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Phenobarbital as First-Line Medication for Alcohol Withdrawal: Have You Switched From Benzodiazepines Yet?

phenobarbital first line monotherapy for alcohol withdrawal

Are you using phenobarbital instead of benzodiazepines as the first-line monotherapy for patients in alcohol withdrawal in the Emergency Department (ED)? If not, you probably should be. Another old drug for a new indication, right? Well not exactly. Phenobarbital is indeed an older and relatively cheap drug (less than $20 per loading dose) that has gained some press recently for the treatment of acute alcohol withdrawal [1-3].

Why should you consider using phenobarbital as monotherapy rather than benzodiazepines?

Phenobarbital used to be one of the standard treatments for ethanol (EtOH) withdrawal prior to the introduction of benzodiazepines. However, there are key advantages over benzodiazepines.

  1. Phenobarbital has a dual mechanism of action, binding both the GABA receptor and glutamate receptors in the CNS [3]. This helps EtOH withdrawal symptoms by up-regulating GABA activity and down-regulating excitatory glutamate activity.
  2. Phenobarbital has a predictable metabolization with a long half-life of approximately 3-5 days, which allows the drug to self-taper after the initial loading dose and symptom control in the ED [1, 2]. This contrasts the relatively shorter half-life of many available benzodiazepines, which often require more frequent redosing.

Is phenobarbital safe for the treatment of EtOH withdrawal in the ED?

In short, yes. Several studies have indicated that dosing with phenobarbital (PO or IV) is safe and effective at decreasing the need for escalating doses of benzodiazepines for EtOH withdrawal [1-6]. In comparison to benzodiazepines, it demonstrated:

  • Fewer episodes of hypotension and apnea [1-6]
  • Decreased hospital and ICU stay duration in admitted patients [1]
  • Decreased requirement for ICU level care [1]

Dosing regimens

  • Common regimen: 10-15 mg/kg of IDEAL body weight (IBW) IV bolus over 30 minutes and administering 130-260 mg aliquots every 15-30 minutes for persistent symptoms [2]
    • Note that the patient’s IBW may be much lower than the actual body weight.
    • Use the MD Calc calculator for a patient’s IBW
    • Examples based on the average American height:
      • Male: 5’9” –> 71 kg IBW –> phenobarbital 710-1065 mg IV initial bolus
      • Female: 5’4” –> 55 kg IBW –> phenobarbital 550-825 mg IV initial bolus
  • Alternative lower dosing regimen: 130-260 mg IV boluses with repeated dosing as needed [3]
  • Maximum dose
    • No established maximum, but the absolute upper limit for dosing in epilepsy is 20-30 mg/kg [11]
    • Some sources recommend limiting the dose of phenobarbital in alcohol withdrawal to 15 mg/kg/day [3]
  • Adjuncts: Benzodiazepines may be added without decreasing safely [1]

Do patients need phenobarbital dosing adjustments if they have liver dysfunction?

  • Phenobarbital undergoes metabolization primarily in the liver, mostly by CYP2C9 [9].
  • “Dose adjustment” is recommended by the manufacturer in hepatic dysfunction, but no value is provided [10].
    • Since there is no recommended dosing adjustment in patients with cirrhosis and liver dysfunction, a conservative approach starting with the 130 mg boluses and titrating to the minimum effective dose would likely be the safest approach.
  • Clinical pearl: Hepatic encephalopathy is a strong contraindication to phenobarbital [9, 10].
    • Before administering a barbiturate to a cirrhotic patient for EtOH withdrawal, first ensure that hepatic encephalopathy is not the cause of the agitation or altered mental status.
    • Because patients with hepatic encephalopathy experience excess GABA stimulation, they are very sensitive to GABAergic medications (e.g., barbiturates or benzodiazepines).
    • Administration of benzodiazepines or barbiturates to these patients risk inducing a prolonged comatose state.

Is it safe to give phenobarbital to a patient who has already received benzodiazepines?

  • The concern with concurrent phenobarbital and benzodiazepine administration is oversedation. There is a paucity of evidence for this question, although preliminary data suggests that it is safe without significant mortality risk [1].
  • As a corollary, exercise caution when administering phenobarbital to patients at risk for sedation from any cause, such as hepatic encephalopathy, benzodiazepine abuse, and opioid abuse.
  • Suggested approach: If benzodiazepines have already been given, consider using the alternative, more conservative, lower dose regimen protocol (130-260 mg doses) up to 10-15 mg/kg total with close monitoring after every up-titration. Avoid giving benzodiazepines concurrently during the phenobarbital up-titration period to minimize the risk of oversedation and apnea [11].

