2020 Year in Review (Jimenez, Green 2/24/2021)

Great thanks to Dr. Douglas Jimenez and Dr. Cherie Green for their Grand Rounds 2020 Year in Review. Much of the presentation focused on-- you guessed it-- COVID (that is basically what ALL our lives revolve around these days), with select bonus points on a few other hot topics. Dr. DJ covered the latest and greatest on COVID in OB and Dr. Green did a potpourri of COVID in kids. 

The COVID literature is evolving literally day by day, so please take this summary as a point in time update. Our understanding of the disease will continue to evolve as we get more data/studies/literature on these topics. For a video recording of this presentation, click here: VIDEO.

Here are my summary points from this presentation:

COVID OB Management in 2020:

• Pregnant women appear to be at higher risk for severe COVID illness and death
• 5-6% of pregnant women with COVID are hospitalized
• 3x risk ICU, 2.9x risk intubation, 1.7x risk of death

• Pregnant women with severe/critical COVID disease also appear to be at increased risk for preterm birth and pregnancy loss
• 10-25% preterm delivery (induced + spontaneous)
• 60% preterm delivery in critical illness
• Per SMFM, a history of COVID disease is NOT itself an indication for antenatal testing
• use routine indications for antenatal testing
• however, a 32 week growth ultrasound may be considered
• Is COVID an indication for delivery?
• asymptomatic/mild infection: COVID is not an indication for delivery, though can consider delivery if >39 weeks
• severe/critical illness: it is reasonable to consider delivery but mechanical ventilation alone is not an indication for delivery
• if EGA< 32 weeks and considering delivery, also consider proning, ECMO, etc
• Is COVID vaccination recommended in pregnancy?
• Due to lack of data in vaccine trials, the WHO has been "lukewarm" about recommending COVID vaccine, recently adjusting their recommendation to recommend vaccinating women at high risk (e.g. healthcare workers) and those with comorbidities that put them aat increase risk for severe illness (e.g. diabetes, obesity).
• However, it is important to note that the Maternal Immunizations Task Force (which includes many large and reputable organizations including: ACOG, AAFP, IDSA, AAFP) specifically recommend that COVID-19 vaccine be made available to all pregnant women
• they say it is unethical to not offer vaccine knowing that pregnancy is a risk factor for more severe COVID illness
• this should be a shared decision-making conversation with provider on risk vs, lack of safety data
• What about Breastfeeding and COVID?
• CDC recommends ALL women with active COVID continue to breastfeed-- no evidence of COVID in breast milk, benefits>>risks
• should use face mask and hand hygiene with every feed
• Labor support and COVID
• Policies surrounding limitation of support people in labor disproportionately harm women of low SES and women of color, who are also disproportionately affected by COVID-19
• less labor support--> more operative delivery, longer labors, etc
• We should be mindful of these policies and do our best to weigh risks/benefits in our advocacy work

Bonus Pearl: Alcohol in pregnancy. Dr. DJ reviewed a paper from Australia  (Association of Perinatal Alcohol Exposure with Psychological, Behavioral, and Neurodevelopmental Outcomes in Children from the ABCD Study, American Journal of Psychiatry  2020), which found a dose-dependent correlation between ANY alcohol use in pregnancy and psychological/emotional problems and behavioral problems. 

• 25% increased likelihood of an ADHD in children exposed to heavier levels of alcohol (approximately 36 drinks) in the first 6-7 weeks of pregnancy.
• Heavier alcohol use during early pregnancy also associated with rule breaking behavior and aggression, 30% higher risk of the child being diagnosed with oppositional defiant disorder

COVID + kids 2020:

Dr. Green reviewed several studies on the impact of COVID on our children. Here are her pearls:

• 2020 study out of China, 123,000 children looking at myopic changes with a 5 month lock down
• in children ages 6-8 years, significant number of children had a clinically significant myopic shift (-0.3 diopters) with higher prevalence of myopia in children compared to previous years
• this was not true in older children (ages 9-12)
• conclusion: home confinement seemed to have a significant effect on vision and myopia rates in children ages 6-8, perhaps because this is a more critical developmental period for this problem
• Clinical pearl: every 20 minutes, have children look up and way from the screen for at least 20 seconds, 20 feet away
• Mental health in children during the Pandemic
• Clark County, Nevada: 19 deaths by suicide
• Riley Hospital, Philadelphia: 250% increase in hospitalization for childhood suicide attempts
• CHO: double rate of childhood suicide attempts compared to 1 year ago
• CDC reports increase in mental health ED visits, sustained since March 2020 (see image)
• 25% increase in children 5-11, 31% in children 12-17, compared to the same period one year prior
• Clinical pearl: Ask ALL children how there mental health is doing during the pandemic. Particularly for teens, consider the use of APPS: including CALM, headspace, COVID coach
• 
• The Safety of School Reopening 

