclusion criteria:

-unwitnessed asystole or suspected intracranial bleeding/stroke

Results/Primary outcome:

-No sig difference in composite of death + Cerebral Performance Category of 3 or 4  (3= severe disability, 4= coma) within 90 days

-133 patients (34%) in the high-target group vs 127 patients (32%) in the low-target group (hazard ratio, 1.08;95%CI, 0.84 to 1.37; P=0.56)

Caveats/Takeaways:

-Mean difference in BP was 10.7 mmHg (95[CI], 10.0 to 11.4) which is still relatively clinically significant, but was lower than their goal difference of 14 mmHg

-They used IVF to target a CVP of 10 mmHg prior to initiation of norepi and used dopamine "if necessary"

-Consider generalizability given study population was patients with presumed cardiac cause of arrest

-Keeping a lower MAP goal of >65 mmHg is reasonable in post-arrest patients

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In a small study at a single level one trauma center, ? of patients screened positive for illicit fentanyl use prior to violent or intentional injury. Those who screened positive were more likely to require ICU admission and had a higher rate of previous trauma center admission. The authors concluded: 

“Exposure to illicit fentanyl was common among victims of violence in this single-center study. These patients are at increased risk of being admitted to intensive care units and repeated trauma center visits, suggesting fentanyl testing may help identify those who could benefit from violence prevention and substance abuse treatment.”

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Question

21-year-old college softball player presents for evaluation of Left hand/wrist pain following batting practice.

She states her pinky is “tingly”

On exam, there is tenderness over her volar ulnar wrist.

You obtain an X-ray.

https://prod-images-static.radiopaedia.org/images/52314027/a662d8f338ec08ba56178463638d25_jumbo.jpeg

What’s the diagnosis?

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Given my previous post on APRV (11/6/2022) and while I take issue with many of the author's statements, I wanted to share a very well referenced article with an excellent discussion on the current gaps in the knowledge around APRV and its use.

One statement I do agree with is the need for a well-designed and adequately powered trial of this mode in an admittedly difficult-to-study population.

Fortunately, this article has an invited rebuttal pending from Dr. Habashi which I am sure will appear in the Educational Pearls in short order. 

Good luck to the residents on the ITE!

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This study looked at 69,321 head injured patients over age 65 in a health care database for delayed intracranial hemorrhage (within 90 days of visit). 58,233 patients were not on oral anticoagulants, 3081 (4.4%) were on warfarin and 8007 (11.6%) were on direct oral anticoagulants. One percent of patients not on anticoagulation and those on oral direct anticoagulation had a delayed hemorrhage while those on warfarin had a 1.8% delayed hemorrhage rate.

Bottom Line: Direct oral anticoagulants do not increase the risk of delayed intracranial hemorrhage in patients over age 65 from baseline but warfarin does. 

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Sympathetic Crashing Acute Pulmonary Edema (SCAPE) (also known as flash pulmonary edema) is an extreme form of hypertensive acute heart failure where a surge of high blood pressure from catecholamine surge and sudden vascular redistribution causes sudden onset decompensated heart failure hallmarked by rapid pulmonary edema and symptoms of hypoxia and dyspnea.

This is treated by systolic blood pressure control and venous vasodilation with IV nitroglycerine, bilevel positive airway pressure (BPAP), and diuretics if needed. A common error in treatment is administration of the traditional IV nitroglycerine infusion dosing protocol in which the nitroglycerine infusion is started at 5 mcg/min and slowly increased by 5 mcg/min increments until the clinical response is seen. However, in this syndrome, rapid blood pressure control and correction of vascular redistribution is critically important to reverse the central factor for patient decompensation. Lack of blood pressure control places the patient at risk of further cardiac decompensation or respiratory failure ultimately requiring intubation.

Increasing literature has been published on the concept of high dose or push dose IV nitroglycerine for the treatment of this syndrome. Many of these studies show decreased rates of intubation, decreased ICU admissions, and shorter hospital length of stays with high dose or push dose nitroglycerine, while also demonstrating low risk of hypotension.

