UMEM Educational Pearls

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Analgesics & Sedatives in the Critically Ill Obese Patient

• Analgesic and sedative medications are frequently administered to critically ill patients.
• Weight-based dosing regimens for these medications can lead to significant over-, or under-, dosing in the critically ill obese patient (BMI > 40 kg/m²).
• In order to avoid harm, it is important to know when to use actual body weight (ABW), ideal body weight (IBW), or adjusted body weight in weight-based dosing regimens.
• Recommendations for weight-based dosing regimens for commonly used analgesic and sedative medications include:
  • Opioids: use IBW or adjusted body weight
  • Ketamine: use IBW or adjusted body weight
  • Propofol: use IBW or adjusted body weight
  • Etomidate: use adjusted body weight or ABW
  • Midazolam: use IBW or adjusted body weight

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Sickle cell trait (SCT) is common and often overlooked clinically

               -7.3% African Americans

               -0.7% Hispanics

               -0.3% Caucasians

SCT is a leading cause of exertional death in athletes who play football

The exact mechanism is unknown but likely involves a combination of high intensity exercise, dehydration, heat strain and inadequate opportunity for cardiovascular recovery leading to microvascular erythrocyte sickling.

This leads to hypoxia, cell death, hyperkalemia, and death from arrhythmia.

Presentation often involves rhabdomyolysis and exertional collapse.

In August of 2010 the NCAA enacted legislation requiring documentation of SCT status of all Division 1 athletes (2012 for Division 2 and 2014 for Division 3)

They also mandated education, counseling and issued guidelines for proper conditioning

Sudden death in athletes with SCT was first observed in military recruits in 1970.

Death in African American military recruits was 28 times more likely in those with SCT than in those without.

A 2012 study of football athletes found the risk of exertional death to be 37 times higher in athletes with SCT than in those without.

Despite game/competition situations being more intense, deaths occur almost exclusively during practice and conditioning drills.

Following the 2010 legislation, there has been a 89% decrease in death from SCT in NCAA D1 football.

Workout plans need to account for heat/humidity, the athletes level of conditioning and allow for adequate rest, recovery, hydration. SCT screening is only part of the solution.

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Question

A 27 year-old man with history of rheumatoid arthritis presents to the emergency department after ingestion of hydroxychloroquine (20 tablets of 200 mg/tablet). He complains of nausea/vomiting. He appears lethargic. What is the anticipated hydroxychloroquine toxicity and management?

VS: Temp: afebrile, BP: 95/55 mmHg, RR: 23 breaths/min, O2 saturation: 99%

ECG:

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• The hormonal changes and hypercoagulable state associated with pregnancy can contribute to neurological conditions.
• Migraine
  • Migraines decrease in frequency through second trimester with increased estrogen, while increase in frequency postpartum with drop in estrogen, stress, and sleep deprivation.
  • Women with history of migraine have higher risk of preeclampsia (odds ratio 2.87).
• Reversible Cerebral Vasoconstriction Syndrome (RCVS)
  • Pregnancy is a risk factor for RCVS with 2/3 of cases of pregnancy-related RCVS occurring in the postpartum period.
• Cerebral Venous Thrombosis (CVT)
  • CVT is associated with the hypercoagulable state in late pregnancy and postpartum period, though often associated with additional source of hypercoagulability.
  • Other risk factors include older maternal age, cesarean delivery, smoking, and dehydration.
• Bell’s Palsy
  • Bell’s Palsy is more prevalent in pregnancy, occurring in the third trimester and the first week postpartum.

Bottom Line: Pregnancy is associated with an increased risk for RCVS, CVT, and Bell’s Palsy. Pregnancy also affects the frequency of migraines due to hormonal fluctuations.

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Patient

·         A North America multicenter study involving 821 asymptomatic patients who had exposure to Covid-19-positive patients.  The study was double-blind, placebo-controlled randomized trial.

Intervention

·         Within 4 days of exposure, participants were randomized to receive hydroxychloroquine.  Dose of hydroxychloroquine was 800 mg once then 600 mg in 6-8 hours then 600 mg daily for 4 more days.

·         There were 414 patients in this arm. Median age 41 years [IQR 33-51]

Comparison:

·         Placebo treatment.  There were 407 patients in this arm. Median age 40years [IQR 32-50]

Outcome:

·         Incidence of either laboratory-confirmed Covid-19 or Covid-19 symptoms within 14 days.