• SARS-CoV-2 infection and transmission in educational settings: a prospective, cross-sectional analysis of infection clusters and outbreaks in England Ismail et al, Lancet December

• prospective study, strict infection control precautions, small groups, low community prevalence
• 1,000,000 students, 500K staff--> 343 total cases of COVID (130 in children, 213 in staff)
• 55 total outbreaks (outbreak defined as more than 1 person, most involved just 2), probable staff to staff in 26 of those outbreaks
• no children hospitalized, 3 adults hospitalized, 1 adult died (contracted from home)
• Summary: SARS-CoV-2 infections and outbreaks were uncommon in educational settings during the summer half-term in England. The strong association with regional COVID-19 incidence emphasises the importance of controlling community transmission to protect educational settings. Interventions should focus on reducing transmission in and among staff”

• Incidence and Secondary Transmission of SARS-CoV-2 Infections in Schools

  Zimmerman et al, Pediatrics 2021
• 11 districts in North Carolina, 100K students x 9 weeks
• 32 additional cases of COVID via school transmission
• No instances of child to adult transmission
• Summary:

• In the first 9 weeks of in-person instruction in NC schools, secondary transmission of SARS-CoV-2 was extremely low overall, and only involved staff to staff transmission. “Our data support the concept that schools can stay open safely in communities with widespread community transmission.”

With mitigation in place (distancing, handwashing, ventilation) schools do not appear to be contributing widely to the spread of COVID in the community. They CAN be reopened safely and prevent some of the unfortunate other unsafe conditions for children, particularly our most vulnerable children.

Interrupting Racial Trauma: Strategies & Tools to Assist Health Care Professionals to Do No Harm (Washington, 2/17/2021)

A HUGE thanks to Dr. Sharon Washington for her wisdom on interrupting bias in the health care setting. Engaging in anti-racism is hard work. We know that every institution in this nation is struggling now to confront the recognition that race and racism are a fundamental part of who we are as a nation, as a society, and as a community. Healthcare is no different. I will add a summary of this Grand Rounds in the near future. Better yet: watch it yourself here: https://youtu.be/YpjNkCTNpxY

Benzodiazepine-Sparing Alcohol Withdrawal (Maldonado, 2/10/2021)

Great thanks to Dr. Jose Maldonado, a Stanford psychiatrist and neuropsychiatrist, who literally wrote the benzodiazepine-sparing alcohol withdrawal protocols that we have been utilizing at SSRRH for the last few years. He gave us a deep dive into the science behind them this week! If you want to see the whole presentation, it is archived here: VIDEO: Benzo Sparing Alcohol Withdrawal 

For those of you who prefer the written word, here is Dr. Maldonado's paper, and for those who prefer an abbreviated version, here are my notes from Grand Rounds:

Alcohol Use Disorder is extremely common in our society, particularly among hospitalized patients: 20-42%of hospitalized medical patients; ~7% are identified by physician. Check out these numbers:

• 40% of ED patients
• 43-81% surgical and head and neck patients
• 42% of hospitalized veterans 
• 59-67% of trauma patients
• up to 44% elderly patients admitted to acute geriatric units

Remember that legal driving limit is a blood alcohol concentration (BAC) of 0.08. Alcohol follows zero order kinetic metabolism, which means there is nothing we can do to slow down or speed up its rate of metabolism.  Ethanol is metabolized at rate of 0.015% per hour,which means a  person with BAC of 0.15 (twice the legal driving limit) will have no measurable alcohol in the bloodstream after 10 hours. 

Alcohol Withdrawal Syndromes

This is something I did not really know before this presentation: alcohol withdrawal CAN present even if BAC is still quite elevated. In fact, signs and symptoms of withdrawal occur once a person's BAC drops by 30% from their usual level; this means that you don't have to be at a BAC of zero to have symptoms of alcohol withdrawal. In fact, you can be in DTs even with an extremely elevated BAC, if it is just lower than where you normally live.

Here is another pearl: 80% of patients withdrawing from alcohol do NOT require aggressive medical treatment; supportive management is enough. If we treat everyone who walks through the door for alcohol withdrawal, we will definitely over treat--> leading to respiratory depression, toxicity, falls, oversedation, etc.