The actual dose of the high-dose nitroglycerine administered in these trials is variable, with some trials administering nitroglycerine 1-2 mg IV pushes every 3-5 minutes, and other trials using a nitroglycerine infusion at a much higher starting rate (between 200-400 mcg/min) with rapid down-titration as blood pressure is controlled.

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In December 2022, The American College of Surgeons released a practice guidine discussing screening trauma patients for mental health disorders and substance use disorders. There is a very high likelihood that your acute trauma patient has a pre-existing disorder.

"Over 50% of hospitalized trauma patients report an alcohol and/or drug use diagnosis during their lifetime. At the time of admission, one in four trauma victims meet diagnostic criteria for an active alcohol use problem and 18% meet diagnostic criteria for a drug use problem".

Screening, Brief Intervention and Referal to Treatment (SBIRT) programs have a major impact on injury recidivism and future mortality. Trauma patients should be screened for mental health disorders and substance use disorders. 

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Question

Background: The use of sodium bicarbonate in the treatment of out-of-hospital cardiac arrest (OHCA) has been longstanding despite conflicting data regarding its benefit, outside of clear indications such as toxic ingestion or hyperkalemic arrest.

Study: A recent retrospective cross-sectional study by Niederberger et al.¹ examined prehospital EHR data for ALS units responding to nonpregnant adults with nontraumatic OHCA, noting use of prehospital bicarb and the outcomes of 1) ROSC in the prehospital encounter and 2) survival to hospital discharge. They created propensity-matched pairs of bicarb and control patients, with a priori confounders: age, sex, race, witnessed status, bystander CPR, prearrival instructions, any defibrillation attempt, use of CPR feedback devices, any attempted ventilation, length of resuscitation, number of epi doses.

There were 23,567 arrests (67.4% asystole, 16.6% PEA, 15.1% VT/VF), 28.3% overall received sodium bicarb. 

Results: 

In the propensity-matched sample, survival was higher in bicarb group (5.3% vs. 4.3%; p=0.019).

• Asystole (bicarb 3.3 vs 2.4%; p = 0.020)
• PEA (bicarb 8.1% vs 5.4%; p=0.034)

There were no differences in rate of ROSC overall, but looking at the different rhythms, ROSC was higher in the bicarb group with asystole as the presenting rhythm (bicarb 10.6 vs 8.8%; p=0.013) but not PEA or VT/VF.

*There is no indication by the authors as to the dosing of bicarb most associated with survival to hospital discharge (or ROSC in asystole) in the study, however a previous study has indicated that a single amp of bicarb is unlikely to significantly improve severe metabolic acidosis (pH <7.1),² so the general recommendation of at least 1-2mEq/kg should be employed.

Bottom Line: The use of sodium bicarb may increase survival in OHCA with initial PEA/asystole. The recommended initial dose is 1-2mEq/kg; giving at least 2 amps of bicarb (rather than the standard 1) should achieve this in many patients.

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Question

The classic teaching regarding penetrating neck trauma is violation of the platysma muscle in zones 1 and 3 requires angiography, endoscopy and bronchoscopy.  Injury to zone 2 is an automatic operative evaluation. Now, more anatomic and physiologic signs dictate operative management and those not meeting these hard signs get evaluated with Ct angiography. 

Neck zones and hard vs soft signs available by clicking link

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ACE-inhibitor (ACEi) induced angioedema is mediated by bradykinin and there are no proven medications for the treatment of this disease. Theoretically, a C1-esterase inhibitor (C1INH) could be beneficial; however, data has not demonstrated any efficacy for these agents.  

Strassen et al. recently published a double-blind, randomized, controlled, multicenter trial of 30 patients comparing C1NH (Brand Name: Berinert) to placebo. In addition to standard treatment, a dose of C1INH (Berinert) 20 IU/kg or placebo (0.95% NaCl) was administered intravenously.

The primary endpoint was the time to complete resolution of signs and symptoms of edema (TCER). When compared to placebo, the original primary analysis demonstrated that the placebo arm (15 hours) resolved faster than the C1INH arm (24 hours, p=0.046).

