UMEM Educational Pearls - Critical Care

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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Takeaways

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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Vitamin C for Septic Shock?

• In 2017, a single center before-and-after study demonstrated benefit for patients with sepsis who received vitamin C, hydrocortisone, and high-dose thiamine.
• At present, there are more than 30 trials evaluating the use of vitamin C in sepsis.
• The VITAMINS Trial was recently published and evaluated shock resolution in patients with septic shock who received vitamin C, hydrocortisone, and high-dose thiamine compared to those that received only hydrocortisone.
• In this randomized controlled trial of 211 ICU patients, the authors found no difference in the primary outcome of time alive and free of vasopressors at 7 days between the two groups.
• There was also no difference in the secondary outcomes of hospital, 28-day, and 90-day all-cause mortality.
• Though we still await the results of ongoing trials, the VITAMINS Trial and the recent CITRIS-ALI Trial have not demonstrated benefit of vitamin C for select patient populations with sepsis.

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Title: Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus

Settings:

• 57 US hospitals: 26 sites for adults only, 18 sites enrolling only children, 13 sites enroll both.

Patients:

• 384 patients whose ages were 2 years and older. 
• Patients who continued to have generalized seizure for at least 5 minutes after “accepted” cumulative dose of benzodiazepines.

Intervention:

• levetiracetam at a dose of 60 mg per kilogram (maximum, 4500 mg),
• Fosphenytoin at a dose of 20 mg PE per kilogram (maximum, 1500 mg PE),
• valproate at a dose of 40 mg per kilogram (maximum 3000 mg)

Comparison:

• Patients > 32 kg total body weight:  diazepam of 10 mg; Lorazepam 4mg Intravenously; midazolam 10 mg intravenously or intramuscularly.
• Patients < 32 kg total body weight: diazepam at a dose of 0.3 mg per kilogram (administered intravenously or rectally), lorazepam at a dose of 0.1 mg per kilogram (administered intravenously), or midazolam at a dose of 0.3 mg of per kilogram (administered intramuscularly) or 0.2 mg per kilogram (administered intravenously)

Outcome: absence of clinical seizure at 60 minutes after infusion of medication.

Study Results:

• Rates of cessation of status epilepticus were similar in all 3 groups: 47% of levetiracetam vs. 45% Fosphenytoin vs. 46% for valproate.
• Fosphenytoin was associated with non-significantly higher rate of hypotension (3.2%) vs other drugs.
• Levetiracetam was associated with non-significantly higher rate of death (4.7%) vs. other drugs.
• All three medication was associated with similar rate of intubation within 60 minutes of drug infusion.

Discussion:

• The median time interval from start to cessation of status epilepticus appeared to be shorter for valproate but there was no formal analysis yet,
• Valproate (7.0 minutes) vs. levetiracetam (11.7 minutes) vs. Fosphenytoin (11.7 minutes)

Conclusion:

• Three medications, Fosphenytoin, levetiracetam, valproate were equally effective.

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Clinical Question: Does a lower MAP target (60-65 mmHg) for ICU patients ≥ 65 years-old reduce 90-day mortality?

Methodology:

-Design: multicenter (across 65 UK ICUs), randomized clinical trial (not blinded), ultimately with 2598 patients

-Inclusion criteria: ICU patients ≥ 65 years-old receiving vasopressors for vasodilatory hypotension with adequate fluid resuscitation

-Exclusion criteria: vasopressors being solely used for bleeding or acute RV/LV failure or post-cardiopulmonary bypass vasoplegia, ongoing treatment for brain/spinal cord injury, death perceived as imminent

-Intervention:

• Permissive hypotension group – MAP target of 60-65 mmHg
• Usual care group – received vasopressors at discretion of treating clinician
• Choice of vasopressor (norepi, vaso, terlipressin, phenylephrine, epi, dopamine, and metaraminol) left to discretion of treating clinician

Results:

-Patients in the permissive hypotension group had a lower exposure to vasopressors compared with those in the usual care group

• median duration 33 hours compared with 38 hours (difference, –5.0; 95% CI, –7.8 to –2.2)
• mean duration, 46.0 hours compared with 55.9 hours (mean difference, –9.9 hours; 95% CI, –14.3 to –5.5)

-Mean MAP was on average 6 mmHg lower in permissive hypotension group

-At 90 days, there was no statistically significant difference in all-cause mortality

• 500 deaths (41.0%) among of 1221 patients in the permissive hypotension group compared with 544 (43.8%) among 1242 patients in the usual care group (absolute risk difference, −2.85%, 95% CI, −6.75 to 1.05; P = .15)

-No significant difference in mean duration of ICU and hospital stay, duration and days alive and free from advanced respiratory and renal support to day 28

-No significant different in number of serious adverse events (severe acute renal failure, supraventricular and ventricular cardiac arrhythmia, myocardial injury, mesenteric ischemia, and cardiac arrest)

Bottom line:

A lower MAP goal of 60-65 mm Hg appears to be safe for ICU patients ≥ 65 years-old being treated for vasodilatory hypotension

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There is currently a high, and appropriate, concern regarding the aerosolization of viral particles during various methods of respiratory support. While studies are limited, here is some of the currently available data (mostly-simulated) on the approximate maximum distances of particle spread:

Nasal Cannula 5LPM:¹ 1 ft 4.5 in

Non-Rebreather Mask, 6-12LPM: 4 in, minimal change with increasing flows¹

High Flow Nasal Cannula

• Simulation:² 30 LPM = 5.6 in / 60 LPM = 8.1 in
• Actual volunteers:³
  • Use of HFNC decreased aerosol dispersion during “violent exhalation” through nares
  • No difference in aerosol dispersion w/normal breathing using HFNC until 60lpm
  • Max spread = 14.4 ft without HFNC (violent exhalation) and 6.2 ft with HFNC (violent exhalation); aerosols airborne for max of 43 seconds

CPAP (20 cmH2O) provided by oronasal mask with good fit (leak from exhaust port):² 11.5 in

Bilevel positive airway pressure w/ oronasal mask (IPAP 10-18/EPAP 4): max dispersal:⁴ 1 ft 7.7 in

Bilevel positive airway pressure with full facemask⁵ (IPAP 18 / EPAP 5): 2 ft 8 in

Bilevel positive airway pressure with helmet:⁴

• IPAP 20 / EPAP 10 = 9 in
• Using helmet w/ air cushion = negligible dispersal

Utility of Surgical Mask:⁶

• No therapy:                 31% of exhaled particles travel, some >3.3 ft
• No therapy + mask:    5% of exhaled particles leak, some >3.3 ft
• 6LPM O2 + mask:       6.9% of exhaled particles leak, some >3.3 ft
• High Velocity Nasal Insufflation (40LPM) + mask: 15.9% of exhaled particles leak, some >3.3 ft

Bottom Line: 

In vivo data from actual patients is lacking, however there is potentially lower risk of aerosol spread with HFNC than regular nasal cannula, perhaps due to higher likelihood of a tighter nare/nasal cannula interface. Nonrebreather mask performs well indirectly with the shortest dispersal distance. Noninvasive positive pressure ventilation with an oronasal mask and good seal has a relatively short dispersal distance, and a surgical mask over respiratory support interventions actively decreases amount, if not distance, of particle spread. Use of appropriate PPE and negative pressure rooms, if available, remains key.

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Please see Part I from 12/24/19 for information about causes and symptoms.

Diagnosis:

The diagnosis of HLH is challenging, as it often mimics sepsis or other critical illness.  A high index of suspicion is vital and early treatment, imperative.

