IV Medications and Torsades de Pointes: An Evidence Based Review

1. IV Medications andTorsades de Pointes:An Evidence Based Review NUR-271 2011 By Amanda Feczko, Jennifer Nielson, Jessica Esquivel Cami Dunn, Ron Klug

2. The American Association of Critical-Care Nurses (AACN) has endorsed recommendations to prevent a medication-induced heart rhythm problem in hospital settings. The association is concerned about preventing the occurrence of Torsade de Pointes (TdP), a rare heart rhythm associated with a drop in blood pressure. It can cause fainting or lead to ventricular fibrillation and sudden cardiac arrest. • A statement released by the American Heart Association and the American College of Cardiology. It describes the ways in which certain medications — including intravenous antibiotics, antipsychotics, and anti-arryhmia drugs — can prolong the heart’s Q-T interval.

3. Situation: • In the acute health care settings there are many medications that exacerbate pre-existing cardiac conditions causing sudden cardiac death (Woosley & Romero, 2009). • Would it be prudent and effective care to provide cardiac monitoring for patients with pre-existing cardiac conditions who are receiving intravenous (IV) antibiotics or antipsychotic medications while hospitalized? RK

4. Situation Evidence Several studies have since taken place that examine the link between certain medications and fatal arrhythmias • UK database illustrates reports of 31 unexplained deaths and 63 fatal cardiac arrhythmias associated with 11 antipsychotic agents. • 1988-1993, examination of 500,000 Tennessee residents on Medicaid on prescribed antipsychotics revealed that they had 2.39 times more incidences of sudden cardiac death with 1,487 confirmed cases. • Three observational study designs using different control options showed a link in ventricular arrhythmias/cardiac arrest with recent use of specific antibiotics (Zambon, Polo Friz, Contiero, & Corrao, 2009). AF

5. PICO Statement • P- Sudden cardiac death secondary to administration of IV antibiotic/antipsychotic medications to patients with cardiac risk factors(AHA, 2010). • I- Administration of IV antibiotics/antipsychotics. • C- Cardiac monitoring of patients receiving IV antibiotics/antipsychotics. • O- Decreased morbidity and mortality of patients receiving IV antibiotics/antipsychotics (Slama, 2005). RK

6. Background • Initially in both 1987 and 1997, the American Psychiatric Association and the Royal College of Psychiatrists determined there was insufficient epidemiological evidence to support the causal relationship between certain medications and fatal cardiac disturbances. On the other hand, they did concede the existence of a possible link (Zambon, Polo Friz, Contiero, & Corrao, 2009). • Though the risk of TdP or sudden death was unclear, there has been enough concern to remove many of the QT prolongation medications from the market, or replace them with restrictive labeling (Haddad & Anderson, 2002). AF

7. Background (cont) • QT Interval = onset of electrical depolarization of the ventricles and the end of depolarization. • Prolongation of this interval can be the marker of several medications (Klabunde, 2007). • Table I. Drugs associated with QT prolongation[7,8]a • Antiarrhythmic drugs Class 1a • Disopyramide • Procainamide • Quinidine • Class 3 • Amiodarone • Bretylium • Dofetilide • Sotalol • Antihistamines Astemizole (withdrawn in the UK) • Terfenadine (withdrawn in the USA) • Antimicrobial agents Fluoroquinolone antibiotics • Grepafloxacin • Levofloxacin • Sparfloxacin • Macrolide antibiotics • Clarithromycin • Erythromycin • Imidazolineantifungals • Ketoconazole • Antimalarials • Chloroquine • Halofantrine • Quinine • Miscellaneous antimicrobials • Cotrimoxazole • Pentamidine • Spiramycin • Calcium antagonists Prenylamine (withdrawn in the UK) • Terodiline (withdrawn in the UK) • Miscellaneous • nonpsychotropic drugs • Cisapride (withdrawn in the UK) • Probucol • Tricyclic and related • antidepressant drugs • Amitriptyline • Clomipramine • Desipramine • Doxepin • Imipramine • Maprotiline • Nortriptyline • Typical antipsychotic • drugs • Chlorpromazine • Droperidol (withdrawn in the UK) • Fluphenazine • Haloperidol • Mesoridazine • Pimozide • Sulpiride • Thioridazine • Trifluoperazine • Atypical antipsychotic • drugs • Sertindole (voluntarily suspended in Europe) • Ziprasidone • Miscellaneous • psychotropic drugs • Chloral hydrate • Lithium • a This list is not comprehensive and is given to indicate the diversity • of drugs involved. The drugs listed differ with regard to • their effect on QT prolongation. Some have marked effects • while others have minor effects. AF

8. Background (cont) • Torsades de Pointes(TdP), is a polymorphic ventricular arrhythmia that can progress to v-fib of sudden death • Characterized by QRS complexes of changing amplitude that appear to “twist” around the isoelectric line • Can be asymptomatic, or can cause palpitations, dizziness or syncope in others (Roden, 1993). AF

