52 y/o male with HTN, hyperlipidemia, chronic back pain, and recent depression came back from a walk and per family was ataxic, dysarthric and confused, so his family drove him to the ED. On the way, he began vomiting repeatedly and became increasing obtunded. As he entered the ED went into apparent cardiovascular and respiratory collapse. Given 2mg of Naloxone without response and intubated by RSI for further evaluation.
Vitals on arrival in the ED: Temp: 36, RR:-no spontaneous breaths noted after entering the ED O2: 88% on bag valve mask, HR: 68 BP: 88/64. Glucose 104. GCS 3 (non verbal, no motor movement, pupils 2mm and fixed). No corneal or occulacephalic reflexes noted, no cough or gag elicited. All extremities were flaccid and areflexic. EKG show sinus rhythm, no obvious conduction abnormalities.
Medication hx: Simvastatin 40 mg daily, amlodipine 10 mg daily, Baclofen 20 mg TID, Vicodin 5-300 1 tablet q6 hrs
Labs: ETOH: 150. CBC, lactic acid, chemistry, venous blood gas (on ventilator), CPK, LFT’s, troponin asa, acetaminophen, UA, UDS all WNL
Imaging: CTA pan scan negative except for mild aspiration in the R lung base.
So what happened…..?
What is it?
Baclofen is a synthetic derivative of the naturally occurring inhibitory neurotransmitter GABA.
Acts principally on the GABA-B receptor at the spinal level and reduce the post-synaptic potentials along motor neurons, thus relaxing the skeletal muscles.
Baclofen is primarily used for the treatment of spastic movement disorders and now more ubiquitously for the treatment of chronic back pain.
How is it given?
Oral: Until the past 10 years, the primary method of administration of Baclofen was oral.
- Peak concentration in 2 hours and half life of 3.5hours
- Dosage 40-80mg daily dosed q8 hrs
- Centrally acting but crosses the blood brain barrier ineffectively, limiting its bioavailability
- Very low toxic range with severe toxicity from oral baclofen, necessitating ICU level care occurring fairly consistently with baclofen overdoses of over 200mg (a 3 day supply for most people)
Intrathecal: Intrathecal baclofen is administered through the implantation of a pump subcutaneously with a catheter from the pump inserted directly into the CSF fluid.
- Dosage: 90 mcg to 800 mcg daily
- Intrathecal baclofen allows for 4x the amount of baclofen to be delivered to the spinal cord with just 1% of the oral dose.
Intrathecal Baclofen Pumps: The pump is surgically implanted under the skin in the abdomen and the catheter is tunneled under the skin and inserted into the intrathecal space usually between the 1st and 2nd lumbar vertebrae.
Currently SynchroMed is the only pump currently being used in the US for intrathecal baclofen, hydromorphone and morphine
- The catheter holds 3-4ml
- The reservoir holds 20-40ml
- Pump battery lasts for 5-7 years
Baclofen has the potential for both overdose and withdrawal, which can both present with a wide array of symptoms.
Most commonly include CNS depression, lethargy, somnolence, hallucinations, agitation, mydriasis/miosis, nausea and vomiting
Severe toxicity is associated with bradycardia, hypotension (more common) or hypertension, respiratory failure, hypothermia, seizures, coma and death.
Rarely, rhabdomyolysis and conduction disturbances may occur
Oral Baclofen overdoses:
- Usually intentional overdoses-either for recreational or self harm
Intrathecal baclofen overdoses:
- Wrong dose is manually programmed into the pump
- Wrong concentration is placed in the pump
- Wrong bolus is given when starting the pump
- Wrong port is accessed or wrong port filled
Patients are usually treated by supportive methods only.
In severe overdoses, this often means supporting blood pressure with fluids and pressors and often-mechanical ventilation for respiratory failure until drug toxicity subsides.
