Impact of Enteral Methadone on the Ability to Wean off Continuously Infused Opioids in Critically Ill,Mechanically Ventilated Adults: A Case-Control Study

Abstract

Spanish

French

BACKGROUND:

Continuously infused opioids are frequently used to optimize patient comfort in the intensive care unit (ICU). However, concerns about rebound pain and opioid withdrawal may delay efforts to discontinue this therapy.

OBJECTIVE:

To measure the association between use of scheduled enteral methadone according to a protocol in mechanically ventilated, medical critically ill adults receiving prolonged continuously infused fentanyl and the time to discontinue continuously infused fentanyl therapy.

METHODS:

This case-control study included 20 consecutive mechanically ventilated adults in a medical ICU, without a history of chronic opioid use, who received 72 or more hours of continuously infused fentanyl and were prescribed scheduled enteral methadone as part of a protocol medical ICU strategy to wean off continuously infused fentanyl. Patients were matched in a 1:2 fashion, by duration of mechanical ventilation, to 40 consecutive preprotocol medical ICU patients meeting the same criteria but who were never given methadone. Duration of continuously infused fentanyl was compared between the 2 groups by constructing Kaplan-Meier plots and estimating the likelihood that methadone use was associated with a decrease in continuously infused fentanyl requirements over time, using a Cox proportional hazards model.

RESULTS:

The groups were well matched except the methadone patients were older (p = 0.04). Time (median [interquartile range]) to continuously infused fentanyl discontinuation was shorter in the methadone group (4.5 [3.9-5.8] vs 7.0 [4.9-11.5] days; p = 0.002). Continuously infused fentanyl was more likely to be discontinued 2 days after methadone was first initiated (hazard ratio 9.1; p = 0.0004). The proportion of patients who experienced 1 or more episodes of either QTc interval prolongation (p = 0.79) or unarousability (p = 0.47) was similar between the groups.

CONCLUSIONS:

Enterally administered methadone is associated with earlier cessation of continuously infused fentanyl in mechanically ventilated adults without a history of opioid dependence admitted to a medical ICU. Prospective, controlled studies are needed to further evaluate the safety and efficacy of methadone as a strategy to wean off continuously infused fentanyl in different ICU populations.

Keywords

analgesic critical care fentanyl mechanical ventilation methadone opioid withdrawal

Get full access to this article

View all access options for this article.

References

Jacobi

, Fraser

, Coursin

, et al. Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult. Crit Care Med 2002; 30: 119–41.

Wunsch

, Kahn

, Kramer

, Rubenfeld

. Use of intravenous infusion sedation among mechanically ventilated patients in the United States. Crit Care Med 2009; 37: 3031–9.

Erstad

, Puntillo

, Gilbert

, et al. Pain management principles in the critically ill. Chest 2009; 135: 1075–86.

Strom

, Martinussen

, Toft

. A protocol of no sedation for critically ill patients receiving mechanical ventilation: a randomised trial. Lancet 2010; 375: 475–80.

Wøien

, Stubhaug

, Bjørk

. Analgesia and sedation of mechanically ventilated patients: a national survey of clinical practice. Acta Anaesthesiol Scand 2012; 56: 23–9.

Patel

, Kress

. Sedation and analgesia in the mechanically ventilated patient. Am J Respir Crit Care Med 2012; 185: 486–97.

Olafson

, Ramsey

, Ariano

, et al. Sedation and analgesia usage in severe pandemic H1N1 (2009) infection: a comparison to respiratory failure secondary to other infectious pneumonias. Ann Pharmacother 2012; 46: 9–20. DOI: 10.1345/aph.1Q446

Devlin

, Roberts

. Pharmacology of commonly used sedatives and analgesics in the ICU. Crit Care Clin 2009; 25: 431–49.

Cammarano

, Pittet

, Weitz

, Schlobohm

, Marks

. Acute withdrawal syndrome related to the administration of analgesic and sedative medications in adult intensive care unit patients. Crit Care Med 1998; 26: 676–84.

10.

Girard

, Kress

, Fuchs

, et al. Efficacy and safety of a paired sedation and ventilator weaning protocol for mechanically ventilated patients in intensive care (Awakening and Breathing Controlled trial): a randomised controlled trial. Lancet 2008; 371: 126–34.

11.

