Clinical trial NCT04398316: High Dose IV Lidocaine vs Hydromorphone for Abdominal Pain in the Emergency Department
Official title: High Dose Intravenous Lidocaine vs Hydromorphone for Acute Abdominal Pain in the Emergency Department: A Randomized, Comparative Efficacy Trial
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Abdominal Pain
Renal Colic
Keywords: lidocaine
hydromorphone
abdominal pain
Lead sponsor: Hennepin Healthcare Research Institute
Sponsor class: OTHER
First posted: 2020-05-21
Enrollment: 4
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Intravenous lidocaine will be given at a dose of 2 mg/kg intravenously to patients in the emergency department with a diagnosis of acute abdominal pain. Its efficacy will be compared to 1 mg of intravenous hydromorphone, with a primary endpoint of mean improvement of pain at 90 minutes.

Detailed description: Abdominal pain is a common chief complaint for patients presenting to the emergency department (ED) in the United States. Intravenous opioids are commonly used to treat acute abdominal pain in the ED. These medications are highly efficacious and, when used in a monitored setting such as the ED, extremely safe. Use of opioids has fallen out of favor because of a spike in opioid-related overdose deaths throughout the United States. While use of opioids in the ED is unlikely to contribute to outpatient opioid deaths, minimizing the use of opioids in the ED will contribute to an opioid free culture, in which opioids are used only when absolutely necessary. A variety of different types of medications can be used in lieu of opioids. One such medication, intravenous lidocaine, has been used extensively for neuropathic pain, in the peri- and post-operative surgical setting, the cardiac care unit, and most recently in the emergency department.

Intravenous lidocaine has long been used to treat pain. In publications dating back to 1980, intravenous lidocaine has been shown to be an effective treatment for neuropathic pain. In the postoperative setting, intravenous lidocaine decreased pain and decreased the need for opiates. More recently, emergency medicine investigators in Iran demonstrated that intravenous lidocaine decreased pain associated with renal colic and limb ischemia. An ED-based study in the United States showed comparable efficacy between morphine and intravenous lidocaine when used for acute pain. Most recently, a prospective RCT showed 120 mg of intravenous lidocaine was efficacious for abdominal pain, albeit not as effective as 1 mg of hydromorphone. However, a subgroup analysis showed that when lidocaine was dosed at 2 mg/kg, it was equally as effective as hydromorphone.

Over the years, intravenous lidocaine has been used for a variety of indications including arrhythmia prophylaxis in patients with acute coronary syndromes. Known side effects of intravenous lidocaine range from transient neurological symptoms (dizziness, paresthesias), to cardiac dysrhythmias and seizure. To date, no deaths have been attributed to its use for treating pain, and the only documented significant complication was due to an unintentional overdose when a patient received ten times the normal dose. All reported side effects in pain patients have been transient and resolved by either stopping the drug, decreasing the infusion rate or by observation alone. Additionally, doses of 2 mg/kg have been tolerated well in the outpatient setting, operating room and ED without any serious side effects. Thus, intravenous lidocaine is an emerging medication for safe and rapid relief of pain, has no known addictive properties, and creates a potential for a pain practice paradigm shift in the United States.

We therefore propose a randomized, double blind, comparative efficacy trial to address the following aim:

To determine if a 2 mg/kg dose of intravenous lidocaine is as equally efficacious as a single dose of 1 mg intravenous hydromorphone for acute abdominal pain in the emergency department.

Eligibility criteria: Inclusion Criteria:

* Must be a patient in the emergency department (ED)
* Must have acute abdominal pain, defined as abdominal or flank pain of a duration of 7 days or less
* Predicted treatment must include the use of an intravenous opiate

Exclusion Criteria:

* Cardiac conduction system impairment (QTc duration \> 0.5s, QRS duration \> 0.12s, PR interval \<0.12s or \> 0.2s)
* Known renal (CKD \>2) or liver disease (Childs-Pugh B or greater)
* Hemodynamically instability, defined by the attending physician
* Pregnant or breastfeeding
* Have a known allergy to either medication
* Used of prescription or illicit opioids within the previous week
* Patients with a chronic pain disorder, defined as use of any analgesic medication on more days than not during the four weeks preceding the acute episode of pain

