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Respiratory Complications of ICIs

• Acute respiratory failure (ARF) is the leading cause of ICU admission for immunocompromised patients.
• While infectious etiologies remain the most common cause of ARF in these patients, there is an increasing prevalence of non-infectious, treatment-related causes.
• Immune check-point inhibitors (ICIs) are now used with increasing frequency, and can cause severe pulmonary toxicity in approximately 6% of patients.
• Pearls for ICI pulmonary toxicity include:
  • Acute pneumonitis is the most common presentation
  • Median time of onset of approximately 4 months after treatment initiation
  • Symptoms include dry cough, hypoxemia, and infiltrates not c/w CHF, infection, or progression of malignancy
  • Treatment is to DC the ICI and initiate steroids

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When caring for a patient with a laceration we often do lcoal infiltration prior to suturing but remember the benefits of regional nerve blocks

Benefits of Regional Nerve Blocks

• Less Painful
• Prevents distortion of the wound which can help with cosmetic closure
• Allows for a greater area to be anesthesized with less anesthetic use (prevents toxic levels)
• Can allow for longer anesthetic time

Quick reminder of properities of common anesthetic

Final reminder:  There is no evidence that epinephrine causes necrosis and it can be used safely in digital blocks. Duration of action is max 90 minutes. Even individuals that have injected themselves with EpiPens into their hands have not had any long term sequelue or necrosis seen. Vast majority required no treatment at all.

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Post tonsillectomy hemorrhage occurs and 0.1-3% of post tonsillectomy patient's.  It occurs typically greater than 24 hours after surgery and up to 4-10 days postoperatively.  A survey of otolaryngologists showed that ED management strategies for active bleeding have included direct pressure, clot suction, silver nitrate, topical epinephrine, and thrombin powder.

This article was a case study demonstrating the use of nebulized tranexamic acid (TXA) for post tonsillectomy hemorrhage in a 3-year-old patient.  The patient had a copious amount of oral bleeding and had failed treatment with nebulized racemic epinephrine and direct pressure was not an option due to the patient's cooperation and small mouth.  250 mg of IV TXA was given via nebulizer with a flow rate of 8 L.  Bleeding stopped 5-7 minutes after completion of the nebulizer.  The patient was then taken to the OR for definitive management.  No adverse effects were noticed.

TXA in the pediatric population has been shown to decrease surgical blood loss and transfusions in cardiac, spine and craniofacial surgeries.  Studies have also been done in pediatric patients with diffuse alveolar hemorrhage using doses of 250 mg for children less than 25 kg and 500 mg for those who are greater than 25 kg.

Bottom line: There are case reports of nebulized TXA use in the pediatric population with no adverse outcomes noted.  More research is needed.

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--Late awakening (>48h after sedation held) was common (78/402) in patients with cardiac arrest in prospective cohort study

--Poor prognostic signs of discontinuous (10-49% suppression) EEG and absent brain stem reflexes were independently associated with late awakening. Use of midazolam also associated with late awakening

--Late awakeners had good functional outcome when compared to early awakeners

DON'T NEUROPROGNOSTIC EARLY (OR IN ED)!

And traditional poor prognostic signs may not be as poor as previously thought!

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Epidemiology of Alpine Skiing Injuries

Mean age of injury 30.3 (range 24 to 35.4 years)

Populations at greatest risk are children and adolescents and possibly adults over 50 (increased risk of tibial plateau fractures)

Sex: Males> females

              Knee injuries, esp to ACL, are higher among females

              Fractures greater in males

Injury location greatest at lower extremity (primarily to knee)

              Primarily sprains to MCL and ACL (increasing incidence)

14% occur to upper extremity and primarily involve the thumb and shoulder

              Skiers thumb – FOOSH with thumb Abducted gripping pole

              Pole is implicated as this injury is rare among snowboarders

The pole acts as a lever to amplify the forced Abduction of the thumb as the outstretched hand hits the ground.

Let go before you hit the ground!!

13% occur to head and neck

The number of all type injuries has decreased over time with advances in equipment and helmet use

Proportion of skiers wearing a helmet exceeds 80%        

However, the number of traumatic fatalities has remained constant

              Accidents involving fatalities exceed the protective capacity of helmets

              Helmets likely decrease risk of mild and moderate head injury

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Acute Disseminated Encephalomyelitis (ADEM) is primarily a pediatric disease and can cause a wide variety of neurologic symptoms. As such, should always be in the differential for pediatric patient presenting with vague neurologic symptoms including altered mental status. It is an immune-mediated, demyelinating disease that can affect any part of the CNS; usually preceding a viral illness or rarely, immunizations.