Generally overdose symptoms will resolve in approximately 24-48 hours
For Intrathecal baclofen overdoses:
Most are correctable by emptying the pump reservoir:
- Turn off pump-programmer (need external device programmer to do this)
- Empty reservoir: Use a 22 gauge needle to stick the middle of the pump and pull out all the drug
Remove the CSF- Use a 24-25 gauge needle to stick the side port and aspirate 30-100 ml of CSF
In severe cases performing a lumbar puncture to reduce circulating baclofen in the CSF while performing all normal supportive strategies (small case reports- this involves replacing entire circulating volume of CSF with saline and has been used successfully in a few cases of massive overdose)
Similar to withdrawal from alcohol or benzodiazepines, with the loss of gaba-mediated inhibition: hyper metabolic states, spasticity/rigidity, hallucinations/seizures, tachycardia, hyperthermia, and hypertension are more commonly observed.
Mild: pruritus, agitation, diaphoresis and increased tone
Moderate: fever, tachycardia, spontaneous clonus and painful muscle spasm
Severe: worsening of above along with seizures, delirium, hallucinations, rhabdomyolysis and death.
Remember the mnemonic, "ITCHY, TWITCHY, BITCHY."
Causes of Withdrawal
Oral Baclofen Withdrawal:
- Oral Baclofen withdrawal can occur when a person is abruptly stops taking baclofen or weans off to fast.
- Of note oral baclofen diffuses through the blood brain barrier deep into the brain whereas- intrathecal baclofen stays almost exclusively in the CSF with a penetration of only approximately 1-2 inches into the brain. Therefore, a person who is being switched to intrathecal baclofen must still be tapered off their oral baclofen or they will withdraw.
Intrathecal Baclofen Withdrawal:
- Intrathecal Pump Malfunction
- Intrinsic pump malfunction is exceedingly rare.
- Pocket Refill
- Rather than an overdose this results in acute withdrawal as intrathecal dosing is 1/100th of oral dosing/subcutaneous dosing.
- Battery failure
- Expected to die at 84 months.
- Will alarm 3 months prior.
Medication Changes or interactions:
- SSRI’s especially known for decreasing effect
Catheter malfunctions: (kink, micro/macroleaks, scarring, migration)
- Most common cause of pump failure
- KUB and AP/lateral spine first step to look for catheter fracture or migration
Oral Baclofen withdrawal is usually easily treatable by restarting baclofen and introducing a slow tapered wean if discontinuation is desired.
Intrathecal Baclofen Withdrawal presents more of a challenge in both recognition and treatment. It can be tricky to recognize baclofen withdrawal as it often masquerades as sepsis (ex-tachycardia, hyperthermia, altered mental status). It is important to recognize that many of these patients have severe spasticity and may have limited verbalization skills. Often they come from long term care facilities without much information, along with the fact that many times the baclofen will not be listed on their daily facility medication list, making it extremely important to look for a pump every time.
Recognizing that a patient’s symptoms may be secondary to intrathecal baclofen and interrogating the pump and obtaining pump series imaging to evaluate for catheter related malfunctions is a key first step
Essentially intrathecal baclofen withdrawal requires intrathecal baclofen. The key is finding the reason for the withdrawal and fixing the primary cause. Everything else is a temporizing measure.
To help with symptoms while attempting to fix the primary cause of pump failure treatment can include:
- High Dose Oral Baclofen
- Treating intrathecal baclofen withdrawal with oral baclofen is often unsuccessful as the vast difference in bioavailability of oral doses and intrathecal doses.
- Benzodiazepine treatment
- Propofol low dose
- Experimentation with Dexamedetomidine and cyproheptadine
- CSF infusion of Baclofen
So what happened to our patient?
After approximately 18 hours intubated, our patient began waking up, became agitated and self-extubated himself. He admitted to taking approximately 900 mg of baclofen in a suicide attempt the day of admission. He was discharged to inpatient psychiatry without any further medical sequela on hospital day 3.
Take Home Points
- Overdose: variable presentation, CNS depression is often involved, good supportive care is key.
- Withdrawal: variable presentation, Itchy/twitchy/bitchy. Will have increased muscle tone from baseline.
- Always remember the pump is there.