9. Assessment • Relevance of QT prolongation depends on frequency and magnitude, and therefore is unpredictable from patient to patient • Some individuals may have predisposing factors of TdP that can become seriously compounded when given medications that prolong the QT interval: (Zimetbaum & Josephson, 1999) AF

10. Assessment (cont) • Table V. Risk factors for arrhythmias • Nonpharmacological risk factors • Congenital long QT syndromes • Individual predisposition • Specific cardiac disorders (e.g. ventricular hypertrophy, heart • failure, bradycardia) • Electrolyte imbalance (especially hypokalaemia) • Overdose of antipsychotic drug • Female sex • Restraint and psychological stress • Substance misuse • Miscellaneous factors • elderly • renal and hepatic impairmenta • slow metaboliserstatusa • Pharmacological risk factors • Pharmacokinetic factors • inhibition of specific cytochrome P450 enzymes • competition for specific cytochrome P450 enzymes • Pharmacodynamic factors • independent QTc prolongation • electrolyte disturbance • a Depending on metabolism and route of elimination of drug. AF

11. Recommendation for Monitoring • In an ideal situation all patients with cardiac risk factors on IV antibiotics, ie: Erythromycin, antipsychotics, ie: Thorazine and IV anti-arrythmicsie: Amiodarone should be placed on ECG monitoring on a telemetry unit (Drew, Califf, Funk, Kaufman, Krucoff, Laks, & Van Hare, 2005). • ECG monitoring can improve response times for TdP and decrease morbidity and mortality of patients (Slama, 2005). • Providing staff who are adequately trained to interpret and quickly manage any complications will improve outcomes for these patients. JS

12. Recommendation for Monitoring • Emergency/ICU cost- Avoiding an arrest is more cost effective than a transfer to the Intensive Care Unit (ICU) after a fatal arrhythmia caused by TdP. • Telemetry unit opportunities- Expansion/training opportunities, and potential higher acuity certifications could improve patient outcomes. • At discharge- Patients will receive focused teaching about side effects and possible complications related to the medications they are receiving. Further information can be given regarding Holter monitoring or various implanted devices (ICD’s) JS

13. Recommendation Against Monitoring • Lack of trained / experienced staff to interpret ECG’s • Availability of beds on Telemetry unit • Telemetry beds are a limited resource and many patients do not require telemetry monitoring just because they are hospitalized (Chen & Hollander, 2007) JN

14. Recommendation Against Monitoring • North Shore University Hospital • -Major cardiac referral center in NY metropolitan area • Conducted over 3 months • 414 patients presented to the ER with chest pain and/or associated symptoms that were admitted to the telemetry unit. • 63 patients had palpitations • 0 patients presented had ventricular arrhythmias • 210 of those 414 patients had normal ECG findings • The most common intervention to those admitted was a simple change in medication • -outpatient •   Of those presented to the Hospital with chest pain and/or associated symptoms such as palpitations, a majority had normal ECG. They are at a low risk for the life threatening arrhythmias and can best be managed as outpatients with better medication education. Not plugging up the telemetry unit using up valuable recourse and creating unnecessary costs (Snider, Papaleo, Beldner, Park, Katechis, Galinkin, & Fein, 2002). JN

15. Recommendation Against Monitoring • How Necessary is Monitoring? • Patient priority for telemetry is unclear and is it required? What if another patient requires telemetry and none is available? • With growing demands for telemetry, can the tele units provide safe, quality care and monitor patients appropriately? • Telemetry monitoring seldom leads to management changes by cardiologist (Chen & Hollander, 2007) JN

16. Recommendation Against Monitoring • Cost • Some perceive telemetry as higher level of care, but with higher level of care comes higher and potentially unnecessary cost. • Medicare has strict criteria for reimbursement for telemetry and will not pay if they deem it not necessary (CMS, 2006). • How to cut down on costs? • In the end operation cost will prevail over modernization projects (Dagrosa, 2003). JN

17. Implementation Develop protocol for standard practice for specific antibiotic, anti-arrhythmic, and antipsychotic medications that are linked to TdP. CD

18. Implementation • : Explore possibility/feasibility for use of internal ECG monitor. • - Continuous high risk meds • -Cost • -Health Risk • -PT education CD

19. Implementation • Improve education for prescribing physicians related to risk. • Ex. Prescribing alternative meds or Recommended necessary ECG monitoring. • Plan for continuing physician education: • -Medical Conventions: Guest speaker • -Internet courses for CEU's • -Drug reps/Drug companies CD

20. Implications for Nursing • If increased monitoring is indicated- • Possibly improve response time if TdP occurs (Slama, 2005). • The potential for overcrowding of telemetry units (Chen & Hollander, 2007). • The limited availability of staff for monitored beds. • Increased cost of healthcare due to increased monitoring/training of staff. • Possible lack of reimbursement for monitoring if deemed not medically necessary by Medicare (CMS, 2006). RK