The average age of onset is 5-8 years of age with no gender predilection. It usually has a prodromal. That includes headache, fever, malaise, back pain etc. Neurological symptoms can vary and may present with ataxia, altered mental status, seizures, focal symptoms, behavioral changes or coma.

MRI is the primary modality to diagnose this condition. Other possible indicators may be mild pleocytosis with lymphocyte predominance, and elevated inflammatory markers such as ESR, CRP. These findings, however, are neither sensitive nor specific.

First-line treatment for ADEM is systemic corticosteroids, typically 20-30 mg/kg of methylprednisolone for 2-5 days, followed by oral prednisone 1-2 mg/kg for 1-2 weeks then 3-6-week taper. For steroid refractory cases, IVIG and plasmapheresis may be considered.

ADEM usually has a favorable long-term prognosis in the majority of patients. However, some may experience residual neurological deficits including ataxia, blindness, clumsiness, etc.

Take home points:

• Always keep ADEM on the differential for any pediatric patient presenting with any neurologic symptoms
• MRI is the diagnostic modality of choice.
• If ADEM diagnosed, start treatment early in conjunction with pediatric neurology.

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Take home naloxone (THN) programs have been expanded to help reduce the opioid overdose-related deaths. A study was done in Australia to characterize a cohort of heroin overdose deaths to examine if there was an opportunity for a bystander to intervene at the time of fatal overdose.

235 heroin-overdose deaths were investigated during a 2 year study period in Victoria, Australia.

• 79% (n=186) of fatality occurred at a private residence
• 83% (n=192) of the decedents were alone at the time of the fatal overdose
• In 34 cases, decedent was with someone else.
  • Half of these witnesses were also significantly impaired at the time of the fatal overdose.
• The opportunity for intervention by a bystander was present in only 19 cases.

Conclusion

1. There was no witness or bystander in majority of overdose deaths.
2. THN alone may only lead to modest reduction in fatal heroin overdose.

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• Intracerebral hemorrhage (ICH) volume is a predictor of mortality and clinical outcome.
• Communicating ICH volume to neurosurgical and neurocritical care consultants can help direct treatment decisions.
• ICH volume can be estimated using the ABC/2 formula:
  • Select the CT slice with the largest area of the hemorrhage (reference slice)
  • A = Measure the largest diameter
  • B = Measure the largest diameter perpendicular to A
  • C = Multiply the number of CT slices with the hemorrhage by the slice thickness
    • Slices with 25-75% of the hematoma volume compared to the reference slice count as 1/2 slice
    • Slices with <25% of the hematoma volume compared to the reference slice do not count

• A recent study by Dsouza et al. found that EM attendings as well as EM trainees were reliable in estimating ICH volume using ABC/2 compared to radiologists.

Bottom Line:  EPs can reliably estimate ICH volume using the ABC/2 formula.  Communicating ICH volume to neurosurgical and neurocritical care consultants can help direct treatment decisions.

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Critically Ill Renal Transplant Patients

• Renal transplant patients are at high risk of critical illness from a variety of etiologies.
• Sepsis is the most common reason for critical illness and ICU admission.  
• Due to their immunosuppression, renal transplant patients are at risk of a multitude of infections.
• Notwithstanding, acute bacterial pyelonephritis of the transplant is the most frequent cuase of sepsis, followed by bacterial pneumonia.
• Be sure to consider these two etiologies when faced with a critically ill, septic renal transplant patient.

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---Early antiviral treatment can shorten the duration of fever and illness symptoms, and may reduce the risk of some complications from influenza.

---Early treatment of hospitalized adult influenza patients with oseltamivir has been reported to reduce death in some observational studies.

---Clinical benefit is greatest when antiviral treatment is administered within 48 hours of influenza illness onset.

Antiviral treatment is recommended for patients with confirmed or suspected influenza who:

---are hospitalized;

---have severe, complicated, or progressive illness; or

---are at higher risk for influenza complications. (See below for in-depth information)

Oral oseltamivir is the recommended antiviral for patients with severe, complicated, or progressive illness who are not hospitalized, and for hospitalized influenza patients.