Diagnostic criteria in adults include 5 of 8 of the following:

(based on the Hscore:  https://www.mdcalc.com/hscore-reactive-hemophagocytic-syndrome#use-cases)

·      Presence of known immunosuppression

·      Fever >38.5

·      Splenomegaly or hepatomegaly

·      Cytopenias

·      Ferritin elevation (usually markedly elevated)

·      Elevated triglycerides

·      Low fibrinogen level

·      ALT elevation

Immunologic testing:

·      CD25 levels are elevated

·      NK cell activity is low or absent

In adults, highly elevated ferritin levels (>10,000) are highly suggestive of HLH.

Elevated LDH, Ddimer, and multisystem organ dysfunction (especially CNS) is common.

Immunologic testing should not delay treatment if other lab values suggestive of HLH.

Treatment:

Given the high mortality rate, treatment should be initiated if the symptoms are suggestive of HLH.  In the setting of a critically ill individual, hematology consultation is warranted for treatment guidance as treatment is based on lab values and clinical picture. Treatment usually starts with high dose , IV steroids (dexamethasone) and may include chemotherapeutic agents, such as Etoposide. For those patients with CNS involvement, intrathecal chemotherapy is usually a mainstay of treatment

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Within the past few days we completed a review of complications of COVID-19, to describe what sequelae and clinical patterns, besides the obvious (URI, respiratory failure, ARDS, sepsis, etc), are noted in the literature.  This review, along with a plethora of other information focusing on critical care of the COVID-19 patient, will be posted in the next few days to http://covid19.ccproject.com/.  Below are the key points from that review:

• Acute cardiovascular complications appear to be the most common and concerning sequelae:  

                 -Acute myocardial injury (7-17% of hospitalized patients in one study),   

                 -Myocarditis (primary cause of death in 7% of COVID deaths in one study),  

                 -Arrhythmias (16.7% of hospitalized and 44.4% of ICU patients in one study), 

                  -Venous thromboembolism (incidence unknown).   

• Concerns for sudden cardiac death, even after recovery, have been raised but are not well documented in the literature.  Proposed mechanisms include respiratory compromise, myocarditis, malignant tachydysrhythmias, heart failure, and coronary plaque instability (i.e. Type 1 MI) secondary to inflammation 

• Co-infection and secondary infection rates are unknown but estimates range from 4.8% to 21%, with higher rates in sicker patients. Viral co-infection is more common than bacterial co-infection, but both may be seen. The ability to rule out COVID-19 by a positive multiplex respiratory viral panel is questionable. 

• Cytokine release syndrome and secondary HLH are both described complications, but their incidence is unknown.  The relation of this finding to purported benefits of tocilizumab (which is also a therapy for HLH) is unknown. 

• Other extrapulmonary complications are relatively typical of sepsis, such as kidney injury, abnormal LFTs, and delirium 

If anyone would like a copy of the full document, which details known complications by organ system, please feel free to email me at msutherland@som.umaryland.edu.  Thanks to David Gordon for organizing the project.

Everyone stay safe, and be sure to take care of each other, as well as our patients.

Takeaways

This week we anticipate treating more COVID19 cases as they progress to ARDS. The World Health Organization issued guidelines on 3/13/20 for treating Severe Acute Respiratory Infection (SARI) due to COVID19. 

How to identify ARDS?

No different than before COVID. Order a CXR, ABG, and perform bedside ultrasound evaluation of cardiac function and volume status. If there are bilateral opacifications you cannot explain entirely with volume overload, nodules, or lobar collapse, AND if the ratio of PaO2/FiO2 is < 300 (mild), < 200 (moderate), or < 100 (severe), then treat for ARDS.

***While you are waiting for your blood gas, SpO2/FiO2 <315 suggests ARDS.

What is the oxygen goal?

During resuscitation: > 93%

Once stabilized: > 89%

What is the expected clinical course?

Patients experience RAPID deterioration to respiratory failure. You should expect to intubate. This should be performed with N95 protection and should be done by the person with greatest first pass success.