21. Implications for Nursing (cont) • If increased monitoring is not indicated- • Potential for lack of observation of patients, leading to increased morbidity and mortality if TdP occurs. • Increased cost due to ICU stay following a cardiac event(Dagrosa, 2003). • Make telemetry available for patients who truly need it such as true cardiac patients such as CHF and AMI patients. RK

22. Resources Antimicrobial drug induced QTc interval prolongation: Assesment of QTc prolongation by antimicrobial class. (n.d.). Medscape: Medscape Access. Retrieved April 4, 2011, from http://www.medscape.com/viewarticle/409682_4 Chen, E. H., & Hollander, J. E. (2007). When do patients need admission to a telemetry bed?. Journal of Emergency Medicine, 33(1), 53-60. Retrieved April 3, 2011, from http://ttuem.com/page2/page5/files/Who%20Needs%20Tele.pdf Continuous ECG monitoring to prevent heart rhythm problem in critical care. (n.d.). AED - Automated External Defibrillator - EKG Machine ECG - Stress Test - Cardiac Science. Retrieved April 6, 2011, from http://www.cardiacscience.com/blog/2010/06/ecg-monitoring-to-prevent-critical-care-heart-problem/ Dagrosa, D. (2003). Championing change: Lessons learned from one unit's struggle. Nursing Economics, Nov-Dec(21), 302-305. Retrieved April 4, 2011, from http://findarticles.com/p/articles/mi_m0FSW/is_6_21/ai_n18616734/?tag=content;col1 Drew, B. J., Ackerman, M. J., Funk, M., Gibler, W. B., Kligfield, P., Menon, V., et al. (2010). Prevention of torsades de pointes in hospital settings. Circulation, 121(Febuary 2010), 1047-1060. Retrieved April 4, 2011, from http://circ.ahajournals.org/cgi/content/full/121/8/1047 Drew, B., Califf, R., Funk, M., Kaufman, E., Krucoff, M., Laks, M., & ... Van Hare, G. (2005). AHA scientific statement: practice standards for electrocardiographic monitoring in hospital settings: an American Heart Association Scientific Statement from the Councils on Cardiovascular Nursing, Clinical Cardiology, and Cardiovascular Disease in the Young: endorsed by the International Society of Computerized Electrocardiology and the American Association of Critical-Care Nurses... reproduced with permission. Journal of Cardiovascular Nursing, 20(2), 76-106. Retrieved from EBSCOhost JN

23. Resources Haddad, P., & Anderson, I. (2002). Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs, 62(11), 1649-1671. Retrieved from EBSCOhost. Klabunde, R. (2007, April 6). CV Physiology: Electrocardiogram (EKG, ECG). CV Physiology: Home Page. Retrieved April 4, 2011, from http://www.cvphysiology.com/Arrhythmias/A009.htm National coverage determinations with data collection as a condition of coverage: coverage with evidence development. (2006, July 12). Centers for Medicare and Medicaid Services (CMS). Retrieved April 3, 2011, http://www.cms.gov/medicare-coverage-database/details/medicare-coverage-document-details.aspx?MCDId=8&McdName=National+Coverage+Determinations+with+Data+Collection+as+a+Condition+of+Coverage%3A+Coverage+with+Evidence+Development&mcdtypename=Guidance+Documents&MCDIndexType=1&bc=BAAIAAAAAAAA& Roden, D. M. (1993). Torsades de pointes. Clinical Cardiology, 16(9), 683-686. Retrieved April 4, 2011, from http://www.ncbi.nlm.nih.gov/pubmed/7902224 Slama, T. G. (2005). Minimizing the risk for QT interval prolongation. Journal of Family Practice, June 2005. Retrieved April 3, 2011, from http://findarticles.com/p/articles/mi_m0689/is_6_54/ai_n27856562/pg_2/?tag=content;col1

24. Resources Snider, A., Papaleo, M., Beldner, S., Park, C., Katechis, D., Galinkin, D., & Fein, A. (2002). Is telemetry monitoring necessary in low-risk suspected acute chest pain syndromes?. CHEST, 122(2), 517-523. Retrieved from EBSCOhost. Woosley, R. L., & Romero, K. (n.d.). Medscape: Medscape Access. Medscape: Medscape Access. Retrieved April 3, 2011, from http://www.medscape.org/viewarticle/704202_2 Zambon, A., Polo Friz, H., Contiero, P., & Corrao, G. (2009). Effect of macrolide and fluoroquinolone antibacterials on the risk of ventricular arrhythmia and cardiac arrest: an observational study in Italy using case-control, case-crossover and case-time-control designs. Drug Safety, 32(2), 159-167. Retrieved from EBSCOhost Zimetbaum, P., & Josephson, M. (1999, February 3). Risk factors for and diagnosis of long QT and torsades de pointes. Risk factors of and diagnosis of long QT and torsades de pointes. Retrieved April 4, 2011, from http://cmbi.bjmu.edu.cn/uptodate/cardiac%20arrhythmias/Diagnosis/Risk%20factors%20for%20and%20diagnosis%20of%20the%20long%20QT%20syndrome%20and%20torsade%20de%20pointes.htm