- Overdose: For intrathecal overdose-2 ports from which you can draw drug and CSF back out.
- Withdrawal: Look for the cause and treat supportively with oral baclofen, benzos, and propofol.
Faculty Reviewer: Dr. Kristina McAteer
Image 1: “Spasticity2” by Bill Connelly- Own Work
Image 2: http://www.gablofen.com/patients/intrathecal-baclofen-therapy
Image 3: http://www.ajnr.org/content/32/7/1158
Image 4: http://www.rch.org.au/kidsinfo/fact_sheets/Intrathecal_baclofen_3_the_ITB_pump/
Image 5: http://www.cliparthut.com/clip-arts/175/people-clip-art-175256.gif
Image 6: https://emcow.files.wordpress.com/2014/01/baclofen-3.jpg
Welcome to the first episode of AEM Education and Training, a podcast collaboration between the Academic Emergency Medicine E&T Journal and Brown Emergency Medicine. Each quarter, we'll give you digital open access to an AEM E&T Article or Article in Press, with an author interview podcast and links to curated supportive educational materials for EM learners and medical educators.
Find previous AEM Early Access podcasts and suscribe to this series on iTunes here.
Discussing open access article (with link to full text):
Emergency Medicine Morbidity and Mortality Conference and Culture of Safety: The Resident Perspective. Kathleen Wittels MD, Emily Aaronson MD et al. AEM Education and Training 2017;1:191–199.
LISTEN NOW: Lead Author Interview with Dr. Kathleen Wittels, M.D.
We discuss the evolution of Morbidity and Mortality Conference from its tradition of "blame and shame" to its current ideal role in emergency medicine training and a culture of safety. Dr. Wittels and her colleagues previously published data on residency program directors' perceptions of M&M at their programs -- but what do residents think?
Kathleen Wittels, MD
Assistant Professor of Emergency Medicine, Harvard Medical School
OBJECTIVE: Morbidity and mortality conference (M&M) is an Accreditation Council for Graduate Medical Education (ACGME) requirement for emergency medicine residents. This study aimed to survey the attitudes of EM residents towards M&M conference and to characterize the prevalence of elements of EM M&M conferences that foster a strong "culture of safety".
METHODS: Emergency medicine residents at 33 programs across the United States were surveyed using questions adapted from a previously tested survey of EM program directors and the Agency for Healthcare Research and Quality (AHRQ) Culture of Safety Survey.
RESULTS: The survey response rate was 80.3% (1,002/1,248). A total of 60.3% (601/997) of residents had not submitted a case of theirs to M&M in the past year. A total of 7.6% (73/954) reported that issues raised at M&M always led to change while 88.3% (842/954) reported that they sometimes did and 4.1% (39/954) reported that they never did. A total of 56.2% (536/954) responded that changes made due to M&M were reported back to the residents. Of residents who had cases presented at M&M, 24.2% (130/538) responded that there was regular debriefing, 65.2% (351/538) responded that there was not, and 10.6% (57/578) were unsure. A total of 10.2% (101/988) of respondents agreed that M&M was punitive, 17.4% were neutral (172/988), and 72.4% (715/988) disagreed. A total of 18.0% (178/987) of residents agreed that they felt pressure to order unnecessary tests because of M&M, 22.3% (220/987) were neutral, and 59.6% (589/987) disagreed. A total of 87.4% (862/986) felt that M&M was a valuable educational didactic session, and 78.3% (766/978) believed that M&M contributes to a culture of safety in their institution.
CONCLUSIONS: While most residents believe that M&M is a valuable didactic session and contributes to institutional culture of safety, there are opportunities to improve by communicating changes made in response to M&M, debriefing residents who have had cases presented, and taking steps to make M&M not feel punitive to some residents.
To Err is Human: Building a Safer Health System. Institute of Medicine (US) Committee on Quality of Health Care in America; Kohn LT, Corrigan JM, Donaldson MS, editors. Washington (DC): National Academies Press (US); 2000.