Be CONSERVATIVE with fluids. Do not give a 30mL/kg bolus. Give 250-500mL bolus and re-evaluate. Excess fluid results in prolonged hypoxia and mechanical ventilation.

Should empiric treatments change?

No. Co-infection with influenza, bacterial pneumonia, and all other pathogens is possible, so you should continue to cover all suspected pathogens and de-escalate as microbiology labs result.

Should ventilator settings change?

No. Use lung protective volumes and permissive hypercapnia. The volume is based on the patient's height, not weight. A quick way to do this? Measure the height in cm. Subtract 100 for a man and subtract 110 for a woman and this is the ideal body weight. Provide 6mL/kg of tidal volume with a goal plateau pressure < 30. Use the high PEEP strategy from the ARDSnet trial and even consider clamping the ET tube when transitioning from machine to bag for transport in order to preserve PEEP.

Do patients benefit from proning?

Yes. 12-16 hours/day for severe ARDS. Not true in pregnancy as a whole, though early pregnancy may still benefit.

 Is ECMO beneficial in refractory cases?

Unknown. In the case of MERS-CoV, ECMO reduced mortality.

Are corrticosteroids useful?

No. Do not administer steroids routinely to these patients. You may give steroids where indicated, including cases of refractory shock following pressors.

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(*It is important to note that many of the percentages in these early studies will change as more asymptomatic or minimally symptomatic patients are identified with increased testing)

Epidemiology

Among more than 44,000 confirmed cases of COVID-19 in China as of Feb 11, 2020:

- 30–69 years: ~78%

- severely or critically ill: ~19%

Case-fatality proportion: 

-60-69 years: 3.6%

-70-79 years: 8%

-≥80 years: 14.8%. 

-With no underlying medical conditions: overall case fatality of 0.9%

-With comorbidities: 

-cardiovascular disease (10.5%), diabetes (7%)

-chronic respiratory disease, hypertension, and cancer (6% each)

Presentation

For patients admitted to the hospital, many non-specific signs and symptoms: 

- fever (77–98%) and cough (46%–82%) were most common

- of note, gastrointestinal symptoms (~10%) such as diarrhea and nausea present prior to developing fever and lower respiratory tract signs and symptoms.

Diagnosis

No general lab tests have great sensitivity or specificity            

A normal CT scan does NOT rule out COVID-19 infection

-In an early study, 20/36 (56%) of patients imaged 0-2 days (‘early’) after symptom onset had a normal CT with complete absence of ground-glass opacities and consolidation

Treatment-

Mainstay of treatment will be management of hypoxemia including early intubation if necessary. However, specifically:

-Steroid therapy is controversial and the WHO is currently recommending against it unless it is being administered for another reason

-has not been associated with any benefit

-associated with possible harm in previous smaller studies with SARS and MERS

-associated with prolonged viremia

-intravenous remdesivir (a nucleotide analogue prodrug with promising in-vitro results against SARS-CoV and MERS-CoV) is available for compassionate use

            -lopinavir-ritonavir has been used without any associated benefit

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Settings: Multicenter randomized controlled trial

Patients: 710 patients

Intervention: 345 patients.  no sedative but only boluses of morphine as clinically indicated (Sedation group)

Comparison: 356 patients.  light sedation with daily interruption (Nonsedation group)

Outcome: all-cause mortality at 90 days after randomization

Study Results:

42.4% of nonsedation group died vs 37% of sedation group (95% confidence interval [CI], −2.2 to 12.2; P = 0.65). 

Number of ventilator-free days for nonsedation group was 27 days vs. 26 for sedation group. 

Discussion:

This study did not agree with previous studies that lighter sedation was associated with shorter length of stay on mechanical ventilation , ICU or hospital.  The authors attributed to the findings that RASS score was not significantly different between the 2 groups.