This study is further evidence against the use of C1INH for ACE-inhibitor induced angioedema. The primary focus in the treatment of ACEi induced angioedema should continue to be airway management.

For reference, at our institution we have both C1INH (Berinert) and icatibant on formulary and they are restricted to only being used for acute hereditary angioedema attacks and cannot be used for ACEi induced angioedema.

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Otitis media is a common pediatric complaint seen in the primary care, urgent care, and ED settings. Recommendations for timing of treatment and deferral of treatment have emerged over the last several years, as have recommendations for regimens for recurrent infections in the age of resistant organisms.

When to consider observation over antibiotics:

• If symptoms <48 hours, no severe pain, and fever < 39C and child is 2 years or older (either unilateral or bilateral AOM) OR unilateral AOM with symptoms <48 hours, no severe pain, and fever < 39C and child is 6 months to 2 years
• If observing, consider either a prescription that parents can fill if symptoms persist or ensure prompt primary care follow up

Initial treatment

High dose amoxicillin (90 mg/kg/day divided BID)

• If true penicillin allergy, can use cefdinir or cefpodoxime if tolerated or trimethoprim-sulfamethoxazole or a macrolide (e.g. azithromycin) but rates of resistance are higher
• Cefdinir and azithromycin are the most commonly used  
• Levofloxacin is also an option for age >8 years

Recurrent Otitis Media

If less than 30 days from initial treatment, presumed to be persistent

• If previously on amoxicillin, start amoxicillin-clavulanate (extra strength suspension has highest amoxicillin to clavulanate ratio and should be used)
• If previously on amoxicillin-clavulanate, ceftriaxone either for 3 days or 2 doses 36 hours apart

If greater than 30 days from initial treatment can treat as new episode (so amoxicillin unless previous documented resistant infections)

Duration of Antibiotics

• Less than 2 years, 10 days
• 2 years and up, 5-7 days

Other Considerations

• Amoxicillin-clavulanate should be used as an initial agent if there is concurrent purulent conjunctivitis
• Children with tympanostomy tubes and purulent otorrhea may be treated with otic fluoroquinolones (with or without dexamethasone), as long as debris does not obstruct entry of antibiotic drops
• Remember that the otic canal and TM can become red with fever and non-purulent effusion is common with URI
• Remember to treat pain and fever!

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When managing a hypotensive patient who may have some element of cardiogenic shock, it has long been debated whether it is better to start an inodilator like dobutamine, and use a true vasopressor like norepinephrine to offset the vasodilation, or start an inopressor like epinephrine.  Currently, this is largely a practice pattern issue, with different providers and specialties tending to make different choices (in my anecdotal experience, medical intensivists tend to do norepi+dobutamine, whereas cardiac surgeons and intensivists tend to use epi).  

Banothu et al recently studied this question in children with "cold" septic shock (they do not specify how this was defined) and found quicker time to resolution of shock with norepi+dobutamine vs epinephrine.  It should be noted that this was a secondary outcome, was a small study, was in children (who I'm told are not just little adults), and no difference in mortality or patient oriented outcomes was found.  However, this is a good opportunity to review what is known on this topic:

-A small RCT in Lancet 2007 by Annane et al found no difference

-A very small RCT in Acta Pharmacologica Sinica 2002 by Zhou et al suggested norepi-dobutamine has favorable effects on gastric mucosa and tissue oxygenation relative to epi or dopamine

-A small RCT in Intensive Care Medicine 1997 similarly suggested that oxygenation in the splanchnic circulation may be better with norepi+dobut than epi.

Take Home: There is very limited evidence in either direction when choosing between an inodilator + vasopressor (e.g. norepi + dobutamine) vs single inopressor (e.g. epi) strategy for a hypotensive patient in which inotropy is desired.  There is some weak evidence that norepi + dobutamine may be better for maintaing gut oxygenation and may resolve shock faster.  Personally, I would weakly recommend norepi + dobutamine over epinephrine, but continuing to follow provider preference and go with the agent(s) you're most comfortable with is also very reasonable.  If using the inodilator/vasopressor combination, it is recommended to titrate the vasopressor (e.g. norepi) to MAP and inodilator (e.g. dobutamine) to a measure of cardiac function such as CO/CI.  