There are FOUR unique alcohol withdrawal syndromes: 2 are dangerous/complicated, 2 are not

1. Uncomplicated Alcohol Withdrawal ("The Shakes")
• 80% of all patients
• tremor, usually fine (but can be coarse)
• GI distress, anxiety, difficulty sleeping/insomnia, violent and unpleasant dreams, mild sx of autonomic instability
• sx decrease usually by day 5, more severe symptoms last 10-14 days
2. Alcohol Withdrawal Seizures ("Rum Fits")--> complicated 
• 5-15% of all patients
• peaks quite early: 12-48 hours (much earlier than DTs)\
• the greater the amount of alcohol consumed, the greater the risk of seizure
3. Alcoholic Hallucinosis  ("The Horrors")
• up to 30% of all patients
• onset: ~8 hours, peak 24-96 hours
• related to length and amount of alcohol exposure
• auditory, visual, tactile hallucinations in context of CLEAR sensorium, stable VS
4. Delirium Tremens ("DTs")--> complicated
• ~5% of all patients
• peak can be relatively late, up to 7 days after stopping alcohol
• "autonomic storm"
• 1% mortality in healthy person, but can be as high as 20% if elderly and multiple medical issues

What is the problem with benzodiazepines?  Well, you and I know that there are too many things to count. . . here are a few:

1. Benzos have serious abuse liability; plus there is 29-76% concurrent alcohol and benzo use
2. Benzo use may increase craving, early relapse to alcohol use, and increased alcohol consumption
3. Benzos are CNS depressants and really prolong withdrawal rather than treat it
4. Benzos cause psychomotor retardation, cognitive blunting, ataxia, poor balance, and decreased mobility
5. Benzos disrupt circadian rhythms of melatonin release, interfering with sleep
6. Benzos disrupt thalamic gating
7. Benzos are associated with an increased risk of delirium (40% of the time)

The Neurotransmitter-imbalances of Alcohol Withdrawal

Alcohol withdrawal is a complicated cascade of neurotransmitter imbalances involving all kinds of brain chemistry (this takes me way back to my neuroscience degree from undergrad). For the purposes of the algorithm, key imbalances include: excess of norepinephrine (NE), glutamate, dopamine, as well as a defective GABA-ergic system

The very imbalances of these neurotransmitters is what is being addressed in the benzo-sparing protocol, aimed at evening things out.

1) Alpha 2 agonists are the basis of the benzo sparing protocol: taking you way back to pharmacology 101, the alpha 2 agonists work at the presynaptic receptor, preventing the release of massive amounts of NE and Glutamate that occurs in alcohol withdrawal--> this, in essence treats, rather than masks (in contrast, Beta blockers mask alcohol withdrawal (post synaptic), but patient will still seize)

There are three alpha-2 agonists (in order of efficacy)

• clonidine: cheap, easy, readily available, comes in PO/IV/patch
• dexmedetomidine (precedex): highly selective alpha 2>alpha 1: offers more anxiolysis, less hypotension and bradycardia. BUT it is only IV, and has to be administered in ICU/monitored bed (there are not great papers, but lots of good anecdotal evidence, intensivists use it all the time at SSRRH)
• guanfacine: more highly selective than even dexmedetomidine, but has long half life (takes a bit to kick in)

There are at least 11 studies showing a benefit of alpha-2 agonists OVER  benzos (better in terms of withdrawal, anxiety, agitation, progression to DTs), Dr. Maldonado says these agents overall are about 3x better than benzos.

2) The other major component of the benzo-sparing protocol are the Antiglutamatergic agents/calcium channel modulators. These include carbamazepine, valproic acid (VPA), gabapentin, and pregabalin to name a few. Dr. Maldonado prefers pregabalin>gabapentin>VPA.

• 13 studies: head to head, cbz, VPA are equal to or superior to benzos without all the problems benzos have
• VPA (available PO/IV)
• Gabapentin multiple studies showing equal to or superior to benzo
• Pregabalin: same mechanism of action, but gabapentin only absorbed in small intestine, more gabapentin you give, the less you absorb. Pregabalin absorbed throughout entire GI tract, peak plasma concentration 1 hour (compared to 3-4 for gabapentin),

How do we distinguish which patients who will go through withdrawal need treatment?

To distinguish those 80% who only need supportive care from those who needs medical management, you can use the PAWSS Score, close to sens 100%, spec 100% to predict alcohol withdrawal

• PAWSS<4, pt might withdraw but will not have complicated withdrawal
• PAWSS>4: pt WILL have severe or complicated withdrawal
• if already withdrawing, treat
• if not, ppx arm

Summary of Stanford Benzo Sparing Protocol

A. Alpha 1 agonist: 0.1mg clonidine patch x 2 (#1 removed day 4, #2 removed day 7) PLUS 0.1mg PO/IV q 8 hours x 3 doses 
B. IF vital signs unable to tolerate alpha 2 effect OR patient has excess anxiety--> you can instead use high dose gabapentin (1200mg loading, 800mg TID w/taper) OR high dose pregabalin 150 mg loading (see here for protocol) OR VPA 250mg PO/IV BID + 500mg QHS