Conclusion:

Critically ill adult patients receiving mechanical ventilation, there was no difference in 90-day mortality between patients receiving light sedation or no sedation.

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With ED-boarding of critically-ill patients becoming more common, it is likely that ED physicians may find themselves caring for a patient who develops ACS – that is, abdominal compartment syndrome. While intraabdominal hypertension (IAH) is common and is defined as intraabdominal pressure > 12 mmHg, ACS is defined as a sustained intraabdominal pressure > 20mmHg with associated organ injury.

WHY you need to know it:

ACS → Increased mortality & recognition is key to appropriate management

WHO is at risk:

• Decreased abdominal wall compliance (obese, post-surgical)
• Increased intrabadominal contents (hemoperitoneum, ascites, tumor)
• Increased intraluminal contents (gastroparesis, ileus)
• Capillary leak / aggressive fluid resuscitation (sepsis, burns)

HOW it kills:

• Decreased blood flow to organs due to extraluminal pressure (mesenteric, renal, hepatic ischemia)
• Decreased diaphragmatic mobility, hypoventilation/oxygenation
• Decreased venous return, decreased cardiac output

→ Lactic acidosis, respiratory acidosis, multisystem organ failure, cardiovascular collapse & death

WHEN to consider it:

• Most patients who develop ACS are already intubated or altered – but consider in responsive patients c/o severe abdominal pain, marked distension, and SOB with tachypnea
• Intubated patients – recurrent, ongoing high pressure alarms with relatively low lung volumes, tachypnea
• Abdomen distended and minimally ballotable
• New / worsening oliguria / anuria
• Labs demonstrate increased creatinine, LFTs, lactate elevated “out of proportion” to patient presentation prior to decompensation 
• Imaging may reveal underlying etiology or sequelae of ACS but cannot rule it out

WHAT to do:

1. Confirm diagnosis with bladder pressure (via urinary catheter) *see cited paper for how-to in the ED*
2. Emergent surgical consultation (emergent laparotomy → improved hemodynamics, organ function, & survival. 
3. Optimize abdominal perfusion pressure (MAP - intraabdominal pressure; recommended > 60mmHg) as much as possible:

• Adequate analgeisia and sedation, if needed, to avoid agitation
• Avoid intubation if able, to avoid the positive pressure. In intubated patients, aim for low PEEPs and plateau pressures and consider short-term paralytic
• Lower the head of bed (supine to 30mmHg) to minimize abdominal "crunch"
• Aim for intravascular euvolemia. If volume overload is a contributing factor then IVF for hypotension will worsen the ACS -- start vasopressor instaed
• Evacuate intraluminal contents if able (NGT/rectal tube for decompression, consider erythromycin/reglan, or neostigmine for colonic pseudoobstruction)
• Evacuate intraabdominal extraluminal contents if able (therapeutic paracentesis for ascites(
• Burn patients with restrictive abdominal eschar should get escharotomy

Bottom Line: Abdominal compartment syndrome is an affliction of the critically ill, is assosciated with worsened mortality, and requires aggressive measures to lower the intraabdominal pressure while obtaining emergent surgical consultation for potential emergent laparotomy. 

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Don't forget cerebral fat embolism syndrome (FES) on the differential for altered trauma patients.  FES is typically associated with long bone fractures, but has been reported with other fractures, orthopedic reaming (i.e. aggressive orthopedic procedures), and in rare cases even with non-fracture (soft-tissue) trauma.  Typically symptoms occur between 24 and 72 hours after injury, but there have been cases both earlier and later.  Diagnosis is clinical, but MRI may be helpful, and will often show multiple cerebral white matter lesions.  It is debated whether FES is truly an embolic phenomena (i.e fat molecules traveling to and blocking blood supply of organs), or rather an inflammatory response to free fatty acids in the blood stream (i.e. more of a vasculitis type pathology).  Management is supportive care, but give these patients time as there can be favorable outcomes, even after prolonged coma.

