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DQ-1

N-Acetylcysteine for reversal of Tylenol overdose

As acetaminophen has become commonly used in adults and children as an analgesic and antipyretic, it has also become a common cause of drug poisoning (Yesil & Ozdemir, 2018). This drug poisoning usually results in hepatic failure (Yesil & Ozdemir, 2018). Overdose of acetaminophen occurs due to CYP450 metabolizes acetaminophen into a toxic metabolite, N-Acetyl-p-benzoquinoneimine, and being unable to be conjugated with gluathione in an overdose setting due to the depletion of gluathione (Yesil & Ozdemir, 2018). With gluathione being depleted, the toxic metabolite builds and causes hepatocellular injury (Yesil & Ozdemir, 2018).

Acetylcysteine is the prefered antidote and is almost 100% effective if given within 8 hours post ingestion of acetaminophen (Ershad & Vearrier, 2019). Acetylcysteine is also approved for conditions with abnormal, viscid, or inspissated mucous secretions such as pneumonia, bronchitis, tracheobronchitis, cystic fibrosis, tracheotomy patients, post operative pulmonary complications, post traumatic chest conditions and before diagnostic bronchoscopy to help with mucosal plugging (Ershad & Vearrier, 2019).

The mechanism of action of acetylcysteine is that it provides a large substantial increase in glutathione reserves by providing the body with cysteine which is essential in glutathione production (Ershad & Vearrier, 2019). In addition, it also binds to toxic metabolites that are produced by the metabolism of acetaminophen (Ershad & Vearrier, 2019). Acetylcysteine also increase oxygen delivery to tissues, increases mitochondrial ATP production, and alters microvascular tone to increase blood flow and oxygen delivery to other vital organs (Ershad & Vearrier, 2019).

Administration of acetylcysteine depends on the overdose likelihood due to a necessity of the time and quantity of acetaminophen that was taken (Ershad & Vearrier, 2019). Also, a complete medication history is important due to that if the patient is taking any coingestants like anticholinergic or opioids that could cause a delayed absorption of acetaminophen is necessary (Ershad & Vearrier, 2019). There is a nomogram that is available that can help track acetaminophen levels and help providers determine if acetylcysteine is necessary (Ershad & Vearrier, 2019). If it is deemed necessary due to acetaminophen levels are greater than 10mg/L, then acetylcysteine should be given and can be given either orally or intravenously with minimal differences in efficacy (Ershad & Vearrier, 2019). There are two regimens followed which are a 21 hour IV protocol and a 72 hour oral protocol (Ershad & Vearrier, 2019). For the IV protocol the loading dose is 150mg/kg with a max of 15 gm, with a second dose of 50mg/kg up to a maximum of 5 gm, and a third dose of 100mg/kg up to a maximum of 10 gm (Ershad & Vearrier, 2019). The dosing schedule for the oral dose is 140 mg/kg loading dose orally, and after that 70mg/kg should be taken every 4 hours (Ershad & Vearrier, 2019).

Contraindications include patients with renal failure due to the amount of fluid mixed with the iv administration could cause fluid overload in some patients (Ershad & Vearrier, 2019). However, this can be managed easily with a pharmacist help to reduce the quantity of diluent fluid in the iv administration route (Ershad & Vearrier, 2019).

Monitoring includes hospital admission and for signs of manifestations of anaphylactoid reactions (Ershad & Vearrier, 2019). There is a rare chance for toxicity (Ershad & Vearrier, 2019).

Toxicity includes hemolysis, thrombocytopenia, metabolic acidosis, and acute reanal failure if acetylcysteine overdose occurs (Ershad & Vearrier, 2019). One example include a 23 year old female who recieved 100gm instead of 10gm of acetylcysteine, and eventually died after developing the previous complications and hemolytic uremic syndrome (Ershad & Vearrier, 2019).

References: Ershad M. & Vearrier, D. N., (2019). Acetylcysteine. StatPearls Publishing. from: https://www.ncbi.nlm.nih.gov/books/NBK537183/ Yesil, Y., & Ozdemir, A. A. (2018). Evaluation of the children with acute acetaminophen overdose and intravenous N-acetylcysteine treatment. Pakistan Journal of Medical Sciences, 34(3), 1–5. https://doi-org.lopes.idm.oclc.org/10.12669/pjms.343.14937

DQ-2

A protocol we follow in the MSICU is a CIWA protocol for acute alcohol withdrawal. Living in SW FL, we do see a lot of elderly people who come into the hospital, and within two to three days begin exhibiting signs of acute alcohol withdrawal. Most of the time the patients either fail to report or under-report the amount of alcohol they drink for a variety of reasons. At this point, it usually is only a matter of time until the truth comes out.

CIWA stands for the Clinical Institute Withdrawl Assessment-Alcohol, revised or CIWA-Ar (Eloma, Tucciarone, Hayes, & Bronson, 2018). This tool provides guidance for the measurement of severity and clinician guidance for benzodiazepine treatment (Eloma et al., 2018). The use of the CIWA-Ar protocol has been shown to drastically improve quality of care, patient safety, staff safety, and treatment effectiveness (Melkonian et al., 2019).

The first part of the CIWA scale is a measurement tool to help determine the level of acute withdrawal (Eloma et al., 2018). There are several questions with result criteria that give a point value and the total of these will indicate what level the patient fits into (Eloma et al., 2018). The questions include if the patient is experiencing : nausea and vomiting (0-7), tremors (0-7), anxiety (0-7), agitation (0-7), paroxysmal sweats (0-7), orientation (0-4), auditory disturbances (0-7), Tactile disturbances (0-7), tactile disturbances (0-7), visual disturbances (0-7), and headache (0-7) (Eloma et al., 2018). The level that the patient falls into also determines the frequency of reassessing the CIWA scale. For example, if they are level one, they would be assessed every 4 hours, level two would be every hour for eight hours and if stable then every other hour, and level three is to assess the score every hour (Eloma et al., 2018).