Morbidity and Mortality Conference in Emergency Medicine Residencies and the Culture of Safety. Emily L Aronson, MD, Kathleen Wittels, MD, et al. West J Emerg Med. 2015 Nov; 16(6): 810–817.
Presentation and History
A 17-year-old female with a history of depression and eating disorder presents to the emergency department after an intentional overdose of citalopram, sertraline and ibuprofen.
Initial work up
On arrival, the patient is noted to have a blood pressure 132/57 mmHg, tachycardic with a heart rate of 128 beats per minute, afebrile with a normal respiratory rate and an oxygen saturation of >95% on room air. On physical examination, the patient was initially alert and oriented to person, place and time. Her lungs were clear to auscultation bilaterally. Cardiac exam was tachycardic and regular without murmur, rub or gallop. The abdomen was soft, non-tender and non-distended with hyperactive bowel sounds. Her neurologic exam was notable for hyperreflexia and 5-6 beats of inducible clonus in the lower extremities as well as a mild resting tremor. EKG demonstrated sinus tachycardia with normal axis and intervals. Bedside glucose was 90. The patient’s acetaminophen and salicylate levels were <10 and <2.5, respectively. The metabolic panel was notable for potassium of 3.3. The LFTs and CBC were within normal limits.
ED course and disposition
15 minutes into her ED stay, the patient had a generalized tonic-clonic seizure lasting approximately 30 seconds. She received lorazepam 2mg intravenous (IV) and was moved to the resuscitation bay. She received repeated doses of benzodiazepines along with aggressive fluid resuscitation and was admitted to the pediatric intensive care unit.
Serotonin syndrome is a life-threatening condition due to increased serotonergic activity in the central nervous system. The syndrome can occur through accidental overdose, deliberate self-poisoning, or even therapeutic medication use. The classic triad of mental status changes, autonomic hyperactivity and neuromuscular abnormalities is not always seen, and the presentation can be subtle.
Classic neuromuscular findings include hyperreflexia and muscular rigidity greater in the lower extremities than in the upper extremities, as well as clonus. Roving eye movements known as “ocular clonus” can also be seen.
Complications of serotonin syndrome include cardiac dysrhythmias, seizures, metabolic acidosis, rhabdomyolysis, and severe hyperthermia resulting in end organ failure and disseminated intravascular coagulation.
Treatment is largely supportive including respiratory support, IV fluids and benzodiazepines.
Adjunctive therapies include GI decontamination with activated charcoal if ingestion is within two hours, and cyproheptadine. Cyproheptadine is a first-generation anti-histamine that also has anti-serotonergic properties, and should be considered if supportive measures fail. Caution must be exercised as this medication is only available in PO formulation and would require NG tube placement in the obtunded patient. Downsides of cyproheptadine include exacerbating hypotension, so it should not be used on patients with profound autonomic instability as can be seen in some cases of serotonin syndrome.
Supportive care also includes treating patients who have a temperature of greater than 41.1C (106F) with immediate intubation and paralysis with a non-depolarizing neuromuscular blocking agent (e.g. rocuronium or vecuronium). Active cooling measures should also be initiated at this point.
Citalopram and escitalopram are worth special mention as these two SSRIs can cause significant widening of the QRS and QTc interval, which can degenerate into torsades de pointes up to 12 hours after ingestion. Thus, patients who have EKG changes or persistent sinus tachycardia should be admitted to a critical care setting and observed on telemetry with serial EKGs for at least this duration.
The patient’s vitals and physical exam normalized on hospital day one with continued supportive care and she was subsequently transferred to the inpatient psychiatry service.
Faculty Reviewer: Dr. Jason Hack
Boyer, E. and Michael Shannon. “The serotonin syndrome.” N Engl J Med 2005;352:1112-20.
Boyer, E. “Serotonin syndrome (serotonin toxicity).” UpToDate.
LoVecchio, F. and Erik Mattison. “Atypical and serotonergic antidepressants: Serotonin Syndrome.” Tintinalli’s Emergency Medicine: a comprehensive study guide 8e (2016).