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Takeaways

Dr. Bryan Hayes wrote a Pearl 10/4/2013 to remind us autoimmune encephalitis can present like neuroleptic malignant syndrome.

Dr. Danya Khouja wrote a Pearl 6/28/2017 to inform us autoimmune encephalitis is associated with tumors and can be investigated with serum and CSF antibody panels.

Since those publications, the number of validated autoimmune biomarkers in these panels has increased dramatically. In 2020 we now know, autoimmune encephalitis is at least as common as infectious encephalitis.

Here is how to diagnose it

1. Suspect the diagnosis in patients with subacute/rapidly progressive altered mental status, memory loss, or psychiatric symptoms. It can be mistaken for a new diagnosis of schizophrenia or bipolar disorder. 

2. Look for one or more additional findings: new seizures, focal CNS findings, CSF pleocytosis, MRI findings

3. Exclude other likely etiologies (but try not to get hung up on a positive drug test, especially if drug use was not recent).

Why is this important?

Early treatment with steroids and plasmapheresis can prevent progression of disease (prevent seizures, prevent months-long hospitalizations).

Young girls are especially likely to have teratomas as a cause for the disease. Finding and resecting those tumors is life-saving.

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Mechanical Ventilation Pearls for Acute Ischemic Stroke

• Patients with an acute ischemic stroke (AIS) may require intubation for various reasons.
• Two main goals of mechanical ventilation in patients with an AIS are to maintain appropriate oxygen levels and tight control of PaCO2.
• In terms of oxygenation:
  • Target normoxia
  • Administer O2 if the SpO2 is < 94%
  • Supplemental O2 is not recommended in non-hypoxic patients
• In terms of CO2:
  • Target normocapnia
  • Hypercapnia increases the risk of intracranial hypertension
  • Hypocapnia can worsen cerebral perfusion

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Settings: multicenter, double-blind, phase 3 trial (apparently vitamin D worked in phase 2 trials).

• Patients:
  • 1059 patients were enrolled within 12 hours of ICU admission.  The patients had to have risk factors warranted ICU admisions (pneumonia, sepsis, mechanical ventilation, shock, pancreatitis, etc.).
  • Vitamin D deficiency was defined as plasma level < 20 ng/ml
• Intervention:
  • 531 patients received a single oral dose of 540,000 IU of vitamin D3 within 2 hours after randomization
• Comparison
  • 528 patients received placebo
• Outcome
  • 90-day all-cause mortality

Study Results:

• Total SOFA score was similar in both groups (5.6 vs. 5.4).               
• On day 3, mean plasma vitamin D was higher (47 ng/ml) in treatment group vs 11 ng/ml in placebo group
• 90-day all cause mortality was similar.  Treatment group was 23.5% vs. 20.6% for placebo (95% CI, −2.1 to 7.9; P = 0.26).
• Vitamin D-related adverse events were similar in both groups.

Discussion:

• This trial enrolled patients early in their critical illness compared to phase 2 trial which enrolled patients after 3 days in the ICU.
• This phase 3 trial also enrolled mostly medical-related illness, whereas 75% of patients in phase 2 had either surgical or neurology-related illnesses.

Conclusion:

Early administration of high dose vitamin D did not improve 90-day all cause mortality.

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The arrival of a critically ill pregnant patient to the ED can be anxiety-provoking for emergency physicians as two lives and outcomes must be considered.

Some basic tenets of care, regardless of underlying issue, include:

• Obtain IV access above the diaphragm to avoid delay/prevention of administered products reaching central circulation due to compression of the IVC by the gravid uterus. 

• Provide supplemental oxygen as needed to maintain a saturation of >95% which corresponds to a PaO2 >70 mmHg. A PaO2 <60 mmHg is associated with fetal hypoxemia which will quickly lead to fetal acidosis and bradycardia. 