• IF patients at extremely high risk for AWS (PASS>7 or BAL>300 on admission) USE both A+B
• For adjunct medication: melatonin 10 mg PO qhs, hydroxyzine prn anxiety, doxylamine prn insomnia
• benzos (PO lorazepam) should only be used if high breakthrough sx despite adequate treatment with A+ B (e.g. CIWA>15 or >20) 

Random pearls:

• Electrolyte abnormalities are particularly common in patients with alcohol use disorder and alcohol withdrawal: watch K+ (QT prolongation), Mg
• of note, hypomagnesemia is #1 electrolyte abnormality that predicts seizure in patients with withdrawal
• Thiamine deficiency is also endemic patients with alcohol use disorder: all patients with AUD should get thiamine 500 mg IV/PO/Im TID x 3-5 days
• Dr Maldonado says that they do discharge folks from their ER to home on these regimens with outpatient follow-up

In summary, per Dr. Maldonado, using a benzo-sparing protocol is safe and effective, decreases the risk of delirium as well as other adverse effects of benzodiazepines, decreases LOS, and ultimately hopefully helps the patient in the long-run. Go forth and get folks off their alcohol.

Psychiatric Emergencies in the Hospital (Kostick, 2/3/2021)

Many thanks to Dr. Talia Kostick for an excellent presentation on Psychiatric Emergencies in the Hospital: etiologies, clinical presentations, and treatments. She also included a bit on medical-decision making capacity and involuntary hospitalization-- issues we confront quite frequently in the hospital.

Dr. Kostick took us through 4 cases of patients we cared for at SSRRH with these Psychiatric Emergencies. If you want to see the recording, it is available here: https://youtu.be/Tr0I22vNuiY

Psychiatric emergency: when a psychiatric condition causes an imminent threat to the life of the patient or the possibility of permanent neurologic or physiologic damage. These include:  

• Serotonin Syndrome
• Catatonia
• NMS 
• Anticholinergic Toxicity
• Suicidal Intent (not covered her)

Serotonin syndrome: potentially fatal drug induced condition, caused by too much serotonin in the synapses in the brain. Patients present with a combination of neuromuscular, autonomic, and mental status symptoms

• s/sx: clonus, tremor, sweating, tachycardia, restlessness, confusion, delirium
• meds common cause: MAOi, Antidepressants (SSRI, SNRI, TCAs), opiates, natural health products. Worse in combination, high dose
• treatment: 
• discontinue any/all serotonergic drugs
• supportive care (esmolol, nitroprusside)
• sedation with benzos
• paralytics and intubation for hyperthermia
• in serious cases serotonin antagonists

Catatonia: displaying 3 or more of 12 psychomotor features (see table)

• usually diagnosed inpatient
• majority in depression, can occur up to 35% of patients with schizophrenia
• s/sx: immobility, mutism, withdrawal and refusal to eat, rigidity, echolalia (see table)
• treatment: benzos! (1-2mg of SL, IV or IM lorazepam--> repeat in 3 hours), also ECT effective
• more likely to respond if bipolar, less likely if schizophrenia

Neuroleptic Malignant Syndrome (NMS): alteration in the autonomic and somatic nervous system caused by decreases in function of the central dopamine system

• 10% mortality (more fatal than serotonin syndrome)
• incidence 0.01-0.2% of all patients treated with antipsychotics
• greatest risk in high dose first generation psychotics (e.g. haldol)
• diagnosis of exclusion: 1) exposed to dopamine antagonist 2) mental status change 3) "lead pipe muscle rigidity", autonomic instability (tachy, tachypnea, hypertension), hyperthermia w/diaphoresis, elevated CK
• tx: stop dopamine antagonist, can add dopamine agonist ( bromocriptine, amantadine, levodopa), decreased noradrenergic activity (with benzos)

Anticholinergic Toxicity: 

• blind as a bat, hot as a desert, mad as a hatter, dry as a bone, red as a beet (see image)
• LOTS of meds with anticholinergic effects: antiemetics, corticosteroids, analgesic, steroids
• Tx: stop the med, provide supportive care, in severe cases (cardiac effects), can administer physostigmine

Capacity Assessment: 4 parts

1) Comprehension: Can patient express an understanding of current medical conditions, risks/benefits of proposed treatments?

2) Expression of a choice: Does the patient have the ability to state and explain their decision?

3) Appreciation: Is the patient able to appreciate the consequences of their decision?

4) Depression/delusions/intoxication: if any of these affecting decisions, do not have capacity