Which patients treated with phenobarbital require admission?

There is a dearth of evidence about which patients require medical admission in the setting of phenobarbital administration. The American Society of Addiction Medicine has developed a tool to assist providers with disposition planning for patients with alcohol withdrawal syndrome for all-comers (not necessarily those treated with phenobarbital) [2]. Their recommendations are as follows:

  • Outpatient management
    • Able to follow return precautions
    • Likely to continue with alcohol use disorder treatment
    • Supportive living environment
  • Inpatient management
    • Requires frequent physician and nursing intervention
    • Heavy sedation requirements or active delirium tremens
    • Coexisting medical diagnoses that require inpatient management (severe electrolyte anomalies, infections, pancreatitis, hepatic encephalopathy, etc.)
    • History of severe withdrawals, pregnancy, or concurrent medical condition requiring treatment

Conclusion

Phenobarbital has gained significant popularity for use in EtOH withdrawal in the last few years. Several factors make it ideal for use in EtOH withdrawal, primarily its long half-life allowing for a multi-day, self-tapering effect. The most commonly recommended dosing regimen starts with a 10 mg/IBW kg bolus followed by titration every 30 minutes afterwards. Patients in the ED often can be safely phenobarbital-loaded and discharged, assuming hemodynamic stability, normal alertness, and resolution of withdrawal symptoms. More rigorous studies are needed determine dose thresholds that warrant hospital admission.

References

  1. Rosenson J, Clements C, Simon B, et al. Phenobarbital for Acute Alcohol Withdrawal: A Prospective Randomized Double-blind Placebo-controlled Study. The Journal of Emergency Medicine. 2013;44(3):592-598.e2. doi:10.1016/j.jemermed.2012.07.056. PMID: 22999778
  2. Wolf C, Curry A, Nacht J, Simpson SA. Management of Alcohol Withdrawal in the Emergency Department: Current Perspectives. Open Access Emerg Med. 2020;12:53-65. doi:10.2147/OAEM.S235288. PMID: 32256131
  3. Long D, Long B, Koyfman A. The Emergency Medicine Management of Severe Alcohol Withdrawal. The American Journal of Emergency Medicine. 2017;35(7):1005-1011. doi:10.1016/j.ajem.2017.02.002. PMID: 28188055
  4. Staidle A, Geier C. Phenobarbital and/or Benzodiazepines for Recurrent Alcohol Withdrawal: A Self-Controlled, Retrospective Cohort Study. The American Journal of Emergency Medicine. 2022;54:263-266. doi:10.1016/j.ajem.2022.02.020. PMID: 35219012
  5. Lebin JA, Mudan A, Murphy CE, Wang RC, Smollin CG. Return Encounters in Emergency Department Patients Treated with Phenobarbital Versus Benzodiazepines for Alcohol Withdrawal. J Med Toxicol. 2022;18(1):4-10. doi:10.1007/s13181-021-00863-2. PMID: 34697777
  6. Hendey GW, Dery R, Barnes R, Snowden B, Mentler P. A Prospective, Randomized, Trial of Phenobarbital Versus Benzodiazepines for Acute Alcohol Withdrawal. The American Journal of Emergency Medicine. 2011;29(4):382-385. doi:10.1016/j.ajem.2009.10.010. PMID: 20825805
  7. Hoffman PL, Grant KA, Snell LD, Reinlib L, Iorio K, Tabakoff B. NMDA Receptors: Role in Ethanol Withdrawal Seizures. Annals of the New York Academy of Sciences. 1992;654(1):52-60. doi:10.1111/j.1749-6632.1992.tb25955.x. PMID: 1321581
  8. Young GP, Rores C, Murphy C, Dailey RH. Intravenous Phenobarbital for Alcohol Withdrawal and Convulsions. Annals of Emergency Medicine. 1987;16(8):847-850. doi:10.1016/S0196-0644(87)80520-6. PMID: 3619162
  9. Patsalos PN, Spencer EP, Berry DJ. Therapeutic Drug Monitoring of Antiepileptic Drugs in Epilepsy: A 2018 Update. Therapeutic Drug Monitoring. 2018;40(5):526-548. doi:10.1097/FTD.0000000000000546. PMID: 29957667
  10. Lewis CB, Adams N. Phenobarbital. In: StatPearls. StatPearls Publishing; 2023. Accessed April 16, 2023.
  11. Farkas J. Alcohol withdrawal. EMCrit Project. Published March 29, 2023. Accessed April 18, 2023.
By |2023-05-31T19:25:45-07:00Jun 1, 2023|Neurology, Tox & Medications|
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Trick of Trade: Dual Foley catheter to control massive epistaxis