• Goal maternal PaCO2 is 28-32 mmHg; this respiratory alkalosis maintains a CO2 gradient to help shift offload fetal CO2 into the maternal circulation for clearance. 

• Hypotensive pregnant patients with a large uterus (20+ weeks) should be turned to the left lateral decubitus position or tilted leftward by at least 15 degrees to offload aortocaval compression and minimize secondary decrease in venous return) by the gravid uterus. 

• In cases of maternal cardiac arrest, the patient should be kept supine for chest compressions with the gravid uterus manually displaced to the left.

• Keeping the mother alive is the best way to keep the fetus alive. Standard sedatives, vasopressors, and inotropes are okay if they are needed. Exception for ketamine, which has mixed effects in existing studies and while low doses are probably safe if needed, use as a firstline agent is not recommended. Notify the NICU team of medications given to mother if there is a precipitous delivery.

• Fetal tococardiometry monitoring if available, or regular POCUS assessment of FHR, in all viable pregnancies.

Finally, once critical illness is identified the OB and NICU teams should be consulted immediately. Fetal distress in a viable pregnancy may be an indication for delivery, and initiation of the transfer process should occur if the supportive specialties are not in-house.

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There are few conditions that can be as dramatic or difficult to control as variceal GI bleeding in a cirrhotic patient.  It is important to be familiar with all options in these cases, from Blakemore/Minnesota tube placement to massive transfusion to when and which consultants to get involved.  In cases that are refractory or not amenable to endoscopic intervention, emergent interventional radiology consultation for Transjugular Intrahepatic Portosystemic Shunt (TIPS) may be a consideration.  In high risk cases, think about getting IR on the phone at the same time as you engage GI, in case endoscopic management fails.  Variceal bleed patients can decompensate rapidly, get your consultants involved early!

Generally accepted indications for emergent TIPS (both of the following should be true):

-GI bleeding not amenable or not controllable by endoscopy

-Cause is felt to be variceal. May also consider in portal hypertensive gastropathy

Contraindications:

-Right heart failure or pulmonary hypertension

-Severe liver failure (MELD > 22, T Bili > 3 or Child-Pugh C. In these cases TIPS may not confer a significant survival benefit)

-Hepatic encephalopathy (relative contradindication.  HE may be worsened by TIPS).

-Polycystic liver disease (makes TIPS technically challenging)

-Chronic portal vein thrombus (makes TIPS technically challenging. Acute PV thrombus is NOT considered a contraindication)

Bottom Line: In cases of variceal GI bleeding from portal hypertension, consider getting IR on the phone early to discuss emergent TIPS.

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Takeaways

Pearl: consider desmopressin (DDAVP) for patients with an intracranial hemorrhage who are taking an antiplatelet. Caution, this is not for patients with an ischemic stroke with hemorrhagic conversion and it was not specifically evaluated for patients on anticoagulation or going to the OR with neurosurgery.

How strong is this evidence? International guidelines already give cautious approval for this practice, and now there is a retrospective review to support it. Though there were only 124 patients in the trial, the rate of hemorrhage expansion was much lower in the DDAVP group (10.9% vs 36.2%, P = .002) and there was no increased risk of hyponatremia (no events reported).

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Interventions Shown to Reduce Mortality in RCTs

• Santacruz and colleagues recently performed a systematic review to determine which multicenter RCTs in critically ill patients have shown that an intervention was associated with a reduction in mortality.
• Approximately 13% of the 212 trials included in this review reported a statistically significant reduction in mortality.  Unfortunately, many of the interventions were not associated with reduced mortality in subsequent studies.
• Interventions consistently shown to reduce mortality in multicenter RCTs in critically ill patients were limited tidal volume in patients with ARDS, noninvasive ventilation in acute hypercapnic respiratory failure, and noninvasive ventilation following extubation in complex cases.
• Corticosteroids in septic shock, selective digestive decontamination, and prone positioning in ARDS remain controversial.

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