Primary outcomes:
measure: Mean Improvement in Pain at 90 Minutes
timeFrame: 90 minutes
Secondary outcomes:
measure: Sufficient Pain Relief
timeFrame: From administration of study drug until patient leaves the emergency department, up until 3 hours from administration of study drug.
measure: Improvement in Numerical Pain Score at 15 Minutes
timeFrame: 15 minutes
measure: Improvement in Numerical Pain Score at 30 Minutes
timeFrame: 30 minutes
measure: Improvement in Numerical Pain Score at 60 Minutes
timeFrame: 60 minutes
measure: Improvement in Numerical Pain Score at 120 Minutes
timeFrame: 120 minutes
measure: Improvement in Numerical Pain Score at 150 Minutes
timeFrame: 150 minutes
measure: Improvement in Numerical Pain Score at 180 Minutes
timeFrame: 180 minutes
measure: Patient Preference for the Medication They Received
timeFrame: Day 7
measure: Side Effects
timeFrame: 15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes, 180 minutes and at 7 days
measure: Medication for Side Effects
timeFrame: 15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and 180 minutes
measure: Administration of Naloxone
timeFrame: 15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and at 180 minutes
measure: Change in Disposition
timeFrame: 15 minutes after administration of study drug then again at 30 minutes, 60 minutes, 90 minutes, 120 minutes, 150 minutes and at 180 minutes
measure: Missed Diagnosis
timeFrame: 7 days after administration of study drug
measure: Serious Adverse Event
timeFrame: 180 minutes after administration of study drug
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Hennepin County Medical Center
state: Minnesota
Study officials:
affiliation: Hennepin County Medical Center, Minneapolis
name: Elliott Chinn, DO
role: PRINCIPAL_INVESTIGATOR
References:
citation: Tremont-Lukats IW, Challapalli V, McNicol ED, Lau J, Carr DB. Systemic administration of local anesthetics to relieve neuropathic pain: a systematic review and meta-analysis. Anesth Analg. 2005 Dec;101(6):1738-1749. doi: 10.1213/01.ANE.0000186348.86792.38.
citation: Kranke P, Jokinen J, Pace NL, Schnabel A, Hollmann MW, Hahnenkamp K, Eberhart LH, Poepping DM, Weibel S. Continuous intravenous perioperative lidocaine infusion for postoperative pain and recovery. Cochrane Database Syst Rev. 2015 Jul 16;(7):CD009642. doi: 10.1002/14651858.CD009642.pub2.
citation: Ventham NT, Kennedy ED, Brady RR, Paterson HM, Speake D, Foo I, Fearon KC. Efficacy of Intravenous Lidocaine for Postoperative Analgesia Following Laparoscopic Surgery: A Meta-Analysis. World J Surg. 2015 Sep;39(9):2220-34. doi: 10.1007/s00268-015-3105-6.
citation: Sun Y, Li T, Wang N, Yun Y, Gan TJ. Perioperative systemic lidocaine for postoperative analgesia and recovery after abdominal surgery: a meta-analysis of randomized controlled trials. Dis Colon Rectum. 2012 Nov;55(11):1183-94. doi: 10.1097/DCR.0b013e318259bcd8.
citation: Vigneault L, Turgeon AF, Cote D, Lauzier F, Zarychanski R, Moore L, McIntyre LA, Nicole PC, Fergusson DA. Perioperative intravenous lidocaine infusion for postoperative pain control: a meta-analysis of randomized controlled trials. Can J Anaesth. 2011 Jan;58(1):22-37. doi: 10.1007/s12630-010-9407-0.
citation: Marret E, Rolin M, Beaussier M, Bonnet F. Meta-analysis of intravenous lidocaine and postoperative recovery after abdominal surgery. Br J Surg. 2008 Nov;95(11):1331-8. doi: 10.1002/bjs.6375.
citation: Fitzpatrick BM, Mullins ME. Intravenous lidocaine for the treatment of acute pain in the emergency department. Clin Exp Emerg Med. 2016 Jun 30;3(2):105-108. doi: 10.15441/ceem.15.103. eCollection 2016 Jun.
citation: Soleimanpour H, Hassanzadeh K, Mohammadi DA, Vaezi H, Esfanjani RM. Parenteral lidocaine for treatment of intractable renal colic: a case series. J Med Case Rep. 2011 Jun 29;5:256. doi: 10.1186/1752-1947-5-256.
citation: Soleimanpour H, Hassanzadeh K, Vaezi H, Golzari SE, Esfanjani RM, Soleimanpour M. Effectiveness of intravenous lidocaine versus intravenous morphine for patients with renal colic in the emergency department. BMC Urol. 2012 May 4;12:13. doi: 10.1186/1471-2490-12-13.
citation: Firouzian A, Alipour A, Rashidian Dezfouli H, Zamani Kiasari A, Gholipour Baradari A, Emami Zeydi A, Amini Ahidashti H, Montazami M, Hosseininejad SM, Yazdani Kochuei F. Does lidocaine as an adjuvant to morphine improve pain relief in patients presenting to the ED with acute renal colic? A double-blind, randomized controlled trial. Am J Emerg Med. 2016 Mar;34(3):443-8. doi: 10.1016/j.ajem.2015.11.062. Epub 2015 Dec 1.
citation: Vahidi E, Shakoor D, Aghaie Meybodi M, Saeedi M. Comparison of intravenous lidocaine versus morphine in alleviating pain in patients with critical limb ischaemia. Emerg Med J. 2015 Jul;32(7):516-9. doi: 10.1136/emermed-2014-203944. Epub 2014 Aug 21.
citation: Clattenburg EJ, Nguyen A, Yoo T, Flores S, Hailozian C, Louie D, Herring AA. Intravenous Lidocaine Provides Similar Analgesia to Intravenous Morphine for Undifferentiated Severe Pain in the Emergency Department: A Pilot, Unblinded Randomized Controlled Trial. Pain Med. 2019 Apr 1;20(4):834-839. doi: 10.1093/pm/pny031.
citation: Chinn E, Friedman BW, Naeem F, Irizarry E, Afrifa F, Zias E, Jones MP, Pearlman S, Chertoff A, Wollowitz A, Gallagher EJ. Randomized Trial of Intravenous Lidocaine Versus Hydromorphone for Acute Abdominal Pain in the Emergency Department. Ann Emerg Med. 2019 Aug;74(2):233-240. doi: 10.1016/j.annemergmed.2019.01.021. Epub 2019 Feb 26.