Massive epistaxis is considered a medical emergency that requires immediate attention. Symptoms of massive epistaxis include sudden and heavy bleeding from the nose, difficulty breathing, dizziness, and a rapid heartbeat. If left untreated, it can lead to significant blood loss, shock, airway obstruction, and even death. We report a case of a 50-year-old man with end stage renal disease with massive nasal bleeding from the left nostril, shortness of breath, and confusion.

Initial Management

After a rapid assessment, we inserted an anterior nasal pack, soaked in epinephrine, TXA, and an antibiotic-based lubricant. However, the bleeding continued from his nares and posterior oropharynx. We thus removed the anterior packing and instead inserted a Foley catheter into the posterior nasal space and inflated the balloon. Unfortunately, the bleeding still continued. Because he presumably had uremia-induced thrombasthenia (weak platelets), he received blood transfusions and IV TXA. And still — he continued bleeding heavily.

Trick of the Trade: Dual Catheter Technique

To provide optimal surface area coverage and tamponade effect of the posterior vessels, concurrent anterior packing is usually needed [1]. You can use commercial devices that have a dual balloon setup, but we did not have that available.

dual balloon for massive epistaxis

Illustration by Dr. Abdelhameed with patient-consented photo of dual balloon technique

Technique

  1. Insert the a 14-French Foley catheter into the nares with the patient’s mouth open (balloon 1). Stop when you see the tip of the catheter dangling in the posterior oropharynx.
  2. Inflate the balloon partially with 15-20 cc of air.
  3. Gently pull the catheter anteriorly until you feel resistance such that the balloon is snuggly positioned.
  4. If the bleeding still continues, insert a second Foley catheter until you meet resistance (balloon 2). Inflate this second balloon with 15 cc of air.

For our case, this dual catheter compression technique succeeded in halting the bleed.

Interested in Other Tricks of the Trade?

Reference

  1. Goralnick E. Posterior Epistaxis Nasal Packing. Medscape. Published Dec 9, 2020
By |2023-05-23T23:11:19-07:00May 29, 2023|Genitourinary, Pediatrics, Tricks of the Trade|
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Trick of Trade: Removal of Entrapped Metal Zipper

zipper entrapment injury

A young boy is brought to the pediatric emergency screaming at the top of his lungs by his parents. His penile skin is trapped in the zipper of his jeans. On a busy shift, you want a simple way to handle zipper injuries that minimizes pain, doesn’t require resource-intensive procedural sedation, and is quick.

Background

The 4 most common types of zippers are nylon coil zip, plastic mold zip, metal zip, and invisible zip. Most of the techniques describing solutions on zipper entrapment in the medical literature are derived from case reports and case series. All revolve around understanding zipper anatomy and obtaining adequate exposure to assess how the skin is entrapped. The penile skin often is entrapped either in the sliding mechanism (also known as the endplate) or between the teeth of the zipper.

zipper anatomy

Figure 1. Anatomy of a zipper

Penile Entrapment Injury Management Techniques in Literature

Reported techniques for releasing zippers include [1, 2]:

  • Cut the sliding mechanism (aka the endplate) using metal cutters.
  • Use a flat screwdriver placed underneath the sliding mechanism and rotate it.
  • Use mineral oil for lubrication.
  • Use lateral compression technique to relieve the tension on the trapped skin.
  • Cut the zipper and pull the teeth apart.

All these techniques are associated with variable rates of success. Some of these techniques such as using metal cutters might lead to iatrogenic injuries.

The problem is that the child’s penile skin is entrapped within a metal zipper, where many recommended methods for zipper entrapment removal won’t work.