Results:

·         49 (11.8%) patients with treatment had Covid-19 findings (positive tests or symptoms)

·         58 (14.3%) patients with placebo had Covid-19 findings (p=0.35). 

·         The absolute difference was -2.4%.  The number need to treat (NNT) to prevent one infection is 42 patients.  Number needed to harm is 50 patients.

·         Symptoms were fatigue (49.5%), cough (44.9%), sore throat (40.2%) myalgia (37.4%), fever (34.6%), anosmia (23.4%), shortness of breath (18.7%).

Conclusion:

Hydroxychloroquine prophylaxis did not prevent post-exposure Covid-19 infection.

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While taking metronidazole it is advised that patients avoid ethanol use for at least 3 days after therapy due to the possibility of a disulfiram-like reaction.  The disulfiram-like reaction presents as abdominal cramps, nausea, vomiting, headaches, and/or flushing and can cause extreme discomfort for patients.  A recent case report describes a case of a disulfiram-like reaction in a patient receiving metronidazole and an oral prednisone solution that contained 30% alcohol.  This case highlights an important point.  Not only should we counsel patients about avoiding alcoholic beverages for at least 3 days after metronidazole therapy, but they should also avoid all alcohol-containing products, such as oral solutions and mouthwash.

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Clinical Question: Will resuscitation guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?

Methodology:

Design: Randomized, unblinded clinical trial among adults with sepsis-associated hypotension comparing PLR-guided SV responsiveness as a guide for fluid management (intervention) versus “usual care” at 13 hospitals in the United States and the United Kingdom (randomization was in a 2:1 allocation of SV-guided to usual care).

Inclusion criteria:

-patients presenting to the ED with sepsis or septic shock and anticipated ICU admission.

-refractory hypotension (MAP ≤ 65mmHg after receiving ≥ 1L and < 3L of fluid)

Exclusion criteria:

-infusion of > 3L of IV fluid prior to randomization

-hemodynamic instability due to active hemorrhage

-pregnancy or being incarcerated

-indication for immediate surgery

-acute CVA, acute coronary syndrome, acute pulmonary edema, status asthmaticus, major cardiac arrhythmia, drug overdose, injury from burn or trauma, status epilepticus

-inability or contraindication to passive leg raising

Intervention (in ICU):

-PLRs were performed prior to any treatment of hypoperfusion with either fluid bolus or vasopressors for the first 72 hours after ICU admission or until ICU discharge (whichever occurred first)

-If patient was FR (increase in SV ≥10%) a 500 ml crystalloid fluid bolus was given with repeat PLRs after every fluid bolus

-If the patient was non-FR, initiation or up-titration of vasopressors was prompted with repeat PLRs after significant escalation (an increase of 1 mcg/kg/min norepinephrine)

Results:

-83 patients in Intervention arm, 41 in Usual Care arm

-Both arms received a similar volume of resuscitation fluid prior to enrollment (2.4 ± 0.6 L Intervention vs. 2.2 ± 0.7L Usual Care)

-Positive fluid balance at 72 hours or ICU discharge, was significantly less in the Intervention arm (-1.37L favoring Intervention, 0.65 ± 2.85L Median: 0.53L Intervention vs. 2.02 ± 3.44L Median: 1.22L Usual Care, p=0.02).

-Fewer patients required RRT (5.1% vs 17.5%, p=0.04) or MV in Intervention arm compared to Usual Care (17.7% vs 34.1%, p=0.04)

-ICU length of stay was similar in the two arms  

-There was no difference in overall 30-day mortality (6.3% difference, Intervention: 15.7% vs. Usual Care: 22.0%, 95% CI -21.2%, 8.6%)

Implications:

Although this is a smaller, unblinded (also funded by maker of SV monitoring device) study, Douglas et al. demonstrate that limiting fluid administration using dynamic assessments of fluid responsiveness to guide resuscitation in patients in septic shock is likely safe. In fact, this may actually decrease the need for renal replacement therapy and mechanical ventilation amongst this patient population. At the very least, this study adds to the body of literature showing the harms of excessive fluid administration and positive fluid balance.

Bottom line:

If possible, use dynamic assessments of fluid responsiveness in patients with septic shock to guide interventions, particularly for further resuscitation beyond initial fluid resuscitation (~2 liters in this study).