Treatment:

Doses: Oseltamivir 75 mg twice daily

Renal Impairment Dosing

CrCl >60 mL/minute: No dosage adjustment necessary

CrCl >30 to 60 mL/minute: 30 mg twice daily

CrCl >10 to 30 mL/minute: 30 mg once daily

ESRD undergoing dialysis: 30 mg immediately and then 30 mg after every hemodialysis session

Duration of Treatment:

Recommended duration for antiviral treatment is 5 days for oral oseltamivir. Longer daily dosing can be considered for patients who remain severely ill after 5 days of treatment.

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Dyspnea in the Intubated Patient

• Dyspnea may occur in up to 50% of intubated patients and has been associated with prolonged mechanical ventilation.
• A number of assessment tools are available to detect dyspnea in the intubated patient.
• Regardless of the tool used, once dyspnea is diagnosed, consider the following;
  • When possible, reduce nonrespiratory stimuli of the respiratory drive (i.e., fever, acidosis, anemia)
  • Minimize respiratory impedance (i.e., bronchodilators, thoracentesis for pleural effusion)
  • Optimize ventilator settings (i.e., change modes if applicable, increase inspiratory flow, increase PEEP)
  • Pharmacologic treatment (i.e., opioids, benzodiazepines)

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The European Society of Intensive Care Medicine (ESICM) recently released a review with recommendations from an expert panel for the use of IV fluids in the resuscitation of patients with acute circulatory dysfunction, especially in settings where invasive monitoring methods and ultrasound may not be available.

Points made by the panel include: 

• Circulatory dysfunction should be identified not only by HR and BP, but by other indicators of poor perfusion: altered mentation, decreased urine output, and skin abnormalities (poor skin turgor, mottling, delayed capillary refill)

• The absence of arterial hypotension does not preclude hypovolemia

• The lack of an increase in MAP (especially in patients with decreased vascular tone) does not exclude positive response to IVF

• The purpose of IVF administration is to improve tissue perfusion by increasing cardiac output

• Fluid "loading" as the rapid administration of large volumes of fluid to treat overt hypovolemia, while a fluid "challenge" is a test of fluid responsiveness

• In elderly patients or those with arteriosclerosis or chronic arterial hypertension, a low pulse pressure (e.g. less than 40 mmHg) indicates that stroke volume is low. PP = SBP - DBP

Recommendations from the panel include:

• The early measurement of lactate to incorporate in the assessment of perfusion

• The use of crystalloids as initial resuscitation fluid (unless blood products are indicated)

• When overt hypovolemia is unclear, the use of a fluid challenge of 150-350mL IVF within 15 minutes to help assess fluid responsiveness

• Avoidance of using jugular venous distension alone as a guide for resuscitation

• Avoidance of using acute urine output response alone as a guide for resuscitation, as renal response to fluids can be delayed

• A recommendation against using CVP as a target for resuscitation; if CVP is being measured, a rapid increase with IVF should suggest poor fluid tolerance

• Individualizing fluid resuscitation to the patient's current presentation, underlying comorbidities, and response to fluids

Bottom Line: Utilize all the information you have about your patient to determine whether or not they require IVF, and reevaluate their physical and biochemical (lactate) response to fluids to ensure appropriate IVF administration and avoid volume overload. 

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Taking a double-dose of a single medication is presumed to be safe in most cases. However, there is limited data to support this assumption.

A retrospective study of the California Poison Control System was performed to assess adverse effects of taking double dose of a single medication. During a 10-year period, 876 cases of double-dose ingestion of single medication were identified.

Adverse effects were rare (12 cases). However, medication classes that were involved in severe adverse effects included: 

1. Propafenone: ventricular tachycardia and syncope
2. Beta blockers (BB): bradycardia and hypotension
3. Calcium channel blockers (CCB): bradycardia and hypotension
4. Bupropion: seizure 
5. Tramadol: ventricular tachycardia

Conclusion:

• Adverse effect from double dosing is rare.
• Cardiovascular collapse can occur with BB and CCB
• Seizure can occur with tramadol and bupropion.

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A previous pearl discussed medication-overuse headache (MOH).

MOH is also known as analgesic rebound headache, drug-induced headache or medication-misuse headache.

It is defined as headache… occurring on 15** or more days per month in a patient with a preexisting headache disorder who has been overusing one or more acute treatment drugs for headache with symptoms for three or more months.