Trick of the Trade: Removing Metal Zippers

Materials Needed

  • Lidocaine gel
  • Blade or scissors

Technique

  1. The zipper should be separated from the pants as much as possible to minimize painful stretching or pulling of the penile skin.
  2. Apply lidocaine gel on the area of entrapment for 2-3 minutes.
  3. Identify the exposed teeth closest to slider and cut off the zipper at that level (blue dots) while avoiding penile skin (Figure 2).
  4. Gently advance the zipper body forward, pulling either the tab or the body itself, to disengage it from the teeth. You may need to add more lidocaine gel or other lubrication to facilitate this sliding motion.
  5. The remaining parts of the zipper can easily be disengaged from the skin (Figure 3).

metal zipper cut trick zipper entrapment

Figure 2. Cutting off the zipper between the teeth (blue dots) and advancing the zipper body (yellow arrow)

metal zipper entrapped free

Figure 3. Freed zipper body

Interested in Other Tricks of the Trade?

References

  1. Leslie SW, Sajjad H, Taylor RS. Penile Zipper and Ring Injuries. [Updated 2023 Mar 11]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
  2. Tasian GE, Belfer RA. Genitourinary trauma. In: Fleisher and Ludwig’s Textbook of Pediatric Emergency Medicine, 7th ed, Shaw K, Bachur RG (Eds), Lippincott Williams & Wilkins, Philadelphia 2015.
By |2023-05-23T21:20:02-07:00May 24, 2023|Genitourinary, Pediatrics, Tricks of the Trade|
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Trick of Trade: Inflating the Esophageal Balloon of a Blakemore/Minnesota Tube without a Manometer 

esophageal balloon manometer trick minnesota blackmore tube

A heavy alcohol drinker, who is well known to your Emergency Department, presents with altered mental status, except that he looks different this time. He looks really bad, stating that he has been vomiting blood. He is hypotensive. He then vomits a copious amount of blood right in front of you. You intubate the patient and initiate the massive transfusion protocol, but everything you pour into him seemingly comes right back out. The gastroenterologist on-call states that he is too unstable for endoscopy. It is time for a balloon tamponade device. You’ve trained for this and set up everything. You call the respiratory therapists (RT) for this mystical “manometer” that you have seen in instructional videos, except that they look puzzled by your request. It is time to MacGyver a method that allows you to know the esophageal balloon pressure that you are generating to avoid an esophageal rupture.

esophageal balloon devices linton sengstaken blakemore minnesota tube

Esophageal Balloon Tamponade Devices – Linton-Nachlas, Sengstaken-Blakemore, Minnesota Tubes (image courtesy of Dr. Mark Ramzy at REBEL EM)

What are esophageal balloon tamponade devices?

There are 2 commonly used devices for tamponading the esophagus during a variceal bleed, the Sengstaken-Blakemore (SB) tube and the Minnesota tube. There is also the Linton-Nachlas tube, but that only has a gastric balloon. The SB tube was created in 1950 in order to help tamponade variceal bleeds [1]. It is a 3-lumen device that has ports to inflate the gastric balloon, aspirate gastric contents, and inflate an esophageal balloon. The Minnesota tube was developed later as a variation to the SB tube and contains an additional port and lumen for aspirating esophageal contents [2]. Another minor difference is that the gastric balloon in the Minnesota tube holds 450-500 ccs of air, while the SB gastric balloon holds 250 ccs of air [2].

Indication: The uncontrolled hemorrhage from esophageal or gastric variceal bleeding after medical or endoscopic treatment fails, is not available, or is not technically possible [3, 4].

Contraindications [4]:

  • Unprotected airway
  • Esophageal rupture (Boerhaave’s syndrome)
  • Esophageal stricture
  • Uncertainty of bleeding site
  • Well-controlled variceal bleeding

Esophageal balloon tamponade devices achieve hemostasis in 60-90% of cases; however, they are only a temporary measure of hemorrhage control because over 50% of variceal bleeds rebleed after deflation [5].

How do you insert these esophageal tamponade devices?

The following instructions are for inserting a Sengstaken-Blakemore (SB) tube [3, 6]:

  1. Pre-measure 50 cm above the gastric balloon and esophageal balloon and mark them on the SB tube.
  2. Fully lubricate the tube.
  3. Insert the tube similar to an orogastric tube until you have reached the 50 cm mark for the gastric balloon
    • Additional trick: You can insert it with a nasogastric tube to have more rigidity and make inserting the tube easier.
  4. Use a slip syringe at the gastric aspiration site and auscultate to confirm that you are in the stomach. Then fill the gastric balloon with 50 cc of air.
  5. Verify the placement of the gastric balloon with a chest x-ray.
    • Additional trick: If the x-ray is delayed, you can pre-check with ultrasound [7]. However final confirmation prior to full inflation should be with a chest X-ray.
  6. Fully inflate the gastric balloon with 200 more ccs of air for a total of 250 ccs.
    • The Minnesota tubes should have the gastric balloon inflated to 450-500 ccs.
  7. Apply traction to the tube by tying a roller bandage to the end of it and then the other end to a 1 L bag of IV fluids. Then hang the roller bandage over an IV pole.
  8. Place the nasogastric tube down to the pre-measured level above the gastric balloon and suction the esophageal space. If there is continued bleeding coming from the nasogastric tube then you will need to inflate the esophageal balloon.
    • Note that Minnesota tubes already have their own esophageal suction port and will NOT need this NG tube placement to suction the esophagus.
  9. Use a “manometer” to inflate the esophageal balloon to 30 mmHg. If bleeding persists, you can go to a maximum of 45 mmHg.

What is this “manometer” typically used for the esophageal balloon?

The manometer referenced in numerous videos [6, 8] is actually a cuff manometer, or pressure gauge, to measure endotracheal cuff pressures. Hence, the RT’s are supposed to have them. In our emergency department, the RTs do not spend a lot of time going around measuring cuff pressures and usually save that until the patient reaches the ICU. It is convenient to use for the inflation of the esophageal balloon because it can inflate and measure pressure at the same time.

Pearl 1: Check the units of pressure being used. Manometers often use cmH2O, while esophageal balloons use mmHg.

  • The conversion rate is: 1 cmH2O = 0.74 mmHg
  • The esophageal balloon goal of 30-45 mmHg is approximately 40-60 cm H2O.

Pearl 2: While the gastric balloon sets a target VOLUME, the esophageal balloon sets a target PRESSURE.

Trick of the Trade: Use a sphygmomanometer as the manometer

Once the inflated gastric balloon is confirmed to be in place, it is time to inflate the esophageal balloon. A manual blood pressure instrument can be repurposed to inflate and measure the esophageal balloon pressure.

  1. Take your manual blood pressure cuff and detach the connections so you have only a plastic tube that runs to the pressure gauge.
  2. Connect this plastic tube end to the male Luer lock of a 3-way stopcock.
  3. Connect the esophageal balloon to a female luer lock on the 3-way stopcock.
  4. Place a 50 cc syringe on the final female Luer lock of the 3-way stopcock.
  5. Turn the 3-way stopcock off towards the pressure gauge and inflate the esophageal balloon with 10 ccs of air.
  6. Then turn the 3-way stopcock off towards the syringe and you should have a reading on the pressure gauge.
  7. Repeat this using small increments (we chose 10 ccs) until you have a pressure reading of 30 mmHg on the pressure gauge. If bleeding continues, you can increase to 45 mmHg.

Video Demonstration: Esophageal Balloon Inflation

References

  1. Sengstaken RW, Blakemore AH. Balloon tamponage for the control of hemorrhage from esophageal varices. Ann Surg. 1950 May;131(5):781-9. doi: 10.1097/00000658-195005000-00017. PMID: 15411151; PMCID: PMC1616705.
  2. Nickson C. Sengstaken–Blakemore and Minnesota Tubes. Life in the Fast Lane • LITFL. Published January 30, 2019.
  3. Powell M, Journey JD. Sengstaken-Blakemore Tube. [Updated 2022 Jun 5]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-.
  4. Yartsev A. Sengstaken-Blakemore, Minnesotta and Linton-Nachlas tubes. Deranged Physiology. Published July 13, 2015. Accessed April 6, 2023.
  5. García-Pagán JC, Reverter E, Abraldes JG, Bosch J. Acute variceal bleeding. Semin Respir Crit Care Med. 2012 Feb;33(1):46-54.
  6. Mason J. Placement of a Blakemore Tube for Bleeding Varices. EM:RAP HD Videos. Accessed December 17, 2021.
  7. Farkas J. PulmCrit Wee: Ultrasound-guided blakemore tube placement. EMCrit Project. Published May 4, 2016. Accessed April 6, 2023.
  8. Roohollahi A, Suleiman Bilal Rana H, Hadique S. Blakemore Tube Insertion – BAVLS. American Thoracic Society. Published June 1, 2020. Accessed April 7, 2023.
By |2023-05-23T12:22:38-07:00May 19, 2023|Critical Care/ Resus, Gastrointestinal, Tricks of the Trade|
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