The CIWA orders measures the level of alcohol withdrawal against the patients ramsey sedation scale (Eloma et al., 2018). The inclusion of a banana bag which is made up of thiamine and folic acid, is up to the provider if they want to include a daily dose but it is highly recommended (Eloma et al., 2018). There are three levels that a patient can fit into (Eloma et al., 2018). The first level is a CIWA score of 1-7, level two is a CIWA of 8-15, and level three is a CIWA above 15 (Eloma et al., 2018). As the patient increases in level, so does the level of care, frequency of monitoring, and the level of medications available (Eloma et al., 2018). For example, level one includes ativan IV every two hours as needed for withdrawal symptoms for 48 hours with a PO version every two hours based on route available as well as vital signs every four hours (Eloma et al., 2018). Moving to level three includes vital signs every one hour, transfer to ICU, IV ativan every hour while awake, an additional dose every 4 hours, and a PRN ativan dose for agitation (Eloma et al., 2018). Included in level one is 10 mg of Librium TID and level three is 25 mg of Librium TID (Eloma et al., 2018). There are additional orders recommended such as clonidine 0.1 mg Po every 4 hours as needed for nausea and abdomnial cramps or diarrhea (Eloma et al., 2018). Also is the recommended Nicotine patch of 21mg every 24 hours if the patient smokes (Eloma et al., 2018).

With this scale and using it in the MSICU regularly, I have found it to be extremely helpful with some restrictions. Most of the time we receive elderly patients who under-report or neglect to report that they consume alcohol and how much. At this point it is usually a matter of time until we observe classic signs of acute withdrawal such as tremors, confusion, and agitation. Once we reach this we then ask the patient or family again and usually they are truthful at this time and we find out that they drink a fifth of vodka per day or a 12 pack of beer per day.

The restrictions I have noticed with the CIWA scale is the judgement of the nurse is entirely important at this time. Currently the CIWA scale gives the ability for a level three patient to receive 2mg of ativan every hour for 24 hours , with additional doses at the every four and eight hour marks. In my opinion this is an extreme amount of ativan to receive and I have advocated for the inclusion of romazicon in the order set at my local hospital. I do not believe every patient needs this much, but I realize some of them do. I do also realize that there are some extreme cases where this may be necessary to sedate a patient for their safety and the staffs safety, but also at those points I question whether or not we should intubate and sedate the patients that are that agitated. I have observed these patients become so agitated that they start experiencing hypertensive and cardiac events which could lead to larger problems if they are not properly managed.

Once we get them on the CIWA protocol, managment of the patient becomes a lot easier because we are usually able to sedate them to a point where they are awake, but are also following medical instruction and taking their prescribed medications. I have noticed that without CIWA the length of time of withdrawals is usually 5-7 days in an elderly population, but with the addition of the CIWA protocol it shortens it to 3-5 days. This could be that they are taking all of their medications appropriately, and adhering to medical advice leading to a quicker recovery time. Or that the administration of benzodiazepimes and libruim end up treating withdrawal symptoms themselves and masking the actual duration of the withdrawal state.

References: Eloma, A. S., Tucciarone, J. M., Hayes, E. M., & Bronson, B. D. (2018). Evaluation of the appropriate use of a CIWA-Ar alcohol withdrawal protocol in the general hospital setting. American Journal of Drug & Alcohol Abuse, 44(4), 418–425. Melkonian, M., Patel, M., Magh, M., Ferm, M., & Hwang, M. M. (2019). Assessment of a Hospital-Wide CIWA-Ar Protocol for Management of Alcohol Withdrawal Syndrome. Mayo Clinic Proceedings: Innovations, Quality & Outcomes, 3(3), 344–349. https://doi-org.lopes.idm.oclc.org/10.1016/j.mayocpiqo.2019.06.005

DQ-3

Amiodarone is a lipophilic antiarrhythmic medication used in the treatment of ventricular tachycardia, ventricular fibrillation, atrial fibrillation, and paroxysmal supraventricular tachycardia. Amiodarone blocks voltage gated potassium and calcium channels. Toxicities include pulmonary toxicity and hepatotoxicity and increased cardiac arrhythmias (Amiodarone (Professional), 2020). IV lipid emulsion therapy has become a life saving procedure for many patients experiencing overdoses or toxic levels of calcium channel blockers. Though the mechanisms of action are poorly understood, researchers have developed a “lipid sink” theory. It is believed that the fat emulsion surrounds the lipophilic drug and renders it ineffective as it drowns the drug in a compartment known as the lipid sink. Another theory involves the fat emulsion acting as a fuel source for the impaired cardiovascular system (Karcioglu, 2017). Side effects include headache, nausea, vomiting, dizziness and flushing. Serious side effects are shortness of breath, pain at insertion site, sudden weight gain, and chest pain, however, these side effects are rarely seen in patients (Intralipid 20, 2020). IV lipid emulsions have proven to be a rescue medication in many cases of calcium channel blockers and it has been used extensively in emergency situations when the patient experiences refractory cardiac events from anesthetics (Karcioglu, 2017).

Reference

Amiodarone (Professional) (2020). Drugs.Com. Retrieved from https://www.drugs.com/amiodarone.html.

Intralipid 20 (2020). RXlist Professional. Retrieved from https://www.rxlist.com/intralipid-20-side-effects-drug-center.htm#overview

Karcioglu O. (2017). Use of lipid emulsion therapy in local anesthetic overdose. Saudi medical journal, 38(10), 985–993. https://doi.org/10.15537/smj.2017.10.20525