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Over the past several days, riot control agents have been used against the protest participants (related to Mr. George Floyd’s death). There are 3 widely used riot control “lacrimating” agents: 

1. Mace (2-chloroacetophenone)
2. Pepper spray (capsaicins)
3. Tear gas (O-chlorobenzylidene malonitrile)

These agents (irritants) primarily affect the eye, skin, and respiratory tract.

Mangement:

• Initial management involves copious irritation of the affected area with water. 
• There is limited evidence that decontamination with milk, milk of magnesia, or baby shampoo is better than water. 
• Always consider projectile or blunt trauma that may be associated with the riot-control-related ED visits/complaint. 
• Protect yourself by wearing PPE when evaluating/treating these patients.

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• Although significant data has been accumulated regarding Covid-19 infection in adults, the epidemiologic characters and clinical course descriptions in the pediatric population lags.
• Studies to date report that children have mild self-limiting disease with low mortality, even in Immunocompromised children.
• Less than half have fever.
• However, recent reports of a severe illness similar to Kawasaki Disease and/or toxic shock syndrome have led to the newly dubbed Multisystem Inflammatory Syndrome in Children (MIS-C)
• MIS-C CDC Criteria: <21 years of age, laboratory evidence of inflammation, clinically severe illness requiring hospitalization with multisystem involvement, no alternative diagnosis, and positive Covid-19 test or exposure within 4 weeks of presentation.
• MIS-C seems to spare infants and toddlers, and is mostly described in school aged and adolescent groups.
• MIS-C often begins with fever and GI symptoms (mild vague abdominal pain,diarrhea and/or vomiting). 
• Telltale presentation of an erythematous rash that spares the limbs and is associated with conjunctival injection.  Hence the initial misdiagnosis of Kawasaki and Toxic Shock in the first reported cases.
• MIS-C patients quickly decompensate to severe shock that is often refractory to typical treatments.
• Providers should have a higher index of suspicion for MIS-C in any child who presents with concern for Covid-19 infection with these symptoms, and especially with abnormal vital signs. Closer monitoring of heart rate and blood pressure, which is often neglected is vital.

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ILE is considered as one of the “last resort” therapy in cases of life-threatening drug-induced cardiogenic shock or cardiac arrest. Although there are numerous case reports and case series that showed “successful” or “positive” outcome with ILE, here is no clear evidence that lipid emulsion therapy is effective. 

A group of researcher reviewed the National Poison Data System (NPDS) to investigate the failure of ILE therapy by reviewing the overdose fatalities reported to NPDS between 2010 and 2015.

Result:

• Out of 6026 fatalities, 459 fatal overdose cases received ILE.
• Majority involved either CCB or BB overdose (n=285; 62.1%)

Response to therapy (study cohort)

• No response: 45%
• Unknown response: 38%
• Transient/minimal response: 7%
• ROSC: 7.4%
• Immediate worsening: 3%

Adverse effect (n=49)

• ARDS with hypoxemia: 39
• Lipemia causing delay in laboratory evaluation: 3
• Lipemia causing failure of CRRT filter: 2
• Worsening/new seizure: 2
• Asystole: 2
• Fat embolism: 1

Conclusion

• The number of published cases of failed ILE outnumbers the published cases of ILE success.
• Less than 5% of the patients with CCB or BB overdose had ROSC after ILE therapy.

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Background:

· Empiric broad spectrum antibiotic therapy is a mainstay of the management of critically ill patients with septic shock.

· Vancomycin is widely used for the coverage of potential MRSA infection

• PROS: cheap, widely available, relatively widespread tissue penetration when given IV, and is generally well-tolerated

• CONS: has a complicated dosing regimen requiring specifically-timed serum concentration sampling and subsequent dose changes, frequently subtherapeutic, carries a risk of AKI especially when used concomitantly with piperacillin/tazobactam,¹ as it commonly is during empiric therapy for septic shock.         

· Continuous infusion of vancomycin has been repeatedly demonstrated to reach target serum concentrations faster, maintain consistent serum vancomycin levels better, with fewer serum concentration sampling required, and less overall vancomycin required to do so, in both adult and pediatric populations.^2-5

Current Article: 

Flannery AH, Bissell BD, Bastin MT, et al. Continuous Versus Intermittent Infusion of Vancomycin and the Risk of Acute Kidney Injury in Critically Ill Adults: a Systematic Review and Meta-Analysis. Crit Care Med. 2020;48(6):912-8.