The diagnosis is clinical, and requires a hx of chronic daily headache with analgesic use more than 2-3d per week.

The diagnosis of MOH is supported if headache frequency increases in response to increasing medication use, and/or improves when the overused medication is withdrawn.

The headache may improve transiently with analgesics and returns as the medication wears off. The clinical improvement after wash out is not rapid however, patients may undergo a period where their headaches will get worse. This period could last in the order of a few months in some cases.

The meds can be dc’d cold turkey or tapered depending on clinical scenario.

Greatest in middle aged persons. The prevalence rages from 1% to 2% with a 3:1 female to male ratio.

Migraine is the most common associated primary headache disorder.

** Each medication class has a specific threshold.

Triptans, ergot alkaloids, combination analgesics, or opioids on ten or more days per month constitute medication overuse.

Use of simple analgesics, including aspirin, acetaminophen and NSAIDS on 15 or more days per month constitutes medication overuse. 

Caffeine intake of more than 200mg per day increases the risk of MOH.

Consider MOH in patients in the appropriate clinical scenario as sometimes doing less is more!

Historically uncuffed endotracheal tubes were used in children under the age of 8 years due to concerns for tracheal stenosis.  Advances in medicine and monitoring capabilities have resulted in this thinking becoming obsolete.  Research is being conducted that is showing the noninferiority of cuffed tubes compared to uncuffed tubes.  Multiple other studies are looking into the advantages of cuffed tubes compared to uncuffed tubes.

The referenced study is a meta-analysis of 6 studies which compared cuffed to uncuffed endotracheal tubes in pediatrics.  The pooled analysis showed that more patients needed tube changes when they initially had uncuffed tubes placed.  There was no difference in intubation duration, reintubation occurrence, post extubation stridor, or racemic epinephrine use between cuffed and uncuffed tubes.

Bottom line: There is no difference in the complication rate between cuffed and uncuffed endotracheal tubes, but uncuffed endotracheal tubes did need to be changed more frequently.

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Selective serotonin reuptake inhibitors are the most common anti-depressant used today. However, the use bupropion in adolescents is increasing due the belief that it has fewer side effects than TCAs.

Using the National Poison Data System (2013 – 2016), the adverse effects of bupropion were compared to TCA in adolescents (13 – 19 years old) with a history of overdose (self harm). 

Common clinical effects were:

TCA:  n=1496; Bupropion: n=2257

Conclusion:

Bupropion overdose results in significant adverse effects in overdose; however, death is relatively rare.

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• Lumbar punctures (LPs) are a common ED procedure with variable reported success rates.
• A recent systematic review and meta-analysis looked at 12 studies comprising 957 adult and pediatric patients comparing pre-procedural ultrasound-assisted LPs with traditional landmark-based technique.
  • Some studies utilized ultrasound-assistance in all LPs, others selected patients who were anticipated to be difficult LPs.
  • No studies assessed dynamic ultrasound-guided LPs.
• Overall, ultrasound-assisted LP was 90.0% successful compared with landmark-based LP that was 81.4% successful (OR 2.22, 95% CI = 1.03 - 4.77).
• Ultrasound-assisted LP was also associated with reduced rate of traumatic LPs, shorter time to successful LP, and reduced patient pain scores.

Bottom Line: Consider using pre-procedural ultrasound-assistance for all lumbar punctures.

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Noninvasive Ventilation in De-Novo Respiratory Failure

• Noninvasive ventilation (NIV) is a primary therapy for patients with acute hypercapnic respiratory failure, especially those with an acute COPD exacerbation.
• Notwithstanding its benefits in COPD and acute cardiogenic pulmonary edema, NIV should be used cautiously in patients with "de-novo" respiratory failure.
• Many patients with de-novo respiratory failure will meet criteria for ARDS and have a high rate of intubation (30% - 60%).
• The use of NIV with delayed intubation in this patient population has been associated with increased mortality. 

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Retrospective chart review at a headache clinic seeing adolescent concussion patients

70.1% met criteria for probable medication-overuse headache

Once culprit over the counter medications (NSAIDs, acetaminophen) were discontinued,

68.5% of patients reported return to their preinjury headache status

Take home:  Excessive use of OTC analgesics post concussion may contribute to chronic post-traumatic headaches

If you suspect medication overuse, consider analgesic detoxification

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