Robertson

, Darsey

, Fortenberry

, Pettignano

, Hartley

. Evaluation of an opiate-weaning protocol using methadone in pediatric intensive care unit patients. Pediatr Crit Care Med 2000; 1: 119–123.

12.

Meyer

, Berens

. Efficacy of an enteral 10-day methadone wean to prevent opioid withdrawal in fentanyl-tolerant pediatric intensive care unit patients. Pediatr Crit Care Med 2001; 2: 329–33.

13.

Bowens

, Thompson

, Breitzka

, Thompson

, Sheeran

. A trial of methadone tapering schedules in pediatric intensive care unit patients exposed to prolonged sedative infusions. Pediatr Crit Care Med 2011; 12: 504–11.

14.

Lugo

, MacLaren

, Cash

, Pribble

, Vernon

. Enteral methadone to expedite fentanyl discontinuation and prevent opioid abstinence syndrome in the PICU. Pharmacotherapy 2001; 21: 1566–73.

15.

Durand

, Alhammad

, Willett

. Practical consideration for optimal transdermal drug delivery. Am J Health Syst Pharm 2012; 69: 116–24.

16.

Cigada

, Pezzi

, Di Mauro

, et al. Sedation in the critically ill ventilated patient: possible role of enteral drugs. Intensive Care Med 2005; 31: 482–6.

17.

Gesin

, Kane-Gill

, Dasta

, Birrer

, Kolnik

, Cheatham

. Diazepam as a component of goal-directed sedation in critically ill trauma patients. J Crit Care 2011; 26: 122–6. DOI: 10.1016/j.jcrc.2010.09.008

18.

Package insert. Methadose (methadone hydrochloride). Hazelwood, MO: Mallinckrodt Inc., May 2009.

19.

Lugo

, Satterfield

, Kern

. Pharmacokinetics of methadone. J Pain Palliat Care Pharmacother 2005; 19: 13–24.

20.

Mao

, Price

, Lu

, Mayer

. Antinociceptive tolerance to the muopioid agonist DAMGO is dose-dependently reduced by MK-801 in rats. Neurosci Lett 1998; 250: 193–6.

21.

Trujillo

, Akil

. Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801. Science 1991; 251: 85–7.

22.

Pergolizzi

, Boger

, Budd

, et al. Opioids and the management of chronic severe pain in the elderly: consensus statement of an International Expert Panel with focus on the six clinically most often used World Health Organization step III opioids (buprenorphine, fentanyl, hydromorphone, methadone, morphine, oxycodone). Pain Pract 2008; 8: 287–313.

23.

Devlin

, Mallow-Corbett

, Riker

. Adverse drug events associated with the use of analgesics, sedatives, and antipsychotics in the intensive care unit. Crit Care Med 2010; 38 (6 suppl): S231–43.

24.

Kher

, Roberts

, Garpestad

, et al. Development, implementation and evaluation of an institutional daily awakening and spontaneous breathing trial protocol: a process improvement project. J Intensive Care Med 2012 (in press).

25.

Patanwala

, Duby

, Waters

, Erstad

. Opioid conversions in acute care. Ann Pharmacother 2007; 41: 255–66. DOI: 10.1345/aph.1H421

26.

Riker

, Picard

, Fraser

. Prospective evaluation of the Sedation-Agitation Scale for adult critically ill patients. Crit Care Med 1999; 27: 1325–9.

27.

Drew

, Ackerman

, Funk

, et al. Prevention of torsades de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology foundation. Circulation 2010; 121: 1047–60.

28.

Devlin

, Roberts

, Fong

, et al. Efficacy and safety of quetiapine for delirium in the ICU: a randomized, double-blind, placebo-controlled pilot study. Crit Care Med 2010; 38: 419–27.

29.

Berens

, Meyer

, Mikhailov

, et al. A prospective evaluation of opioid weaning in opioid-dependent pediatric critical care patients. Anesth Analg 2006; 102: 1045–50.

30.

Dive

, Moulart

, Jonard

, Jamart

, Mahieu

. Gastroduodenal motility in mechanically ventilated critically ill patients: a manometric study. Crit Care Med 1994; 22: 441–7.

31.

Pickham

, Helfenbein

, Shinn

, et al. High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in Practice (QTIP) Study. Crit Care Med 2012; 40: 394–9.

32.

Scholz

, Steinfath

, Schulz

. Clinical pharmacokinetics of alfentanil, fentanyl and sufentanil: an update. Clin Pharmacokinet 1996; 31: 275–92.