· Systematic review and meta-analysis of 11 studies for a total of 2123 patients

· Comparing continuous versus intermittent vancomycin infusion.

· Primary outcome of AKI, secondary outcome of mortality

· Found a reduction in the incidence of AKI in the continuous infusion cohort:

• OR 0.47 (95% CI 0.34-0.65) even when taking into account trough levels /area under the curve concentrations and the severity of AKI examined by the individual studies.

· No association between infusion strategy and mortality

Considerations:

· Initial loading dose used in most of the studies (15 mk/kg) probably underdosed, current recommendation for 25mg/kg initial loading dose⁷ (which is not even always effective by itself)⁸ (Reardon)

· Continuous infusion may be difficult with limited IV access

· AKI associated with increased hospital stay, costs, mortality (although didn’t pan out in study) – worth preventing if possible.

Take Home:

· Give a 25-30mk/kg loading dose of vancomycin in critically ill patients with suspicion of MRSA to achieve target serum concentrations sooner.

· Continuous vancomycin is a viable option and could be considered in ED boarders, especially if there is concern for impending renal injury.

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Post concussion musculoskeletal injuries

Sport related concussion (SRC) impairs numerous functions of the CNS.

Traditional research has focused on risk of repeat concussion following clearance and return to sport

Several studies have shown a consistent elevated risk of lower extremity injuries from 90 days up to one year following SRC.

These include lateral ankle sprains and ACL injuries. Risk ranges, 1.3-3.4x.

This risk may be greater in those with multiple concussions.

This elevated rate has been seen in populations ranging from high school, college to professional athletes and has also been seen in the general population.

Persistent neurological deficits in cognitive and postural control, stability and gait deviations have been postulated as potential mechanisms.

These may be potential modifiable risk factors before return to play/activity. This may be a role best served by sport physical therapists to assist with sport specific rehabilitation post concussion.

NHTSA recommends that car seats be replaced following a moderate or severe crash. Car seats do not automatically need to be replaced following a minor crash.

A minor crash is one in which ALL of the following apply:

-The vehicle was able to be driven away from the crash site.
-The vehicle door nearest the car seat was not damaged.
-None of the passengers in the vehicle sustained any injuries in the crash.
-If the vehicle has air bags, the air bags did not deploy during the crash
-There is no visible damage to the car seat.

NEVER use a car seat that has been involved in a moderate to severe crash. Always follow manufacturer's instructions.

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Question

A 19 year old man presents with a scalp lesions/burns after an exposure to incendiary agent. His wounds were smoking and they flouresce under UV light. 

What is the causative agent?

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• Previous studies suggest more than 1/3 of head CTs are avoidable by evidence-based guidelines.
• It is controversial whether patients respond to financial incentives for healthy behavior.
• A study by Iyengar et al. surveyed 913 ED patients using a hypothetical mild TBI scenario that does not need a head CT by the Canadian CT Head Rule.
• Patients were randomly assigned the consideration of benefit (0.1% of 1%), risk (0.1% or 1%), or financial incentive ($0 or $100) associated with obtaining a head CT.
• Overall, 54.2% (495/913) patients elected to obtain a head CT.
  • An increase in test benefit was associated with a 9.3% increase in CT use (49.6% to 58.9%).
  • An increase in test risk was associated with a 10.2% decrease in CT use (59.3% to 49.1%).
  • An increase in financial incentive was associated with a 11.7% decrease in CT use (60.6% to 48.3%).

Bottom Line: Discussion of benefit/risk and financial incentive associated with head CT in mild TBI affects patient decision. Interestingly in this population studied, more than half of patients will elect to obtain a head CT even in a low-risk scenario.

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As the debate regarding the pathophysiology and ventilator mechanics of COVID pneumonia rages on, it is important to have a method to evaluate the distensibility of patients' lungs so that we can minimize lung injury.  It has been well shown that both under- and over-distention lead to acute lung injury and inducing or worsening ARDS.