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Missing blunt cervical vascular injuries can lead to delayed catastrophic sequela such as stroke. Usie the epanded Denver criteria to help you identify these injuries.

Expanded Denver criteria for BCVI

-Signs/symptoms of BCVI

Potential arterial hemorrhage from neck/nose/mouth
Cervical bruit in patient less than 50 years old
Expanding cervical hematoma
Focal neurologic defect: TIA, hemiparesis, vertebrobasilar symptoms, Horner's syndrome
Neurologic deficit inconsistent with head CT
Stroke on CT or MRI

-Risk factors for BCVI

High-energy transfer mechanism
Displaced midface fracture (LeFort II or III)
Mandible fracture
Complex skull fracture/basilar skull fracture/occipital condyle fracture
Severe TBI with GCS less than 6
Cervical spine fracture, subluxation, or ligamentous injury at any level
Near hanging with anoxic brain injury
Clothesline type injury or seat belt abrasion with significant swelling, pain, or altered mental status
TBI with thoracic injuries
Scalp degloving
Thoracic vascular injuries
Blunt cardiac rupture
Upper rib fractures

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In a recent study in The Lancet, researchers at NIH attempted to test the hypothesis that optimal hydration may slow down the aging process. 

A large proportion of people do not consume the recommended fluid amounts. This has likely become worse with our masking during the pandemic.

Previous studies in a mouse model showed that water restriction, increasing serum sodium by 5 mmol/l, shortened the mouse lifespan by 6 months which corresponds to about 15 years of human life.

Population:  Data from Atherosclerosis Risk in Communities (ARIC) study: an ongoing population-based prospective cohort study in which 15,792 45-66 year-old black (African American) and white men and women were enrolled from four US communities in 1987–1989 and followed up for more than 25 years.

Variables:  15 biomarkers and serum sodium (as a proxy for the hydration habits of study participants).

They attempted to exclude people whose serum sodium could be affected by factors other than the amount of liquids they consume. After these exclusions, 11,255 participants remained in the datase.

Authors also calculated ones biologic age by sampling 15 biomarkers characterizing performance of multiple organ systems and processes: cardiovascular (systolic blood pressure), renal (eGFR, cystatin-C, urea nitrogen, creatinine, uric acid), respiratory (FEV), metabolic (glucose, cholesterol, HbA1c, glycated albumin, fructosamine), immune/inflammatory (CRP, albumin, beta 2-microglobulin).

Conclusions: The analysis showed that middle age serum sodium >142 mmol/l is associated with a 39% increased risk to develop chronic diseases (hazard ratio [HR] = 1.39, 95% confidence interval [CI]:1.18–1.63) and >144 mmol/l with 21% elevated risk of premature mortality (HR = 1.21, 95% CI:1.02–1.45). People with serum sodium >142 mmol/l had up to 50% higher odds to be older than their chronological age (OR = 1.50, 95% CI:1.14–1.96).

Limitations:  Observational study. No firm conclusions without intervention studies.

Summary: Serum sodium concentration exceeding 142 mmol/l is associated with increased risk to be biologically older, develop chronic diseases and die at younger age.

Take home:  Drink more water

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An Uncommon Cause of Shock

• Sepsis is the most common cause of distributive shock encountered in the emergency department and intensive care unit.
• Notwithstanding, it is important to consider other etiologies of shock, especially when the patient is not responding to resuscitation.
• Adrenal crisis is one uncommon etiology of distributive shock whereby the diagnosis is often delayed.
• Risk factors for adrenal crisis can include recent GI illness, thyrotoxicosis, recent surgery, and physical or psychological stress.
• Patients often have nonspecific symptoms of generalized weakness, abdominal pain, vomiting, fever, and altered mental status.
• Current guidelines recommend the administration of 100 mg of hydrocortisone in adults suspected of having adrenal crisis.   

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