One method to find the "best" level of PEEP is through the PEEP titration test (also called a Driving Pressure titration test).  High Driving Pressure (DP), which is equal to Plateau Pressure - PEEP, has been shown to be associated with lung injury, and the minimal DP obtainable for a given patient while still meeting ventilatory goals is often an objective in the ICU (common DP goal is < 15 cm H2O).  A PEEP titration is optimally done on paralyzed patients, although it can be used on sedated or very calm patients as a "best guess" approximation.  It will not work well on agitated patients or those participating heavily in their ventilation.  Be sure not to do this if you are not authorized to make vent changes, and always make sure to coordinate appropriately with your RT.

To perform a PEEP titration:

*Consider placing the patient on square waveform VC, as this will also allow evaluation of stress index (if patient is not participating).  This can be skipped if not evaluating stress index

1) Make a table for yourself on a piece of paper where you can record PEEP, Plateau Pressure, Driving Pressure, Blood Pressure, and SpO2.

2) Write down the initial PEEP, BP, and SpO2.  Clearly document for yourself that this is the initial PEEP, so you do not inadvertantly leave the vent on different settings at the end.  Perform an inspiratory hold to measure a plateau pressure.  Fill in DP by using the equation DP = Pplat - PEEP

3) Change the PEEP.  You can either increase or decrease.  If you have a suspicion that the patient is over or under distended, go towards optimal distention, but if unsure it is ok to guess.  Usually we go by increments of 2 cm H2O.  Wait about 20-30 seconds on the new PEEP.

4) Measure a new plateau pressure and calculate a new DP.  At each step, write down the BP and SpO2 as well to ensure you are not generating decreased cardiac preload or derecruitment/hypoxia (keep in mind that due to pulse ox lag, you may not see hypoxia for up to a few minutes).  

5) Repeat at a few different PEEP levels.  Typically in more unstable patients who may not tolerate aggressive vent changes you may only want to check 2-3 levels of PEEP.  In more stable patients or if concern for ongoing lung injury is high, you might check up to 5-6 different levels of PEEP.  Please note that some COVID ARDS patients are so unstable that they will not tolerate any derecruitment, and this manuever should not be used in those patients as they could desaturate during the titration.

Once you have all of your data, consider changing to whichever PEEP level gives the lowest driving pressure.  Keep in mind that while data from a PEEP titration can be very useful, it is only one data point and should be considered in combination with blood pressure, volume status, CXR findings, habitus, FiO2 weaning, and other factors.  PEEP titrations should be reperformed periodically (usually daily in most semi-stable ICU patients, more often in unstable patients).  it is also recommended to write a note in the chart with your initial vent settings, data from the titration, and settings upon termination of the titration -- and call your RT if you changed the vent settings.

Bottom Line: PEEP titration (aka Driving Pressure titration) aims to identify the PEEP level where (PPlat - PEEP) is minimal and may help reduce risk of ongoing lung injury in ventilated patients.

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MRI for Concussion Testing in the ED

The increased sensitivity of MRI may have a role in detecting more subtle intracranial injuries.

135 patients with mild TBI were prospectively evaluated for acute head injury in emergency departments of 3 LEVEL I trauma. 

27% of these patients with a normal initial head CT had an abnormal brain MRI including contusions and microhemorrhages. A greater number of these subtle findings was associated with neuropsychological defects on both short-term memory function and with poorer 3 month cognitive outcomes. Inherent difficulties of access, actionable results and reimbursement issues prevent application of MRI for concussion evaluation in the ED.

Note: Mild TBI defined as GCS 13-15 is not the same as sport or activity related concussion which I consider to be GCS 14-15.

Take home: There is currently no role for MRI in the acute evaluation of concussion in the ED.

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If you have an intuition your patients older than 65 are at increased risk of infection, especially pneumonia (4-11 times the risk of the under 65 cohorts), you are correct.

If you are concerned your patients co-morbidities, such as COPD, heart disease, and malnutrition will contribute to prolonged mechanical ventilation (the rate of VAP increases 1-3% every extra day on the vent), you are correct.

After age 70, the ICU length of stay and duration of mechanical ventilation increase by 5 days and 9 days respectively. 

In the age of COVID-19, itself associated with prolonged mechanical ventilation, it's fair to prepare patients and families for this. We are fortunate we do not need to ration ventilators, so our discussions remain centered on the wishes of our patients, informed by a realistic understanding of what treatment and recovery entail.

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